2024-03-29T09:38:43Zhttp://oai-repositori.upf.edu/oai/requestoai:repositori.upf.edu:10230/213202018-01-24T08:25:35Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Derelle, Romain
author
Kondrashov, Fyodor A., 1979-
author
Arkhipov, Vladimir Y.
author
Corbel, Hélène
author
Frantz, Adrien
author
Gasparini, Julien
author
Jacquin, Lisa
author
Jacob, Gwenaël
author
Thibault, Sophie
author
Baudry, Emmanuelle
author
2013
Genetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in many birds. Feral pigeons (Columba livia) show two major melanin-based colorations: a red coloration due to pheomelanic pigment and a black coloration due to eumelanic pigment. Furthermore, within each color type, feral pigeons display continuous variation in the amount of melanin pigment present in the feathers, with individuals varying from pure white to a full dark melanic color. Coloration is highly heritable and it has been suggested that it is under natural or sexual selection, or both. Our objective was to investigate whether MC1R allelic variants are associated with plumage color in feral pigeons./n/nWe sequenced 888 bp of the coding sequence of MC1R among pigeons varying both in the type, eumelanin or pheomelanin, and the amount of melanin in their feathers. We detected 10 non-synonymous substitutions and 2 synonymous substitution but none of them were associated with a plumage type. It remains possible that non-synonymous substitutions that influence coloration are present in the short MC1R fragment that we did not sequence but this seems unlikely because we analyzed the entire functionally important region of the gene./nOur results show that color differences among feral pigeons are probably not attributable to amino acid variation at the MC1R locus. Therefore, variation in regulatory regions of MC1R or variation in other genes may be responsible for the color polymorphism of feral pigeons.
Derelle R, Kondrashov FA, Arkhipov VY, Corbel H, Frantz A, Gasparini J, et al. Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene (MC1R). BMC Res. Notes. 2013; 6(1): 310. DOI: 10.1186/1756-0500-6-310
1756-0500
http://hdl.handle.net/10230/21320
http://dx.doi.org/10.1186/1756-0500-6-310
Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene (MC1R)
oai:repositori.upf.edu:10230/222282021-06-08T08:59:55Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Noort, Vera van
author
Seebacher, Jan
author
Bader, Samuel
author
Mohammed, Shabaz
author
Vonkova, Ivana
author
Betts, Matthew J.
author
Kühner, Sebastian
author
Kumar, Runjun
author
Maier, Tobias
author
O'Flaherty, Martina
author
Rybin, Vladimir
author
Schmeisky, Arne
author
Yus, Eva
author
Stülke, Jörg
author
Serrano Pubull, Luis, 1982-
author
Russell, Robert B.
author
Heck, Albert J.R.
author
Bork, Peer
author
Gavin, Anne-Claude
author
2012
Protein post-translational modifications (PTMs) represent important regulatory states that when combined have been hypothesized to act as molecular codes and to generate a functional diversity beyond genome and transcriptome. We systematically investigate the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein-specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes. Reciprocally, deletion of the two putative N-acetyltransferases affects protein phosphorylation, confirming cross-talk between the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome revealed that both PTMs are very common, that (as in Eukaryotes) they often co-occur within the same protein and that they are frequently observed at interaction interfaces and in multifunctional proteins. The results imply previously unreported hidden layers of post-transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell.
van Noort V, Seebacher J, Bader S, Mohammed S, Vonkova I, Betts MJ et al. Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium. Mol Syst Biol. 2012; 8: 571. DOI: 10.1038/msb.2012.4
1744-4292
http://hdl.handle.net/10230/22228
http://dx.doi.org/10.1038/msb.2012.4
Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium
oai:repositori.upf.edu:10230/222292023-07-07T12:19:38Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Yus, Eva
author
Güell Cargol, Marc, 1982-
author
Vivancos Prellezo, Ana
author
Chen, Wei-Hua
author
Lluch-Senar, Maria 1982-
author
Delgado Blanco, Javier
author
Gavin, Anne-Claude
author
Bork, Peer
author
Serrano Pubull, Luis, 1982-
author
2012
Here, we report the genome-wide identification of small RNAs associated with transcription start sites (TSSs), termed tssRNAs, in Mycoplasma pneumoniae. tssRNAs were also found to be present in a different bacterial phyla, Escherichia coli. Similar to the recently identified promoter-associated tiny RNAs (tiRNAs) in eukaryotes, tssRNAs are associated with active promoters. Evidence suggests that these tssRNAs are distinct from previously described abortive transcription RNAs. ssRNAs have an average size of 45 bases and map exactly to the beginning of cognate full-length transcripts and to cryptic TSSs. Expression of bacterial tssRNAs requires factors other than the standard RNA polymerase holoenzyme. We have found that the RNA polymerase is halted at tssRNA positions in vivo, which may indicate that a pausing mechanism exists to prevent transcription in the absence of genes. These results suggest that small RNAs associated with TSSs could be a universal feature of bacterial transcription.
Yus E, Güell M, Vivancos AP, Chen WH, Lluch-Senar M, Delgado J et al. Transcription start site associated RNAs in bacteria. Mol Syst Biol. 2012; 8:585. DOI: 10.1038/msb.2012.16
1744-4292
http://hdl.handle.net/10230/22229
http://dx.doi.org/10.1038/msb.2012.16
Transcription start site associated RNAs in bacteria
oai:repositori.upf.edu:10230/222302021-04-12T09:23:38Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Wodke, Judith A.H.
author
Puchalka, Jacek
author
Lluch-Senar, Maria 1982-
author
Marcos del Águila, Josep, 1971-
author
Yus, Eva
author
Godinho, Miguel
author
Gutiérrez Gallego, Ricardo, 1968-
author
Martins dos Santos, Vitor
author
Serrano Pubull, Luis, 1982-
author
Klipp, E., 1965-
author
Maier, Tobias
author
2013
Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model organism for bacterial systems biology for which substantial experimental information is available. With the goal of understanding the complex interactions underlying its metabolism, we analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different omics analyses under a range of conditions into a constraint-based model backbone. Iterating model predictions, hypothesis generation, experimental testing, and model refinement, we accurately curated the network and quantitatively explored the energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its energy for maintenance tasks instead of growth. We show that in highly linear networks the prediction of flux distributions for different growth times allows analysis of time-dependent changes, albeit using a static model. By performing an in silico knock-out study as well as analyzing flux distributions in single and double mutant phenotypes, we demonstrated that the model accurately represents the metabolism of M. pneumoniae. The experimentally validated model provides a solid basis for understanding its metabolic regulatory mechanisms.
Wodke JA, Puchałka J, Lluch-Senar M, Marcos J, Yus E, Godinho M et al. Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale metabolic modeling. Mol Syst Biol. 2013; 9: 653. DOI: 10.1038/msb.2013.6
1744-4292
http://hdl.handle.net/10230/22230
http://dx.doi.org/10.1038/msb.2013.6
Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale metabolic modeling
oai:repositori.upf.edu:10230/222312021-04-12T09:38:30Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Lluch-Senar, Maria 1982-
author
Luong, Khai
author
Lloréns Rico, Verónica, 1989-
author
Delgado Blanco, Javier
author
Fang, Gang
author
Spittle, Kristi
author
Clark, Tyson A.
author
Schadt, Eric
author
Turner, Stephen W.
author
Korlach, Jonas
author
Serrano Pubull, Luis, 1982-
author
2013
In the bacterial world, methylation is most commonly associated with restriction-modification systems that provide a defense mechanism against invading foreign genomes. In addition, it is known that methylation plays functionally important roles, including timing of DNA replication, chromosome partitioning, DNA repair, and regulation of gene expression. However, full DNA methylome analyses are scarce due to a lack of a simple methodology for rapid and sensitive detection of common epigenetic marks (ie N(6)-methyladenine (6 mA) and N(4)-methylcytosine (4 mC)), in these organisms. Here, we use Single-Molecule Real-Time (SMRT) sequencing to determine the methylomes of two related human pathogen species, Mycoplasma genitalium G-37 and Mycoplasma pneumoniae M129, with single-base resolution. Our analysis identified two new methylation motifs not previously described in bacteria: a widespread 6 mA methylation motif common to both bacteria (5'-CTAT-3'), as well as a more complex Type I m6A sequence motif in M. pneumoniae (5'-GAN(7)TAY-3'/3'-CTN(7)ATR-5'). We identify the methyltransferase responsible for the common motif and suggest the one involved in M. pneumoniae only. Analysis of the distribution of methylation sites across the genome of M. pneumoniae suggests a potential role for methylation in regulating the cell cycle, as well as in regulation of gene expression. To our knowledge, this is one of the first direct methylome profiling studies with single-base resolution from a bacterial organism.
Lluch-Senar M, Luong K, Lloréns-Rico V, Delgado J, Fang G, Spittle K et al. Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution. PLoS Genet. 2013; 9(1): e1003191. DOI: 10.1371/journal.pgen.1003191
1553-7390
http://hdl.handle.net/10230/22231
http://dx.doi.org/10.1371/journal.pgen.1003191
Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution
oai:repositori.upf.edu:10230/222322021-04-12T09:39:32Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Simões Correia, Joana
author
Figueiredo, Joana
author
Lopes, Rui
author
Stricher, François
author
Oliveira, Carla
author
Serrano Pubull, Luis, 1982-
author
Seruca, Raquel
author
2012
E-cadherin is critical for the maintenance of tissue architecture due to its role in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary Diffuse Gastric Cancer (HDGC) and missense mutations represent a clinical burden, due to the uncertainty of their pathogenic role. In vitro and in vivo, most mutations lead to loss-of-function, although the causal factor is unknown for the majority. We hypothesized that destabilization could account for the pathogenicity of E-cadherin missense mutations in HDGC, and tested our hypothesis using in silico and in vitro tools. FoldX algorithm was used to calculate the impact of each mutation in E-cadherin native-state stability, and the analysis was complemented with evolutionary conservation, by SIFT. Interestingly, HDGC patients harbouring germline E-cadherin destabilizing mutants present a younger age at diagnosis or death, suggesting that the loss of native-state stability of E-cadherin accounts for the disease phenotype. To elucidate the biological relevance of E-cadherin destabilization in HDGC, we investigated a group of newly identified HDGC-associated mutations (E185V, S232C and L583R), of which L583R is predicted to be destabilizing. We show that this mutation is not functional in vitro, exhibits shorter half-life and is unable to mature, due to premature proteasome-dependent degradation, a phenotype reverted by stabilization with the artificial mutation L583I (structurally tolerated). Herein we report E-cadherin structural models suitable to predict the impact of the majority of cancer-associated missense mutations and we show that E-cadherin destabilization leads to loss-of-function in vitro and increased pathogenicity in vivo.
Simões-Correia J, Figueiredo J, Lopes R, Stricher F, Oliveira C, Serrano L et al. E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer. PLoS One. 2012; 7(3): e33783. DOI: 10.1371/journal.pone.0033783
1932-6203
http://hdl.handle.net/10230/22232
http://dx.doi.org/10.1371/journal.pone.0033783
E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer
oai:repositori.upf.edu:10230/222332021-06-08T09:15:11Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Dos Santos, Helena G.
author
Abia, David
author
Janowski, Robert
author
Mortuza, Gulnahar
author
Bertero, Michela G.
author
Boutin, Maïlys
author
Guarín, Nayibe
author
Méndez Giraldez, Raúl
author
Nuñez, Alfonso
author
Pedrero, Juan G.
author
Redondo, Pilar
author
Sanz, María
author
Speroni, Silvia
author
Teichert, Florian
author
Bruix, Maria
author
Carazo, José M.
author
González, Cayetano
author
Reina, José
author
Valpuesta, José M.
author
Vernos, Isabelle, 1959-
author
Zabala, Juan C.
author
Montoya, Guillermo
author
Coll, Miquel
author
Bastolla, Ugo
author
Serrano Pubull, Luis, 1982-
author
2013
Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php.
Dos Santos HG, Abia D, Janowski R, Mortuza G, Bertero MG, Boutin M et al. Structure and non-structure of centrosomal proteins. PLoS One. 2013; 8(5): e62633. DOI: 10.1371/journal.pone.0062633
1932-6203
http://hdl.handle.net/10230/22233
http://dx.doi.org/10.1371/journal.pone.0062633
Structure and non-structure of centrosomal proteins
oai:repositori.upf.edu:10230/224742021-04-12T09:53:19Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Curwin, Amy
author
Blume, Julia von
author
Malhotra, Vivek
author
2012
The mechanism of cargo sorting at the trans-Golgi network (TGN) for secretion is poorly understood. We previously reported the involvement of the actin-severing protein cofilin and the Ca(2+) ATPase secretory pathway calcium ATPase 1 (SPCA1) in the sorting of soluble secretory cargo at the TGN in mammalian cells. Now we report that cofilin in yeast is required for export of selective secretory cargo at the late Golgi membranes. In cofilin mutant (cof1-8) cells, the cell wall protein Bgl2 was secreted at a reduced rate and retained in a late Golgi compartment, whereas the plasma membrane H(+) ATPase Pma1, which is transported in the same class of carriers, reached the cell surface. In addition, sorting of carboxypeptidase Y (CPY) to the vacuole was delayed, and CPY was secreted from cof1-8 cells. Loss of the yeast orthologue of SPCA1 (Pmr1) exhibited similar sorting defects and displayed synthetic sickness with cof1-8. In addition, overexpression of PMR1 restored Bgl2 secretion in cof1-8 cells. These findings highlight the conserved role of cofilin and SPCA1/Pmr1 in sorting of the soluble secretory proteins at the TGN/late Golgi membranes in eukaryotes.
Curwin AJ, von Blume J, Malhotra V. Cofilin-mediated sorting and export of specific cargo from the Golgi apparatus in yeast. Mol Biol Cell. 2012; 23(12): 2327-38. DOI: 10.1091/mbc.E11-09-0826
1059-1524
http://hdl.handle.net/10230/22474
http://dx.doi.org/10.1091/mbc.E11-09-0826
Cofilin-mediated sorting and export of specific cargo from the Golgi apparatus in yeast
oai:repositori.upf.edu:10230/224752020-06-15T11:37:00Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Blume, Julia von
author
Alleaume, Anne-Marie
author
Kienzle, Christine
author
Carreras Sureda, Amado, 1986-
author
Valverde, M. A. (Miguel Ángel), 1963-
author
Malhotra, Vivek
author
2012
Ca(2+) import into the lumen of the trans-Golgi network (TGN) by the secretory pathway calcium ATPase1 (SPCA1) is required for the sorting of secretory cargo. How is Ca(2+) retained in the lumen of the Golgi, and what is its role in cargo sorting? We show here that a soluble, lumenal Golgi resident protein, Cab45, is required for SPCA1-dependent Ca(2+) import into the TGN; it binds secretory cargo in a Ca(2+)-dependent reaction and is required for its sorting at the TGN.
von Blume J, Alleaume AM, Kienzle C, Carreras-Sureda A, Valverde M, Malhotra V. Cab45 is required for Ca(2+)-dependent secretory cargo sorting at the trans-Golgi network. J Cell Biol. 2012;199(7):1057-66. DOI: 10.1083/jcb.201207180
0021-9525
http://hdl.handle.net/10230/22475
http://dx.doi.org/10.1083/jcb.201207180
Cab45 is required for Ca(2+)-dependent secretory cargo sorting at the trans-Golgi network
oai:repositori.upf.edu:10230/224762020-06-15T11:40:20Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Mitrovic, Sandra
author
Nogueira, Cristina
author
Cantero Recasens, Gerard, 1984-
author
Kiefer, Kerstin, 1986-
author
Fernández-Fernández, José Manuel, 1967-
author
Popoff, Jean-François
author
Casano, Laetitia
author
Bard, Frederic A.
author
Gómez, Raul
author
Valverde, M. A. (Miguel Ángel), 1963-
author
Malhotra, Vivek
author
2013
Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca(2+)-activated channel TRPM5, for MUC5AC secretion. TRPM5 was required for PMA and ATP-induced secretion of MUC5AC from the post-Golgi secretory granules. Stable knockdown of TRPM5 reduced a TRPM5-like current and ATP-mediated Ca(2+) signal. ATP-induced MUC5AC secretion depended strongly on Ca(2+) influx, which was markedly reduced in TRPM5 knockdown cells. The difference in ATP-induced Ca(2+) entry between control and TRPM5 knockdown cells was abrogated in the absence of extracellular Ca(2+) and by inhibition of the Na(+)/Ca(2+) exchanger (NCX). Accordingly, MUC5AC secretion was reduced by inhibition of NCX. Thus TRPM5 activation by ATP couples TRPM5-mediated Na(+) entry to promote Ca(2+) uptake via an NCX to trigger MUC5AC secretion
Mitrovic S, Nogueira C, Cantero-Recasens G, Kiefer K, Fernández-Fernández JM, Popoff JF et al. TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. Elife. 2013;2:e00658. DOI: 10.7554/eLife.00658
2050-084X
http://hdl.handle.net/10230/22476
http://dx.doi.org/10.7554/eLife.00658
TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells
oai:repositori.upf.edu:10230/224772023-09-26T07:54:00Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Wakana, Yuichi
author
Villeneuve, Julien
author
Galen, Josse van
author
Cruz-Garcia, David
author
Tagaya, Mitsuo
author
Malhotra, Vivek
author
2013
Here we report that the kinesin-5 motor Klp61F, which is known for its role in bipolar spindle formation in mitosis, is required for protein transport from the Golgi complex to the cell surface in Drosophila S2 cells. Disrupting the function of its mammalian orthologue, Eg5, in HeLa cells inhibited secretion of a protein called pancreatic adenocarcinoma up-regulated factor (PAUF) but, surprisingly, not the trafficking of vesicular stomatitis virus G protein (VSV-G) to the cell surface. We have previously reported that PAUF is transported from the trans-Golgi network (TGN) to the cell surface in specific carriers called CARTS that exclude VSV-G. Inhibition of Eg5 function did not affect the biogenesis of CARTS; however, their migration was delayed and they accumulated near the Golgi complex. Altogether, our findings reveal a surprising new role of Eg5 in nonmitotic cells in the facilitation of the transport of specific carriers, CARTS, from the TGN to the cell surface.
Wakana Y, Villeneuve J, van Galen J, Cruz-Garcia D, Tagaya M, Malhotra V. Kinesin-5/Eg5 is important for transport of CARTS from the trans-Golgi network to the cell surface. J Cell Biol. 2013;202(2):241-50. DOI: 10.1083/jcb.201303163
0021-9525
http://hdl.handle.net/10230/22477
http://dx.doi.org/10.1083/jcb.201303163
Kinesin-5/Eg5 is important for transport of CARTS from the trans-Golgi network to the cell surface
oai:repositori.upf.edu:10230/224782020-06-15T11:47:14Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Ferreira, Pedro G.
author
Patalano, Solenn
author
Chauhan, Ritika
author
Ffrench-Constant, Richard
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Guigó Serra, Roderic
author
Sumner, Seirian
author
2013
BACKGROUND: Understanding how alternative phenotypes arise from the same genome is a major challenge in modern biology. Eusociality in insects requires the evolution of two alternative phenotypes - workers, who sacrifice personal reproduction, and queens, who realize that reproduction. Extensive work on honeybees and ants has revealed the molecular basis of derived queen and worker phenotypes in highly eusocial lineages, but we lack equivalent deep-level analyses of wasps and of primitively eusocial species, the latter of which can reveal how phenotypic decoupling first occurs in the early stages of eusocial evolution. RESULTS: We sequenced 20 Gbp of transcriptomes derived from brains of different behavioral castes of the primitively eusocial tropical paper wasp Polistes canadensis. Surprisingly, 75% of the 2,442 genes differentially expressed between phenotypes were novel, having no significant homology with described sequences. Moreover, 90% of these novel genes were significantly upregulated in workers relative to queens. Differential expression of novel genes in the early stages of sociality may be important in facilitating the evolution of worker behavioral complexity in eusocial evolution. We also found surprisingly low correlation in the identity and direction of expression of differentially expressed genes across similar phenotypes in different social lineages, supporting the idea that social evolution in different lineages requires substantial de novo rewiring of molecular pathways. CONCLUSIONS: These genomic resources for aculeate wasps and first transcriptome-wide insights into the origin of castes bring us closer to a more general understanding of eusocial evolution and how phenotypic diversity arises from the same genome.
Ferreira PG, Patalano S, Chauhan R, Ffrench-Constant R, Gabaldón T, Guigó R et al. Transcriptome analyses of primitively eusocial wasps reveal novel insights into the evolution of sociality and the origin of alternative phenotypes. Genome Biol. 2013;14(2):R20. DOI: 10.1186/gb-2013-14-2-r20
1465-6906
http://hdl.handle.net/10230/22478
http://dx.doi.org/10.1186/gb-2013-14-2-r20
Transcriptome analyses of primitively eusocial wasps reveal novel insights into the evolution of sociality and the origin of alternative phenotypes
oai:repositori.upf.edu:10230/224792020-06-15T11:49:55Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Hagen, Ferry
author
Ceresini, Paulo C.
author
Polacheck, Itzhack
author
Ma, Hansong
author
Nieuwerburgh, Filip van
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Kagan, Sarah
author
Pursall, E. Rhiannon
author
Hoogveld, Hans L.
author
Iersel, Leo J. van
author
Klau, Gunnar W.
author
Kelk, Steven M.
author
Stougie, Leen
author
Bartlett, Karen H.
author
Voelz, Kerstin
author
Pryszcz, Leszek Piotr, 1985-
author
Castañeda, Elizabeth
author
Lazera, Marcia
author
Meyer, Wieland
author
Deforce, Dieter
author
Meis, Jacques F.
author
May, Robin C.
author
Klaassen, Corné H. W.
author
Boekhout, Teun
author
2013
Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.
Hagen F, Ceresini PC, Polacheck I, Ma H, van Nieuwerburgh F, Gabaldón T et al. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest. PLoS One. 2013;8(8):e71148. DOI: 10.1371/journal.pone.0071148
1932-6203
http://hdl.handle.net/10230/22479
http://dx.doi.org/10.1371/journal.pone.0071148
Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest
oai:repositori.upf.edu:10230/224802020-06-15T11:54:33Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Traeger, Stefanie
author
Altegoer, Florian
author
Freitag, Michael
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Kempken, Frank
author
Kumar, Abhishek
author
Marcet Houben, Marina
author
Pöggeler, Stefanie
author
Stajich, Jason E.
author
Nowrousian, Minou
author
2013
Fungi are a large group of eukaryotes found in nearly all ecosystems. More than 250 fungal genomes have already been sequenced, greatly improving our understanding of fungal evolution, physiology, and development. However, for the Pezizomycetes, an early-diverging lineage of filamentous ascomycetes, there is so far only one genome available, namely that of the black truffle, Tuber melanosporum, a mycorrhizal species with unusual subterranean fruiting bodies. To help close the sequence gap among basal filamentous ascomycetes, and to allow conclusions about the evolution of fungal development, we sequenced the genome and assayed transcriptomes during development of Pyronema confluens, a saprobic Pezizomycete with a typical apothecium as fruiting body. With a size of 50 Mb and 13,400 protein-coding genes, the genome is more characteristic of higher filamentous ascomycetes than the large, repeat-rich truffle genome; however, some typical features are different in the P. confluens lineage, e.g. the genomic environment of the mating type genes that is conserved in higher filamentous ascomycetes, but only partly conserved in P. confluens. On the other hand, P. confluens has a full complement of fungal photoreceptors, and expression studies indicate that light perception might be similar to distantly related ascomycetes and, thus, represent a basic feature of filamentous ascomycetes. Analysis of spliced RNA-seq sequence reads allowed the detection of natural antisense transcripts for 281 genes. The P. confluens genome contains an unusually high number of predicted orphan genes, many of which are upregulated during sexual development, consistent with the idea of rapid evolution of sex-associated genes. Comparative transcriptomics identified the transcription factor gene pro44 that is upregulated during development in P. confluens and the Sordariomycete Sordaria macrospora. The P. confluens pro44 gene (PCON_06721) was used to complement the S. macrospora pro44 deletion mutant, showing functional conservation of this developmental regulator.
Traeger S, Altegoer F, Freitag M, Gabaldon T, Kempken F, Kumar A et al. The genome and development-dependent transcriptomes of Pyronema confluens: a window into fungal evolution. PLoS Genet. 2013;9(9):e1003820. DOI: 10.1371/journal.pgen.1003820
1553-7390
http://hdl.handle.net/10230/22480
http://dx.doi.org/10.1371/journal.pgen.1003820
The genome and development-dependent transcriptomes of Pyronema confluens: a window into fungal evolution
oai:repositori.upf.edu:10230/224812020-06-15T12:02:31Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Morales, Lucia
author
Noel, Benjamin
author
Porcel, Betina
author
Marcet Houben, Marina
author
Hullo, Marie-Françoise
author
Sacerdot, Christine
author
Tekaia, Fredj
author
Leh-Louis, Véronique
author
Despons, Laurence
author
Khanna, Varun
author
Aury, Jean-Marc
author
Barbe, Valérie
author
Coloux, Arnaud
author
Labadie, Karine
author
Pelletier, Eric
author
Souciet, Jean-Luc
author
Boekhout, Teun
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Wincker, Patrick
author
Dujon, Bernard
author
2013
The numerous yeast genome sequences presently available provide a rich source of information for functional as well as evolutionary genomics but unequally cover the large phylogenetic diversity of extant yeasts. We present here the complete sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata (CBS1993(T)), a nitrate-assimilating Saccharomycetales of uncertain taxonomy, isolated from tunnels of insect larvae underneath coniferous barks and characterized by its copious production of extracellular polysaccharides. The sequence is composed of seven scaffolds, one per chromosome, totaling 11.4 Mb and containing 6,029 protein-coding genes, 13.5% of which being interrupted by introns. This GC-rich yeast genome (45.7%) appears phylogenetically related with the few other nitrate-assimilating yeasts sequenced so far, Ogataea polymorpha, O. parapolymorpha, and Dekkera bruxellensis, with which it shares a very reduced number of tRNA genes, a novel tRNA sparing strategy, and a common nitrate assimilation cluster, three specific features to this group of yeasts. Centromeres were recognized in GC-poor troughs of each scaffold. The strain bears MAT alpha genes at a single MAT locus and presents a significant degree of conservation with Saccharomyces cerevisiae genes, suggesting that it can perform sexual cycles in nature, although genes involved in meiosis were not all recognized. The complete absence of conservation of synteny between K. capsulata and any other yeast genome described so far, including the three other nitrate-assimilating species, validates the interest of this species for long-range evolutionary genomic studies among Saccharomycotina yeasts.
Morales L, Noel B, Porcel B, Marcet-Houben M, Hullo MF, Sacerdot C et al. Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina). Genome Biol Evol. 2013;5(12):2524-39. DOI: 10.1093/gbe/evt201
1759-6653
http://hdl.handle.net/10230/22481
http://dx.doi.org/10.1093/gbe/evt201
Complete DNA sequence of Kuraishia capsulata illustrates novel genomic features among budding yeasts (Saccharomycotina)
oai:repositori.upf.edu:10230/224822020-06-15T11:56:08Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Jiménez Guri, Eva
author
Huerta Cepas, Jaime
author
Cozzuto, Luca
author
Wotton, Karl R.
author
Kang, Hui
author
Himmelbauer, Heinz
author
Roma, Guglielmo
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Jaeger, Johannes, 1973-
author
2013
BACKGROUND: Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). RESULTS: We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. CONCLUSIONS: We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies).
Jiménez-Guri E, Huerta-Cepas J, Cozzuto L, Wotton KR, Kang H, Himmelbauer H et al. Comparative transcriptomics of early dipteran development. BMC Genomics. 2013; 14:123. DOI: 10.1186/1471-2164-14-123
1471-2164
http://hdl.handle.net/10230/22482
http://dx.doi.org/10.1186/1471-2164-14-123
Comparative transcriptomics of early dipteran development
oai:repositori.upf.edu:10230/224832020-06-15T11:59:59Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Gabaldón Estevan, Juan Antonio, 1973-
author
Martin, Tiphaine
author
Marcet Houben, Marina
author
Durrens, Pascal
author
Bolotin Fukuhara, Monique
author
Lespinet, Olivier
author
Arnaise, Sylvie
author
Boisnard, Stéphanie
author
Aguileta, Gabriela
author
Atanasova, Ralitsa
author
Bouchier, Christiane
author
Couloux, Arnaud
author
Creno, Sophie
author
Almeida Cruz, José
author
Devillers, Hugo
author
Enache-Angoulvant, Aadela
author
Guitard, Juliette
author
Jaouen, Laure
author
Ma, Laurence
author
Marck, Christian
author
Neuvéglise, Cécile
author
Pelletier, Eric
author
Pinard, Amélie
author
Poulain, Julie
author
Recoquillay, Julien
author
Westhof, Eric
author
Wincker, Patrick
author
Dujon, Bernard
author
Hennequin, Christophe
author
Fairhead, Cécile
author
2013
BACKGROUND: Candida glabrata follows C. albicans as the second or third most prevalent cause of candidemia worldwide. These two pathogenic yeasts are distantly related, C. glabrata being part of the Nakaseomyces, a group more closely related to Saccharomyces cerevisiae. Although C. glabrata was thought to be the only pathogenic Nakaseomyces, two new pathogens have recently been described within this group: C. nivariensis and C. bracarensis. To gain insight into the genomic changes underlying the emergence of virulence, we sequenced the genomes of these two, and three other non-pathogenic Nakaseomyces, and compared them to other sequenced yeasts. RESULTS: Our results indicate that the two new pathogens are more closely related to the non-pathogenic N. delphensis than to C. glabrata. We uncover duplications and accelerated evolution that specifically affected genes in the lineage preceding the group containing N. delphensis and the three pathogens, which may provide clues to the higher propensity of this group to infect humans. Finally, the number of Epa-like adhesins is specifically enriched in the pathogens, particularly in C. glabrata. CONCLUSIONS: Remarkably, some features thought to be the result of adaptation of C. glabrata to a pathogenic lifestyle, are present throughout the Nakaseomyces, indicating these are rather ancient adaptations to other environments. Phylogeny suggests that human pathogenesis evolved several times, independently within the clade. The expansion of the EPA gene family in pathogens establishes an evolutionary link between adhesion and virulence phenotypes. Our analyses thus shed light onto the relationships between virulence and the recent genomic changes that occurred within the Nakaseomyces.
Gabaldón T, Martin T, Marcet-Houben M, Durrens P, Bolotin-Fukuhara M, Lespinet O et al. Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics. 2013;14:623. DOI: 10.1186/1471-2164-14-623
1471-2164
http://hdl.handle.net/10230/22483
http://dx.doi.org/10.1186/1471-2164-14-623
Comparative genomics of emerging pathogens in the Candida glabrata clade
oai:repositori.upf.edu:10230/224842020-06-16T07:13:46Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Pryszcz, Leszek Piotr, 1985-
author
Németh, Tibor
author
Gácser, Attila
author
Gabaldón Estevan, Juan Antonio, 1973-
author
2013
Invasive candidiasis is the most commonly reported invasive fungal infection worldwide. Although Candida albicans remains the main cause, the incidence of emerging Candida species, such as C. parapsilosis is increasing. It has been postulated that C. parapsilosis clinical isolates result from a recent global expansion of a virulent clone. However, the availability of a single genome for this species has so far prevented testing this hypothesis at genomic scales. We present here the sequence of three additional strains from clinical and environmental samples. Our analyses reveal unexpected patterns of genomic variation, shared among distant strains, that argue against the clonal expansion hypothesis. All strains carry independent expansions involving an arsenite transporter homolog, pointing to the existence of directional selection in the environment, and independent origins of the two clinical isolates. Furthermore, we report the first evidence for the existence of recombination in this species. Altogether, our results shed new light onto the dynamics of genome evolution in C. parapsilosis.
Pryszcz LP, Németh T, Gácser A, Gabaldón T. Unexpected genomic variability in clinical and environmental strains of the pathogenic yeast Candida parapsilosis. Genome Biol Evol. 2013;5(12):2382-92. DOI: 10.1093/gbe/evt185
1759-6653
http://hdl.handle.net/10230/22484
http://dx.doi.org/10.1093/gbe/evt185
Unexpected genomic variability in clinical and environmental strains of the pathogenic yeast Candida parapsilosis
oai:repositori.upf.edu:10230/224852020-06-16T07:16:24Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Huerta Cepas, Jaime
author
Capella Gutiérrez, Salvador Jesús, 1985-
author
Pryszcz, Leszek Piotr, 1985-
author
Marcet Houben, Marina
author
Gabaldón Estevan, Juan Antonio, 1973-
author
2014
Phylogenetic trees representing the evolutionary relationships of homologous genes are the entry point for many evolutionary analyses. For instance, the use of a phylogenetic tree can aid in the inference of orthology and paralogy relationships, and in the detection of relevant evolutionary events such as gene family expansions and contractions, horizontal gene transfer, recombination or incomplete lineage sorting. Similarly, given the plurality of evolutionary histories among genes encoded in a given genome, there is a need for the combined analysis of genome-wide collections of phylogenetic trees (phylomes). Here, we introduce a new release of PhylomeDB (http://phylomedb.org), a public repository of phylomes. Currently, PhylomeDB hosts 120 public phylomes, comprising >1.5 million maximum likelihood trees and multiple sequence alignments. In the current release, phylogenetic trees are annotated with taxonomic, protein-domain arrangement, functional and evolutionary information. PhylomeDB is also a major source for phylogeny-based predictions of orthology and paralogy, covering >10 million proteins across 1059 sequenced species. Here we describe newly implemented PhylomeDB features, and discuss a benchmark of the orthology predictions provided by the database, the impact of proteome updates and the use of the phylome approach in the analysis of newly sequenced genomes and transcriptomes.
Huerta-Cepas J, Capella-Gutiérrez S, Pryszcz LP, Marcet-Houben M, Gabaldón T. PhylomeDB v4: zooming into the plurality of evolutionary histories of a genome. Nucleic Acids Res. 2014;42(1):D897-D902. DOI 10.1093/nar/gkt1177
0305-1048
http://hdl.handle.net/10230/22485
http://dx.doi.org/10.1093/nar/gkt1177
PhylomeDB v4: zooming into the plurality of evolutionary histories of a genome
oai:repositori.upf.edu:10230/224862020-06-16T07:19:30Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Powell, Sean
author
Forslund, Kristoffer
author
Szklarczyk, Damian
author
Trachana, Kalliopi
author
Roth, Alexander
author
Huerta Cepas, Jaime
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Rattei, Thomas
author
Creevey, Chris
author
Kuhn, Michael
author
Jensen, Lars J.
author
Mering, Christian von
author
Bork, Peer
author
2014
With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.
Powell S, Forslund K, Szklarczyk D, Trachana K, Roth A, Huerta-Cepas J et al. eggNOG v4.0: nested orthology inference across 3686 organisms. Nucleic Acids Res. 2014;42(1):D231-D239. DOI: 10.1093/nar/gkt1253
0305-1048
http://hdl.handle.net/10230/22486
http://dx.doi.org/10.1093/nar/gkt1253
eggNOG v4.0: nested orthology inference across 3686 organisms
oai:repositori.upf.edu:10230/224932020-06-16T07:20:56Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Dohm, Juliane C.
author
Minoche, André E.
author
Holtgräwe, Daniela
author
Capella Gutiérrez, Salvador Jesús, 1985-
author
Zakrzewski, Falk
author
Tafer, Hakim
author
Rupp, Oliver
author
Sörensen, Thomas Rosleff
author
Stracke, Ralf
author
Reinhardt, Richard
author
Goesmann, Alexander
author
Kraft, Thomas
author
Schulz, Britta
author
Stadler, Peter F.
author
Schmidt, Thomas
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Lehrach, Hans
author
Weisshaar, Bernd
author
Himmelbauer, Heinz
author
2014
Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world's annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n = 18 chromosomes, has an estimated genome size of 714-758 megabases and shares an ancient genome triplication with other eudicot plants. Leafy beets have been cultivated since Roman times, but sugar beet is one of the most recently domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet. Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant's potential in energy biotechnology.
Dohm JC, Minoche AE, Holtgräwe D, Capella-Gutiérrez S, Zakrzewski F, Tafer H et al. The genome of the recently domesticated crop plant sugar beet (Beta vulgaris). Nature. 2014;505(7484):546-9. DOI: 10.1038/nature12817
0028-0836
http://hdl.handle.net/10230/22493
http://dx.doi.org/10.1038/nature12817
The genome of the recently domesticated crop plant sugar beet (Beta vulgaris)
oai:repositori.upf.edu:10230/225342020-06-25T09:27:48Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Morey Ramonell, Lluís
author
Aloia, Luigi
author
Cozzuto, Luca
author
Aznar Benitah, Salvador
author
Di Croce, Luciano
author
2013
The Polycomb repressive complex 1 (PRC1) is required for decisions of stem cell fate. In mouse embryonic stem cells (ESCs), two major variations of PRC1 complex, defined by the mutually exclusive presence of Cbx7 or RYBP, have been identified. Here, we show that although the genomic localization of the Cbx7- and RYBP-containing PRC1 complexes overlaps in certain genes, it can also be mutually exclusive. At the molecular level, Cbx7 is necessary for recruitment of Ring1B to chromatin, whereas RYBP enhances the PRC1 enzymatic activity. Genes occupied by RYBP show lower levels of Ring1B and H2AK119ub and are consequently more highly transcribed than those bound by Cbx7. At the functional level, we show that genes occupied by RYBP are primarily involved in the regulation of metabolism and cell-cycle progression, whereas those bound by Cbx7 predominantly control early-lineage commitment of ESCs. Altogether, our results indicate that different PRC1 subtypes establish a complex pattern of gene regulation that regulates common and nonoverlapping aspects of ESC pluripotency and differentiation.
Morey L, Aloia L, Cozzuto L, Benitah SA, Di Croce L. RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells. Cell Rep. 2013;3(1):60-9. DOI: 10.1016/j.celrep.2012.11.026
2211-1247
http://hdl.handle.net/10230/22534
http://dx.doi.org/10.1016/j.celrep.2012.11.026
RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells
oai:repositori.upf.edu:10230/225532021-06-08T08:06:28Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Agostini, Federico, 1985-
author
Cirillo, Davide
author
Bolognesi, Benedetta
author
Tartaglia, Gian Gaetano
author
2013
The transcriptional silencing of one of the female X-chromosomes is a finely regulated process that requires accumulation in cis of the long non-coding RNA X-inactive-specific transcript (Xist) followed by a series of epigenetic modifications. Little is known about the molecular machinery regulating initiation and maintenance of chromosomal silencing. Here, we introduce a new version of our algorithm catRAPID to investigate Xist associations with a number of proteins involved in epigenetic regulation, nuclear scaffolding, transcription and splicing processes. Our method correctly identifies binding regions and affinities of protein interactions, providing a powerful theoretical framework for the study of X-chromosome inactivation and other events mediated by ribonucleoprotein associations.
Agostini F, Cirillo D, Bolognesi B, Tartaglia GG. X-inactivation: quantitative predictions of protein interactions in the Xist network. Nucleic Acids Res. 2013; 41(1): e31. DOI: 10.1093/nar/gks968
0305-1048
http://hdl.handle.net/10230/22553
http://dx.doi.org/10.1093/nar/gks968
X-inactivation: quantitative predictions of protein interactions in the Xist network
oai:repositori.upf.edu:10230/225542020-06-16T07:31:03Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Agostini, Federico, 1985-
author
Zanzoni, Andreas
author
Klus, Petr, 1985-
author
Marchese, Domenica, 1986-
author
Cirillo, Davide
author
Tartaglia, Gian Gaetano
author
2013
SUMMARY: Here we introduce catRAPID omics, a server for large-scale calculations of protein-RNA interactions. Our web server allows (i) predictions at proteomic and transcriptomic level; (ii) use of protein and RNA sequences without size restriction; (iii) analysis of nucleic acid binding regions in proteins; and (iv) detection of RNA motifs involved in protein recognition. RESULTS: We developed a web server to allow fast calculation of ribonucleoprotein associations in Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae and Xenopus tropicalis (custom libraries can be also generated). The catRAPID omics was benchmarked on the recently published RNA interactomes of Serine/arginine-rich splicing factor 1 (SRSF1), Histone-lysine N-methyltransferase EZH2 (EZH2), TAR DNA-binding protein 43 (TDP43) and RNA-binding protein FUS (FUS) as well as on the protein interactomes of U1/U2 small nucleolar RNAs, X inactive specific transcript (Xist) repeat A region (RepA) and Crumbs homolog 3 (CRB3) 3'-untranslated region RNAs. Our predictions are highly significant (P < 0.05) and will help the experimentalist to identify candidates for further validation./nAVAILABILITY: catRAPID omics can be freely accessed on the Web at http://s.tartaglialab.com/catrapid/omics. Documentation, tutorial and FAQs are available at http://s.tartaglialab.com/page/catrapid_group.
Agostini F, Zanzoni A, Klus P, Marchese D, Cirillo D, Tartaglia GG. catRAPID omics: a web server for large-scale prediction of protein-RNA interactions. Bioinformatics. 2013;29(22):2928-30. DOI: 10.1093/bioinformatics/btt495
1367-4803
http://hdl.handle.net/10230/22554
http://dx.doi.org/10.1093/bioinformatics/btt495
catRAPID omics: a web server for large-scale prediction of protein-RNA interactions
oai:repositori.upf.edu:10230/225552020-06-16T07:32:59Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Zanzoni, Andreas
author
Marchese, Domenica, 1986-
author
Agostini, Federico, 1985-
author
Bolognesi, Benedetta
author
Cirillo, Davide
author
Botta-Orfila, Maria
author
Livi, Carmen Maria
author
Rodriguez-Mulero, Silvia
author
Tartaglia, Gian Gaetano
author
2013
Previous evidence indicates that a number of proteins are able to interact with cognate mRNAs. These autogenous associations represent important regulatory mechanisms that control gene expression at the translational level. Using the catRAPID approach to predict the propensity of proteins to bind to RNA, we investigated the occurrence of autogenous associations in the human proteome. Our algorithm correctly identified binding sites in well-known cases such as thymidylate synthase, tumor suppressor P53, synaptotagmin-1, serine/ariginine-rich splicing factor 2, heat shock 70 kDa, ribonucleic particle-specific U1A and ribosomal protein S13. In addition, we found that several other proteins are able to bind to their own mRNAs. A large-scale analysis of biological pathways revealed that aggregation-prone and structurally disordered proteins have the highest propensity to interact with cognate RNAs. These findings are substantiated by experimental evidence on amyloidogenic proteins such as TAR DNA-binding protein 43 and fragile X mental retardation protein. Among the amyloidogenic proteins, we predicted that Parkinson's disease-related α-synuclein is highly prone to interact with cognate transcripts, which suggests the existence of RNA-dependent factors in its function and dysfunction. Indeed, as aggregation is intrinsically concentration dependent, it is possible that autogenous interactions play a crucial role in controlling protein homeostasis.
Zanzoni A, Marchese D, Agostini F, Bolognesi B, Cirillo D, Botta-Orfila M et al. Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein. Nucleic Acids Res. 2013;41(22):9987-98. DOI: 10.1093/nar/gkt794
0305-1048
http://hdl.handle.net/10230/22555
http://dx.doi.org/10.1093/nar/gkt794
Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein
oai:repositori.upf.edu:10230/225562021-06-08T08:18:57Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Ciryam, Prajwal
author
Tartaglia, Gian Gaetano
author
Morimoto, Richard I.
author
Dobson, Christopher M.
author
Vendruscolo, Michele
author
2013
The maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or aging. A crucial question in this context is why only certain proteins appear to aggregate readily in vivo, whereas others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. We find that these supersaturated proteins represent a metastable subproteome involved in pathological aggregation during stress and aging and are overrepresented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging.
Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M. Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep. 2013; 5(3):781-790. DOI: 10.1016/j.celrep.2013.09.043
2211-1247
http://hdl.handle.net/10230/22556
http://dx.doi.org/10.1016/j.celrep.2013.09.043
Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins
oai:repositori.upf.edu:10230/225582020-06-16T07:36:34Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Acosta, Juan Carlos
author
Banito, Ana
author
Wuestefeld, Torsten
author
Georgilis, Athena
author
Janich, Peggy, 1981-
author
Morton, Jennifer P.
author
Athineos, Dimitris
author
Kang, Tae-Won
author
Lasitschka, Felix
author
Andrulis, Mindaugas
author
Pascual, Gloria
author
Morris, Kelly J.
author
Khan, Sadaf
author
Jin, Hong
author
Dharmalingam, Gopuraja
author
Snijders, Ambrosius P.
author
Carroll, Thomas
author
Capper, David
author
Pritchard, Catrin
author
Inman, Gareth J.
author
Longerich, Thomas
author
Sansom, Owen J.
author
Aznar Benitah, Salvador
author
Zender, Lars
author
Gil, Jesús
author
2013
Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15(INK4b) and p21(CIP1). Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo.
Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15(8):978-90. DOI: 10.1038/ncb2784
1465-7392
http://hdl.handle.net/10230/22558
http://dx.doi.org/10.1038/ncb2784
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
oai:repositori.upf.edu:10230/225592020-06-16T07:43:43Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Cirillo, Davide
author
Agostini, Federico, 1985-
author
Klus, Petr, 1985-
author
Marchese, Domenica, 1986-
author
Rodríguez, Silvia
author
Bolognesi, Benedetta
author
Tartaglia, Gian Gaetano
author
2013
Increasing evidence indicates that RNA plays an active role in a number of neurodegenerative diseases. We recently introduced a theoretical framework, catRAPID, to predict the binding ability of protein and RNA molecules. Here, we use catRAPID to investigate ribonucleoprotein interactions linked to inherited intellectual disability, amyotrophic lateral sclerosis, Creutzfeuld-Jakob, Alzheimer's, and Parkinson's diseases. We specifically focus on (1) RNA interactions with fragile X mental retardation protein FMRP; (2) protein sequestration caused by CGG repeats; (3) noncoding transcripts regulated by TAR DNA-binding protein 43 TDP-43; (4) autogenous regulation of TDP-43 and FMRP; (5) iron-mediated expression of amyloid precursor protein APP and α-synuclein; (6) interactions between prions and RNA aptamers. Our results are in striking agreement with experimental evidence and provide new insights in processes associated with neuronal function and misfunction.
Cirillo D, Agostini F, Klus P, Marchese D, Rodriguez S, Bolognesi B et al. Neurodegenerative diseases: quantitative predictions of protein-RNA interactions. RNA. 2013;19(2):129-40. DOI: 10.1261/rna.034777.112
1355-8382
http://hdl.handle.net/10230/22559
http://dx.doi.org/10.1261/rna.034777.112
Neurodegenerative diseases: quantitative predictions of protein-RNA interactions
oai:repositori.upf.edu:10230/225692020-06-16T07:48:33Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Foresti, Ombretta
author
Ruggiano, Annamaria, 1985-
author
Hannibal-Bach, Hans K.
author
Ejsing, Christer S.
author
Carvalho, Pedro C.
author
2013
Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway.
Foresti O, Ruggiano A, Hannibal-Bach HK, Ejsing CS, Carvalho P. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. eLife. 2013;2:e00953. DOI: 10.7554/eLife.00953
2050-084X
http://hdl.handle.net/10230/22569
http://dx.doi.org/10.7554/eLife.00953
Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4
oai:repositori.upf.edu:10230/225872020-06-16T08:10:06Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Alioto, Tyler
author
Picardi, Ernesto
author
Guigó Serra, Roderic
author
Pesole, Graziano
author
2013
New genomes are being sequenced at an increasingly rapid rate, far outpacing the rate at which manual gene annotation can be performed. Automated genome annotation is thus necessitated by this growth in genome projects; however, full-fledged annotation systems are usually home-grown and customized to a particular genome. There is thus a renewed need for accurate ab initio gene prediction methods. However, it is apparent that fully ab initio methods fall short of the required level of sensitivity and specificity for a quality annotation. Evidence in the form of expressed sequences gives the single biggest improvement in accuracy when used to inform gene predictions. Here, we present a lightweight pipeline for first-pass gene prediction on newly sequenced genomes. The two main components are ASPic, a program that derives highly accurate, albeit not necessarily complete, EST-based transcript annotations from EST alignments, and GeneID, a standard gene prediction program, which we have modified to take as evidence intron annotations. The introns output by ASPic CDS predictions is given to GeneID to constrain the exon-chaining process and produce predictions consistent with the underlying EST alignments. The pipeline was successfully tested on the entire C. elegans genome and the 44 ENCODE human pilot regions.
Alioto T, Picardi E, Guigó R, Pesole G. ASPic-GeneID: a lightweight pipeline for gene prediction and alternative isoforms detection. Biomed Res Int. 2013;2013:502827. DOI: 10.1155/2013/502827
2314-6133
http://hdl.handle.net/10230/22587
http://dx.doi.org/10.1155/2013/502827
ASPic-GeneID: a lightweight pipeline for gene prediction and alternative isoforms detection
oai:repositori.upf.edu:10230/225882020-06-16T08:14:28Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Stamatoyannopoulos, John A.
author
Guigó Serra, Roderic
author
Djebali, Sarah
author
Lagarde, Julien
author
Adams, Leslie B.
author
2012
To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.
Stamatoyannopoulos JA, Snyder M, Hardison R, Ren B, Gingeras T, Gilbert DM et al. An encyclopedia of mouse DNA elements (Mouse ENCODE). Genome Biol. 2012;13(8):418. DOI: 10.1186/gb-2012-13-8-418
1465-6906
http://hdl.handle.net/10230/22588
http://dx.doi.org/10.1186/gb-2012-13-8-418
An encyclopedia of mouse DNA elements (Mouse ENCODE)
oai:repositori.upf.edu:10230/225892020-06-16T08:18:30Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Dong, Xianjun
author
Greven, Melissa C.
author
Kundaje, Anshul
author
Djebali, Sarah
author
Brown, James B.
author
Cheng, Chao
author
Gingeras, Thomas R.
author
Gerstein, Mark B.
author
Guigó Serra, Roderic
author
Birney, Ewan
author
Weng, Zhiping
author
2012
BACKGROUND: Previous work has demonstrated that chromatin feature levels correlate with gene expression. The ENCODE project enables us to further explore this relationship using an unprecedented volume of data. Expression levels from more than 100,000 promoters were measured using a variety of high-throughput techniques applied to RNA extracted by different protocols from different cellular compartments of several human cell lines. ENCODE also generated the genome-wide mapping of eleven histone marks, one histone variant, and DNase I hypersensitivity sites in seven cell lines. RESULTS: We built a novel quantitative model to study the relationship between chromatin features and expression levels. Our study not only confirms that the general relationships found in previous studies hold across various cell lines, but also makes new suggestions about the relationship between chromatin features and gene expression levels. We found that expression status and expression levels can be predicted by different groups of chromatin features, both with high accuracy. We also found that expression levels measured by CAGE are better predicted than by RNA-PET or RNA-Seq, and different categories of chromatin features are the most predictive of expression for different RNA measurement methods. Additionally, PolyA+ RNA is overall more predictable than PolyA- RNA among different cell compartments, and PolyA+ cytosolic RNA measured with RNA-Seq is more predictable than PolyA+ nuclear RNA, while the opposite is true for PolyA- RNA. CONCLUSIONS: Our study provides new insights into transcriptional regulation by analyzing chromatin features in different cellular contexts.
Dong X, Greven MC, Kundaje A, Djebali S, Brown JB, Cheng C et al. Modeling gene expression using chromatin features in various cellular contexts. Genome Biol. 2012;13(9):R53. DOI: 10.1186/gb-2012-13-9-r53
1465-6906
http://hdl.handle.net/10230/22589
http://dx.doi.org/10.1186/gb-2012-13-9-r53
Modeling gene expression using chromatin features in various cellular contexts
oai:repositori.upf.edu:10230/225902020-06-16T08:21:02Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Mariotti, Marco, 1984-
author
Ridge, Perry G.
author
Zhang, Yan
author
Lobanov, Alexei V.
author
Pringle, Thomas H.
author
Guigó Serra, Roderic
author
Hatfield, Dolph L.
author
Gladyshev, Vadim N.
author
2012
BACKGROUND: Selenium is an essential trace element in mammals due to its presence in proteins in the form of selenocysteine (Sec). Human genome codes for 25 Sec-containing protein genes, and mouse and rat genomes for 24. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the selenoproteomes of 44 sequenced vertebrates by applying gene prediction and phylogenetic reconstruction methods, supplemented with the analyses of gene structures, alternative splicing isoforms, untranslated regions, SECIS elements, and pseudogenes. In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes. We define the ancestral vertebrate (28 proteins) and mammalian (25 proteins) selenoproteomes, and describe how they evolved along lineages through gene duplication (20 events), gene loss (10 events) and replacement of Sec with cysteine (12 events). We show that an intronless selenophosphate synthetase 2 gene evolved in early mammals and replaced functionally the original multiexon gene in placental mammals, whereas both genes remain in marsupials. Mammalian thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an ancestral glutaredoxin-domain containing enzyme, still present in fish. Selenoprotein V and GPx6 evolved specifically in placental mammals from duplications of SelW and GPx3, respectively, and GPx6 lost Sec several times independently. Bony fishes were characterized by duplications of several selenoprotein families (GPx1, GPx3, GPx4, Dio3, MsrB1, SelJ, SelO, SelT, SelU1, and SelW2). Finally, we report identification of new isoforms for several selenoproteins and describe unusually conserved selenoprotein pseudogenes. CONCLUSIONS/SIGNIFICANCE: This analysis represents the first comprehensive survey of the vertebrate and mammal selenoproteomes, and depicts their evolution along lineages. It also provides a wealth of information on these selenoproteins and their forms.
Mariotti M, Ridge PG, Zhang Y, Lobanov AV, Pringle TH, Guigo R et al. Composition and evolution of the vertebrate and mammalian selenoproteomes. PLoS One. 2012;7(3):e33066. DOI: 10.1371/journal.pone.0033066
1932-6203
http://hdl.handle.net/10230/22590
http://dx.doi.org/10.1371/journal.pone.0033066
Composition and evolution of the vertebrate and mammalian selenoproteomes
oai:repositori.upf.edu:10230/225912020-06-16T08:23:11Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Djebali, Sarah
author
Lagarde, Julien
author
Lacroix, Vincent
author
Foissac, Sylvain
author
Ribeca, Paolo
author
Martin, David
author
Guigó Serra, Roderic
author
Gingeras, Thomas R.
author
2012
The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network.
Djebali S, Lagarde J, Kapranov P, Lacroix V, Borel C, Mudge JM et al. Evidence for transcript networks composed of chimeric RNAs in human cells. PLoS One. 2012;7(1):e28213. DOI: 10.1371/journal.pone.0028213
1932-6203
http://hdl.handle.net/10230/22591
http://dx.doi.org/10.1371/journal.pone.0028213
Evidence for transcript networks composed of chimeric RNAs in human cells
oai:repositori.upf.edu:10230/225922020-06-16T08:25:31Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Derrien, Thomas
author
Estellé, Jordi
author
Marco Sola, Santiago
author
Knowles, David G.
author
Raineri, Emanuele
author
Guigó Serra, Roderic
author
Ribeca, Paolo
author
2012
We present a fast mapping-based algorithm to compute the mappability of each region of a reference genome up to a specified number of mismatches. Knowing the mappability of a genome is crucial for the interpretation of massively parallel sequencing experiments. We investigate the properties of the mappability of eukaryotic DNA/RNA both as a whole and at the level of the gene family, providing for various organisms tracks which allow the mappability information to be visually explored. In addition, we show that mappability varies greatly between species and gene classes. Finally, we suggest several practical applications where mappability can be used to refine the analysis of high-throughput sequencing data (SNP calling, gene expression quantification and paired-end experiments). This work highlights mappability as an important concept which deserves to be taken into full account, in particular when massively parallel sequencing technologies are employed. The GEM mappability program belongs to the GEM (GEnome Multitool) suite of programs, which can be freely downloaded for any use from its website (http://gemlibrary.sourceforge.net).
Derrien T, Estellé J, Marco Sola S, Knowles DG, Raineri E, Guigó R et al./nFast computation and applications of genome mappability. PLoS One. 2012;7(1):e30377. DOI: 10.1371/journal.pone.0030377
1932-6203
http://hdl.handle.net/10230/22592
http://dx.doi.org/10.1371/journal.pone.0030377
Fast computation and applications of genome mappability
oai:repositori.upf.edu:10230/226312020-06-16T09:16:01Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Pervouchine, Dmitri D.
author
Knowles, David G.
author
Guigó Serra, Roderic
author
2013
MOTIVATION: Novel technologies brought in unprecedented amounts of high-throughput sequencing data along with great challenges in their analysis and interpretation. The percent-spliced-in (PSI, ) metric estimates the incidence of single-exon-skipping events and can be computed directly by counting reads that align to known or predicted splice junctions. However, the majority of human splicing events are more complex than single-exon skipping. RESULTS: In this short report, we present a framework that generalizes the metric to arbitrary classes of splicing events. We change the view from exon centric to intron centric and split the value of into two indices, and , measuring the rate of splicing at the 5' and 3' end of the intron, respectively. The advantage of having two separate indices is that they deconvolute two distinct elementary acts of the splicing reaction. The completeness of splicing index is decomposed in a similar way. This framework is implemented as bam2ssj, a BAM-file-processing pipeline for strand-specific counting of reads that align to splice junctions or overlap with splice sites. It can be used as a consistent protocol for quantifying splice junctions from RNA-seq data because no such standard procedure currently exists. AVAILABILITY: The C code of bam2ssj is open source and is available at https://github.com/pervouchine/bam2ssj. CONTACT: dp@crg.eu.
Pervouchine DD, Knowles DG, Guigó R. Intron-centric estimation of alternative splicing from RNA-seq data. Bioinformatics. 2013;29(2):273-4. DOI: 10.1093/bioinformatics/bts678
1367-4803
http://hdl.handle.net/10230/22631
http://dx.doi.org/10.1093/bioinformatics/bts678
Intron-centric estimation of alternative splicing from RNA-seq data
oai:repositori.upf.edu:10230/226322020-06-16T09:21:03Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Derrien, Thomas
author
Guigó Serra, Roderic
author
Johnson, Rory
author
2012
The transcriptome of a cell is represented by a myriad of different RNA molecules with and without protein-coding capacities. In recent years, advances in sequencing technologies have allowed researchers to more fully appreciate the complexity of whole transcriptomes, showing that the vast majority of the genome is transcribed, producing a diverse population of non-protein coding RNAs (ncRNAs). Thus, the biological significance of non-coding RNAs (ncRNAs) have been largely underestimated. Amongst these multiple classes of ncRNAs, the long non-coding RNAs (lncRNAs) are apparently the most numerous and functionally diverse. A small but growing number of lncRNAs have been experimentally studied, and a view is emerging that these are key regulators of epigenetic gene regulation in mammalian cells. LncRNAs have already been implicated in human diseases such as cancer and neurodegeneration, highlighting the importance of this emergent field. In this article, we review the catalogs of annotated lncRNAs and the latest advances in our understanding of lncRNAs.
Derrien T, Guigó R, Johnson R. The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter". Front Genet. 2012;2:107. DOI: 10.3389/fgene.2011.00107
1664-8021
http://hdl.handle.net/10230/22632
http://dx.doi.org/10.3389/fgene.2011.00107
The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter"
oai:repositori.upf.edu:10230/226332020-06-16T09:22:32Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Frenkel-Morgenstern, Milana
author
Lacroix, Vincent
author
Ezkurdia, Iakes
author
Levin, Yishai
author
Gabashvili, Alexandra
author
Prilusky, Jaime
author
Pozo, Angela del
author
Tress, Michael
author
Johnson, Rory
author
Guigó Serra, Roderic
author
Valencia, Alfonso
author
2012
Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per Kilobase per Million mapped reads). We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans.
Frenkel-Morgenstern M, Lacroix V, Ezkurdia I, Levin Y, Gabashvili A, Prilusky J et al. Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts. Genome Res. 2012;22(7):1231-42. DOI: 10.1101/gr.130062.111
1088-9051
http://hdl.handle.net/10230/22633
http://dx.doi.org/10.1101/gr.130062.111
Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts
oai:repositori.upf.edu:10230/226342020-06-16T09:30:02Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Howald, Cédric
author
Tanzer, Andrea
author
Chrast, Jacqueline
author
Kokocinski, Felix
author
Derrien, Thomas
author
Walters, Nathalie
author
González, José M.
author
Frankish, Adam
author
Aken, Bronwen
author
Hourlier, Thibaut
author
Vogel, Jan-Hinnerk
author
White, Simon
author
Searle, Stephen
author
Harrow, Jennifer
author
Hubbard, Tim J.
author
Guigó Serra, Roderic
author
Reymond, Alexandre
author
2012
Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon-exon junctions were evaluated by RT-PCR amplification followed by highly multiplexed sequencing readout, a method we called RT-PCR-seq. Seventy-nine percent of all assessed junctions are confirmed by this evaluation procedure, demonstrating the high quality of the GENCODE gene set. RT-PCR-seq was also efficient to screen gene models predicted using the Human Body Map (HBM) RNA-seq data. We validated 73% of these predictions, thus confirming 1168 novel genes, mostly noncoding, which will further complement the GENCODE annotation. Our novel experimental validation pipeline is extremely sensitive, far more than unbiased transcriptome profiling through RNA sequencing, which is becoming the norm. For example, exon-exon junctions unique to GENCODE annotated transcripts are five times more likely to be corroborated with our targeted approach than with extensive large human transcriptome profiling. Data sets such as the HBM and ENCODE RNA-seq data fail sampling of low-expressed transcripts. Our RT-PCR-seq targeted approach also has the advantage of identifying novel exons of known genes, as we discovered unannotated exons in 11% of assessed introns. We thus estimate that at least 18% of known loci have yet-unannotated exons. Our work demonstrates that the cataloging of all of the genic elements encoded in the human genome will necessitate a coordinated effort between unbiased and targeted approaches, like RNA-seq and RT-PCR-seq.
Howald C, Tanzer A, Chrast J, Kokocinski F, Derrien T, Walters N et al. Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome. Genome Res. 2012;22(9):1698-710. DOI: 10.1101/gr.134478.111
1088-9051
http://hdl.handle.net/10230/22634
http://dx.doi.org/10.1101/gr.134478.111
Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome
oai:repositori.upf.edu:10230/226352020-06-16T09:31:00Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Tilgner, Hagen, 1980-
author
Knowles, David G.
author
Johnson, Rory
author
Davis, Carrie A.
author
Chakrabortty, Sudipto
author
Djebali, Sarah
author
Curado, Joao
author
Snyder, Michael
author
Gingeras, Thomas R.
author
Guigó Serra, Roderic
author
2012
Splicing remains an incompletely understood process. Recent findings suggest that chromatin structure participates in its regulation. Here, we analyze the RNA from subcellular fractions obtained through RNA-seq in the cell line K562. We show that in the human genome, splicing occurs predominantly during transcription. We introduce the coSI measure, based on RNA-seq reads mapping to exon junctions and borders, to assess the degree of splicing completion around internal exons. We show that, as expected, splicing is almost fully completed in cytosolic polyA+ RNA. In chromatin-associated RNA (which includes the RNA that is being transcribed), for 5.6% of exons, the removal of the surrounding introns is fully completed, compared with 0.3% of exons for which no intron-removal has occurred. The remaining exons exist as a mixture of spliced and fewer unspliced molecules, with a median coSI of 0.75. Thus, most RNAs undergo splicing while being transcribed: "co-transcriptional splicing." Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA fractions and other nonspliceosomal snRNAs. CoSI scores decrease along the gene, pointing to a "first transcribed, first spliced" rule, yet more downstream exons carry other characteristics, favoring rapid, co-transcriptional intron removal. Exons with low coSI values, that is, in the process of being spliced, are enriched with chromatin marks, consistent with a role for chromatin in splicing during transcription. For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases.
Tilgner H, Knowles DG, Johnson R, Davis CA, Chakrabortty S, Djebali S et al. Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs. Genome Res. 2012;22(9):1616-25. DOI: 10.1101/gr.134445.111
1088-9051
http://hdl.handle.net/10230/22635
http://dx.doi.org/10.1101/gr.134445.111
Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs
oai:repositori.upf.edu:10230/226362020-06-16T09:32:00Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Harrow, Jennifer
author
Tanzer, Andrea
author
Guigó Serra, Roderic
author
Hubbard, Tim J.
author
2012
The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.
Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22(9):1760-74. DOI: 10.1101/gr.135350.111
1088-9051
http://hdl.handle.net/10230/22636
http://dx.doi.org/10.1101/gr.135350.111
GENCODE: the reference human genome annotation for The ENCODE Project
oai:repositori.upf.edu:10230/226372020-06-16T09:32:58Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Derrien, Thomas
author
Johnson, Rory
author
Bussotti, Giovanni, 1983-
author
Tanzer, Andrea
author
Djebali, Sarah
author
Tilgner, Hagen, 1980-
author
Guernec, Gregory
author
Martin, David
author
Merkel, Angelika
author
Knowles, David G.
author
Lagarde, Julien
author
Veeravalli, Lavanya
author
Ruan, Xiaoan
author
Ruan, Yijun
author
Lassmann, Timo
author
Carninci, Piero
author
Brown, James B.
author
Lipovich, Leonard
author
González, José M.
author
Thomas, Mark
author
Davis, Carrie A.
author
Shiekhattar, Ramin
author
Gingeras, Thomas R.
author
Hubbard, Tim J.
author
Notredame, Cedric
author
Harrow, Jennifer
author
Guigó Serra, Roderic
author
2012
The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775-89. DOI: 10.1101/gr.132159.111
1088-9051
http://hdl.handle.net/10230/22637
http://dx.doi.org/10.1101/gr.132159.111
The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression
oai:repositori.upf.edu:10230/226382020-06-16T09:37:53Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Cheng, Chao
author
Alexander, Roger
author
Min, Renqiang
author
Leng, Jing
author
Yip, Kevin Y.
author
Rozowsky, Joel S.
author
Yan, Koon-Kiu
author
Dong, Xianjun
author
Djebali, Sarah
author
Ruan, Yijun
author
Davis, Carrie A.
author
Carninci, Piero
author
Lassmann, Timo
author
Gingeras, Thomas R.
author
Guigó Serra, Roderic
author
Birney, Ewan
author
Weng, Zhiping
author
Snyder, Michael
author
Gerstein, Mark B.
author
2012
Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.
Cheng C, Alexander R, Min R, Leng J, Yip KY, Rozowsky J et al. Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res. 2012;22(9):1658-67. DOI: 10.1101/gr.136838.111
1088-9051
http://hdl.handle.net/10230/22638
http://dx.doi.org/10.1101/gr.136838.111
Understanding transcriptional regulation by integrative analysis of transcription factor binding data
oai:repositori.upf.edu:10230/226392020-06-16T09:38:41Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Knowles, David G.
author
Röder, Maik
author
Merkel, Angelika
author
Guigó Serra, Roderic
author
2013
MOTIVATION: The avalanche of data arriving since the development of NGS technologies have prompted the need for developing fast, accurate and easily automated bioinformatic tools capable of dealing with massive datasets. Among the most productive applications of NGS technologies is the sequencing of cellular RNA, known as RNA-Seq. Although RNA-Seq provides similar or superior dynamic range than microarrays at similar or lower cost, the lack of standard and user-friendly pipelines is a bottleneck preventing RNA-Seq from becoming the standard for transcriptome analysis. RESULTS: In this work we present a pipeline for processing and analyzing RNA-Seq data, that we have named Grape (Grape RNA-Seq Analysis Pipeline Environment). Grape supports raw sequencing reads produced by a variety of technologies, either in FASTA or FASTQ format, or as prealigned reads in SAM/BAM format. A minimal Grape configuration consists of the file location of the raw sequencing reads, the genome of the species and the corresponding gene and transcript annotation. Grape first runs a set of quality control steps, and then aligns the reads to the genome, a step that is omitted for prealigned read formats. Grape next estimates gene and transcript expression levels, calculates exon inclusion levels and identifies novel transcripts. Grape can be run on a single computer or in parallel on a computer cluster. It is distributed with specific mapping and quantification tools, but given its modular design, any tool supporting popular data interchange formats can be integrated. AVAILABILITY: Grape can be obtained from the Bioinformatics and Genomics website at: http://big.crg.cat/services/grape.
Knowles DG, Röder M, Merkel A, Guigó R. Grape RNA-Seq analysis pipeline environment. Bioinformatics. 2013;29(5):614-21. DOI: 10.1093/bioinformatics/btt016
1367-4803
http://hdl.handle.net/10230/22639
http://dx.doi.org/10.1093/bioinformatics/btt016
Grape RNA-Seq analysis pipeline environment
oai:repositori.upf.edu:10230/230722023-11-10T14:08:10Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
ENCODE Project Consortium
author
Dunham, Ian
author
Guigó Serra, Roderic
author
Birney, Ewan
author
2012
The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
ENCODE Project Consortium, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57-74. DOI: 10.1038/nature11247
0028-0836
http://hdl.handle.net/10230/23072
http://dx.doi.org/10.1038/nature11247
An integrated encyclopedia of DNA elements in the human genome
oai:repositori.upf.edu:10230/230732020-06-17T07:27:10Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Djebali, Sarah
author
Merkel, Angelika
author
Tanzer, Andrea
author
Lagarde, Julien
author
Röder, Maik
author
Curado, Joao
author
Derrien, Thomas
author
Ferreira, Pedro G.
author
González, David
author
Johnson, Rory
author
Kingswood, Colin
author
Ribeca, Paolo
author
Sammeth, Michael
author
Skancke, Jorgen
author
Tilgner, Hagen, 1980-
author
Guigó Serra, Roderic
author
Gingeras, Thomas R.
author
2012
Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101-8. DOI: 10.1038/nature11233
0028-0836
http://hdl.handle.net/10230/23073
http://dx.doi.org/10.1038/nature11233
Landscape of transcription in human cells
oai:repositori.upf.edu:10230/230742020-06-17T07:19:36Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Tomato Genome Consortium
author
Sato, S.
author
Guigó Serra, Roderic
author
Cámara, Francisco
author
Gianese, S.
author
2012
Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium, and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.
The Tomato Genome Consortium, Sato S, Tabata S, Hirakawa H, Asamizu E, Shirasawa K et al. The tomato genome sequence provides insights into fleshy fruit evolution. Nature. 2012; 485(7400): 635-41. DOI: 10.1038/nature11119
0028-0836
http://hdl.handle.net/10230/23074
http://dx.doi.org/10.1038/nature11119
The tomato genome sequence provides insights into fleshy fruit evolution
oai:repositori.upf.edu:10230/230952020-06-17T07:36:08Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
GTEx Consortium
author
Lonsdale, John
author
Guigó Serra, Roderic
author
Monlong, Jean
author
Sammeth, Michael
author
Moore, Helen F.
author
2013
Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6):580-5. DOI: 10.1038/ng.2653
1061-4036
http://hdl.handle.net/10230/23095
http://dx.doi.org/10.1038/ng.2653
The Genotype-Tissue Expression (GTEx) project
oai:repositori.upf.edu:10230/230962020-06-17T07:38:38Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Steijger, Tamara
author
Guigó Serra, Roderic
author
RGASP Consortium
author
2013
We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete transcript components with high success rates but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression-level estimates also varied widely across methods, even when based on similar transcript models. Consequently, the complexity of higher eukaryotic genomes imposes severe limitations on transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation RNA-seq data.
Steijger T, Abril JF, Engström PG, Kokocinski F, Hubbard TJ, Guigó R et al. Assessment of transcript reconstruction methods for RNA-seq. Nat Methods. 2013;10(12):1177-84. DOI: 10.1038/nmeth.2714
1548-7091
http://hdl.handle.net/10230/23096
http://dx.doi.org/10.1038/nmeth.2714
Assessment of transcript reconstruction methods for RNA-seq
oai:repositori.upf.edu:10230/230992015-12-02T17:58:01Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238oai:repositori.upf.edu:10230/231002021-06-08T08:03:00Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Griebel, Thasso
author
Zacher, Benedikt
author
Ribeca, Paolo
author
Raineri, Emanuele
author
Lacroix, Vincent
author
Guigó Serra, Roderic
author
Sammeth, Michael
author
2012
High-throughput sequencing of cDNA libraries constructed from cellular RNA complements (RNA-Seq) naturally provides a digital quantitative measurement for every expressed RNA molecule. Nature, impact and mutual interference of biases in different experimental setups are, however, still poorly understood-mostly due to the lack of data from intermediate protocol steps. We analysed multiple RNA-Seq experiments, involving different sample preparation protocols and sequencing platforms: we broke them down into their common--and currently indispensable--technical components (reverse transcription, fragmentation, adapter ligation, PCR amplification, gel segregation and sequencing), investigating how such different steps influence abundance and distribution of the sequenced reads. For each of those steps, we developed universally applicable models, which can be parameterised by empirical attributes of any experimental protocol. Our models are implemented in a computer simulation pipeline called the Flux Simulator, and we show that read distributions generated by different combinations of these models reproduce well corresponding evidence obtained from the corresponding experimental setups. We further demonstrate that our in silico RNA-Seq provides insights about hidden precursors that determine the final configuration of reads along gene bodies; enhancing or compensatory effects that explain apparently controversial observations can be observed. Moreover, our simulations identify hitherto unreported sources of systematic bias from RNA hydrolysis, a fragmentation technique currently employed by most RNA-Seq protocols.
Griebel T, Zacher B, Ribeca P, Raineri E, Lacroix V, Guigó R et al. Modelling and simulating generic RNA-Seq experiments with the flux simulator. Nucleic Acids Res. 2012; 40(20): 10073-83. DOI: 10.1093/nar/gks666
0305-1048
http://hdl.handle.net/10230/23100
http://dx.doi.org/10.1093/nar/gks666
Modelling and simulating generic RNA-Seq experiments with the flux simulator
oai:repositori.upf.edu:10230/231012020-06-17T07:42:45Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Mariotti, Marco, 1984-
author
Lobanov, Alexei V.
author
Guigó Serra, Roderic
author
Gladyshev, Vadim N.
author
2013
Selenoproteins are proteins containing an uncommon amino acid selenocysteine (Sec). Sec is inserted by a specific translational machinery that recognizes a stem-loop structure, the SECIS element, at the 3' UTR of selenoprotein genes and recodes a UGA codon within the coding sequence. As UGA is normally a translational stop signal, selenoproteins are generally misannotated and designated tools have to be developed for this class of proteins. Here, we present two new computational methods for selenoprotein identification and analysis, which we provide publicly through the web servers at http://gladyshevlab.org/SelenoproteinPredictionServer or http://seblastian.crg.es. SECISearch3 replaces its predecessor SECISearch as a tool for prediction of eukaryotic SECIS elements. Seblastian is a new method for selenoprotein gene detection that uses SECISearch3 and then predicts selenoprotein sequences encoded upstream of SECIS elements. Seblastian is able to both identify known selenoproteins and predict new selenoproteins. By applying these tools to diverse eukaryotic genomes, we provide a ranked list of newly predicted selenoproteins together with their annotated cysteine-containing homologues. An analysis of a representative candidate belonging to the AhpC family shows how the use of Sec in this protein evolved in bacterial and eukaryotic lineages.
Mariotti M, Lobanov AV, Guigo R, Gladyshev VN. SECISearch3 and Seblastian: new tools for prediction of SECIS elements and selenoproteins. Nucleic Acids Res. 2013;41(15):e149. DOI: 10.1093/nar/gkt550
0305-1048
http://hdl.handle.net/10230/23101
http://dx.doi.org/10.1093/nar/gkt550
SECISearch3 and Seblastian: new tools for prediction of SECIS elements and selenoproteins
oai:repositori.upf.edu:10230/231022020-06-17T07:48:26Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Romagné, Frédéric
author
Santesmasses Ruiz, Didac, 1978-
author
White, Louise
author
Sarangi, Gaurab K.
author
Mariotti, Marco, 1984-
author
Hübler, Ron
author
Weihmann, Antje
author
Parra Farré, Genís
author
Gladyshev, Vadim N.
author
Guigó Serra, Roderic
author
Castellano Hereza, Sergi
author
2014
SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are proteins that contain the amino acid selenocysteine (Sec) and the first release of the database included annotations for eight species. Since the release of SelenoDB 1.0 many new animal genomes have been sequenced. The annotations of selenoproteins in new genomes usually contain many errors in major databases. For this reason, we have now fully annotated selenoprotein genes in 58 animal genomes. We provide manually curated annotations for human selenoproteins, whereas we use an automatic annotation pipeline to annotate selenoprotein genes in other animal genomes. In addition, we annotate the homologous genes containing cysteine (Cys) instead of Sec. Finally, we have surveyed genetic variation in the annotated genes in humans. We use exon capture and resequencing approaches to identify single-nucleotide polymorphisms in more than 50 human populations around the world. We thus present a detailed view of the genetic divergence of Sec- and Cys-containing genes in animals and their diversity in humans. The addition of these datasets into the second release of the database provides a valuable resource for addressing medical and evolutionary questions in selenium biology.
Romagné F, Santesmasses D, White L, Sarangi GK, Mariotti M, Hübler R et al. SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans. Nucleic Acids Research. 2014;42(1):D437-43. DOI: 10.1093/nar/gkt1045
0305-1048
http://hdl.handle.net/10230/23102
http://dx.doi.org/10.1093/nar/gkt1045
SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans
oai:repositori.upf.edu:10230/231032020-06-17T07:51:47Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Nikolaou, Christoforos
author
Bermúdez, Ignacio
author
Manichanh, Chaysavanh
author
García Martínez, José
author
Guigó Serra, Roderic
author
Pérez Ortín, José E.
author
Roca, Joaquim
author
2013
Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly replicated chromosomes and the main relaxase of nucleosomal DNA. Apart from these general tasks, topo II participates in more specialized functions. In mammals, topo IIα interacts with specific RNA polymerases and chromatin-remodeling complexes, whereas topo IIβ regulates developmental genes in conjunction with chromatin remodeling and heterochromatin transitions. Here we show that in budding yeast, topo II regulates the expression of specific gene subsets. To uncover this, we carried out a genomic transcription run-on shortly after the thermal inactivation of topo II. We identified a modest number of genes not involved in the general stress response but strictly dependent on topo II. These genes present distinctive functional and structural traits in comparison with the genome average. Yeast topo II is a positive regulator of genes with well-defined promoter architecture that associates to chromatin remodeling complexes; it is a negative regulator of genes extremely hypo-acetylated with complex promoters and undefined nucleosome positioning, many of which are involved in polyamine transport. These findings indicate that yeast topo II operates on singular chromatin architectures to activate or repress DNA transcription and that this activity produces functional responses to ensure chromatin stability.
Nikolaou C, Bermúdez I, Manichanh C, García-Martinez J, Guigó R, Pérez-Ortín JE et al. Topoisomerase II regulates yeast genes with singular chromatin architectures. Nucleic Acids Res. 2013;41(20):9243-56. DOI: 10.1093/nar/gkt707
0305-1048
http://hdl.handle.net/10230/23103
http://dx.doi.org/10.1093/nar/gkt707
Topoisomerase II regulates yeast genes with singular chromatin architectures
oai:repositori.upf.edu:10230/231042020-06-17T07:54:47Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Durán, Elisa
author
Djebali, Sarah
author
González, Santi
author
Flores, Oscar
author
Mercader Bigas, Josep Maria
author
Guigó Serra, Roderic
author
Torrents, David
author
Soler López, Montserrat
author
Orozco, Modesto
author
2013
Although protein recognition of DNA motifs in promoter regions has been traditionally considered as a critical regulatory element in transcription, the location of promoters, and in particular transcription start sites (TSSs), still remains a challenge. Here we perform a comprehensive analysis of putative core promoter sequences relative to non-annotated predicted TSSs along the human genome, which were defined by distinct DNA physical properties implemented in our ProStar computational algorithm. A representative sampling of predicted regions was subjected to extensive experimental validation and analyses. Interestingly, the vast majority proved to be transcriptionally active despite the lack of specific sequence motifs, indicating that physical signaling is indeed able to detect promoter activity beyond conventional TSS prediction methods. Furthermore, highly active regions displayed typical chromatin features associated to promoters of housekeeping genes. Our results enable to redefine the promoter signatures and analyze the diversity, evolutionary conservation and dynamic regulation of human core promoters at large-scale. Moreover, the present study strongly supports the hypothesis of an ancient regulatory mechanism encoded by the intrinsic physical properties of the DNA that may contribute to the complexity of transcription regulation in the human genome.
Durán E, Djebali S, González S, Flores O, Mercader JM, Guigó R et al. Unravelling the hidden DNA structural/physical code provides novel insights on promoter location. Nucleic Acids Res. 2013;41(15):7220-30. DOI: 10.1093/nar/gkt511
0305-1048
http://hdl.handle.net/10230/23104
http://dx.doi.org/10.1093/nar/gkt511
Unravelling the hidden DNA structural/physical code provides novel insights on promoter location
oai:repositori.upf.edu:10230/231182020-06-17T07:57:05Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Janich, Peggy, 1981-
author
Toufighi, Kiana, 1980-
author
Solanas, Guiomar
author
Luis, Nuno Miguel, 1982-
author
Minkwitz, Susann
author
Serrano Pubull, Luis, 1982-
author
Lehner, Ben, 1978-
author
Aznar Benitah, Salvador
author
2013
Human skin copes with harmful environmental factors that are circadian in nature, yet how circadian rhythms modulate the function of human epidermal stem cells is mostly unknown. Here we show that in human epidermal stem cells and their differentiated counterparts, core clock genes peak in a successive and phased manner, establishing distinct temporal intervals during the 24 hr day period. Each of these successive clock waves is associated with a peak in the expression of subsets of transcripts that temporally segregate the predisposition of epidermal stem cells to respond to cues that regulate their proliferation or differentiation, such as TGFβ and calcium. Accordingly, circadian arrhythmia profoundly affects stem cell function in culture and in vivo. We hypothesize that this intricate mechanism ensures homeostasis by providing epidermal stem cells with environmentally relevant temporal functional cues during the course of the day and that its perturbation may contribute to aging and carcinogenesis.
Janich P, Toufighi K, Solanas G, Luis NM, Minkwitz S, Serrano L et al. Human epidermal stem cell function is regulated by circadian oscillations. Cell Stem Cell. 2013;13(6):745-53. DOI: 10.1016/j.stem.2013.09.004
1934-5909
http://hdl.handle.net/10230/23118
http://dx.doi.org/10.1016/j.stem.2013.09.004
Human epidermal stem cell function is regulated by circadian oscillations
oai:repositori.upf.edu:10230/231192021-04-13T10:07:10Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Lamond, Angus I.
author
Uhlen, Mathias
author
Horning, Stevan
author
Makarov, Alexander
author
Robinson, Carol V.
author
Serrano Pubull, Luis, 1982-
author
Hartl, F. Ulrich
author
Baumeister, Wolfgang
author
Werenskiold, Anne Katrin
author
Andersen, Jens S.
author
Vorm, Ole
author
Linial, Michal
author
Aebersold, Ruedi
author
Mann, Matthias
author
2012
The term "proteomics" encompasses the large-scale detection and analysis of proteins and their post-translational modifications. Driven by major improvements in mass spectrometric instrumentation, methodology, and data analysis, the proteomics field has burgeoned in recent years. It now provides a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16 research papers reporting major recent progress by the PROSPECTS groups, including improvements to the resolution and sensitivity of the Orbitrap family of mass spectrometers, systematic detection of proteins using highly characterized antibody collections, and new methods for absolute as well as relative quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how the proteomics field is moving beyond simply identifying proteins with high sensitivity toward providing a powerful and versatile set of assay systems for characterizing proteome dynamics and thereby creating a new "third generation" proteomics strategy that offers an indispensible tool for cell biology and molecular medicine.
Lamond AI, Uhlen M, Horning S, Makarov A, Robinson CV, Serrano L et al. Advancing cell biology through proteomics in space and time (PROSPECTS). Mol Cell Proteomics. 2012; 11(3): O112.017731. DOI: 10.1074/mcp.O112.017731
1535-9476
http://hdl.handle.net/10230/23119
http://dx.doi.org/10.1074/mcp.O112.017731
Advancing cell biology through proteomics in space and time (PROSPECTS)
oai:repositori.upf.edu:10230/231202021-04-13T10:08:52Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Szegezdi, Eva
author
van der Sloot, Almer M.
author
Mahalingam, Devalingam
author
O'Leary, Lynda
author
Cool, Robbert H.
author
Muñoz, Inés G.
author
Montoya, Guillermo
author
Quax, Wim J.
author
Jong, Steven M. de, 1962-
author
Samali, Afshin
author
Serrano Pubull, Luis, 1982-
author
2012
Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ligands can trigger the formation of nonproductive receptor complexes, which slows down the formation of active receptor complexes and thus can block signal transduction. Our model predicts that increasing the receptor specificity of the ligand without changing its binding parameters should result in faster receptor activation and enhanced signaling. We experimentally validated this hypothesis using the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its four membrane-bound receptors as an example. Bypassing ligand-induced receptor hetero-oligomerization by receptor-selective TRAIL variants enhanced the kinetics of receptor activation and augmented apoptosis. Our results suggest that control of signaling pathways by promiscuous ligands could result in apparent slow biological kinetics and blocking signal transmission. By modulating the relative amount of the different receptors for the ligand, signaling processes like apoptosis can be accelerated or decelerated and even inhibited. It also implies that more effective treatments using protein therapeutics could be achieved simply by altering specificity.
Szegezdi E, van der Sloot AM, Mahalingam D, O'Leary L, Cool RH, Muñoz IG et al. Kinetics in signal transduction pathways involving promiscuous oligomerizing receptors can be determined by receptor specificity: apoptosis induction by TRAIL. Mol Cell Proteomics. 2012; 11(3): M111.013730. DOI: 10.1074/mcp.M111.013730
1535-9476
http://hdl.handle.net/10230/23120
http://dx.doi.org/10.1074/mcp.M111.013730
Kinetics in signal transduction pathways involving promiscuous oligomerizing receptors can be determined by receptor specificity: apoptosis induction by TRAIL
oai:repositori.upf.edu:10230/231212020-06-17T08:10:08Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Kiel, Christina
author
Serrano Pubull, Luis, 1982-
author
2012
In recent years, high-throughput discovery of macromolecular protein structures and complexes has played a major role in advancing a more systems-oriented view of protein interaction and signaling networks. The design of biological systems often employs structural information or structure-based protein design to successfully implement synthetic signaling circuits or for rewiring signaling flows. Here, we summarize the latest advances in using structural information for studying protein interaction and signaling networks, and in synthetic biology approaches. We then provide a perspective of how combining structural biology with engineered cell signaling modules--using additional information from quantitative biochemistry and proteomics, gene evolution, and mathematical modeling--can provide insight into signaling modules and the general design principles of cell signaling. Ultimately, this will improve our understanding of cell- and tissue-type-specific signal transduction. Integrating the quantitative effects of disease mutations into these systems may provide a basis for elucidating the molecular mechanisms of diseases.
Kiel C, Serrano L. Structural data in synthetic biology approaches for studying general design principles of cellular signaling networks. Structure. 2012;20(11):1806-13. DOI: 10.1016/j.str.2012.10.002
0969-2126
http://hdl.handle.net/10230/23121
http://dx.doi.org/10.1016/j.str.2012.10.002
Structural data in synthetic biology approaches for studying general design principles of cellular signaling networks
oai:repositori.upf.edu:10230/231222020-06-17T08:14:18Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_8581col_10230_6238
00925njm 22002777a 4500
dc
Verschueren, Erik
author
Vanhee, Peter
author
Rousseau, Frédéric
author
Schymkowitz, Joost
author
Serrano Pubull, Luis, 1982-
author
2013
The number of protein-peptide interactions in a cell is so large that experimental determination of all these complex structures would be a daunting task. Although homology modeling and refinement protocols have vastly improved the number and quality of predicted structural models, ab initio methods are still challenged by both the large number of possible docking sites and the conformational space accessible to flexible peptides. We present a method that addresses these challenges by sampling the entire accessible surface of a protein with a reduced conformational space of interacting backbone fragment pairs from unrelated structures. We demonstrate its potential by predicting ab initio the bound structure for a variety of protein-peptide complexes. In addition, we show the potential of our method for the discovery of domain interaction sites and domain-domain docking.
Verschueren E, Vanhee P, Rousseau F, Schymkowitz J, Serrano L. Protein-peptide complex prediction through fragment interaction patterns. Structure. 2013;21(5):789-97. DOI: 10.1016/j.str.2013.02.023
0969-2126
http://hdl.handle.net/10230/23122
http://dx.doi.org/10.1016/j.str.2013.02.023
Protein-peptide complex prediction through fragment interaction patterns
oai:repositori.upf.edu:10230/231782018-01-24T08:07:12Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Silva, Larissa Lopes
author
Marcet Houben, Marina
author
Alves Nahum, Laila
author
Zerlotini, Adhemar
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Oliveira, Guilherme
author
2012
Background: Schistosoma mansoni is one of the causative agents of schistosomiasis, a neglected tropical disease that affects about 237 million people worldwide. Despite recent efforts, we still lack a general understanding of the relevant host-parasite interactions, and the possible treatments are limited by the emergence of resistant strains and the absence of a vaccine. The S. mansoni genome was completely sequenced and still under continuous annotation. Nevertheless, more than 45% of the encoded proteins remain without experimental characterization or even functional prediction. To improve our knowledge regarding the biology of this parasite, we conducted a proteome-wide evolutionary analysis to provide a broad view of the S. mansoni’s proteome evolution and to improve its functional annotation. Results: Using a phylogenomic approach, we reconstructed the S. mansoni phylome, which comprises the evolutionary histories of all parasite proteins and their homologs across 12 other organisms. The analysis of a total of 7,964 phylogenies allowed a deeper understanding of genomic complexity and evolutionary adaptations to a parasitic lifestyle. In particular, the identification of lineage-specific gene duplications pointed to the diversification of several protein families that are relevant for host-parasite interaction, including proteases, tetraspanins, fucosyltransferases, venom allergen-like proteins, and tegumental-allergen-like proteins. In addition to the evolutionary knowledge, the phylome data enabled us to automatically re-annotate 3,451 proteins through a phylogenetic-based approach rather than solely sequence similarity searches. To allow further exploitation of this valuable data, all information has been made available at PhylomeDB (http://www.phylomedb.org webcite). Conclusions: In this study, we used an evolutionary approach to assess S. mansoni parasite biology, improve genome/proteome functional annotation, and provide insights into host-parasite interactions. Taking advantage of a proteome-wide perspective rather than focusing on individual proteins, we identified that this parasite has experienced specific gene duplication events, particularly affecting genes that are potentially related to the parasitic lifestyle. These innovations may be related to the mechanisms that protect S. mansoni against host immune responses being important adaptations for the parasite survival in a potentially hostile environment. Continuing this work, a comparative analysis involving genomic, transcriptomic, and proteomic data from other helminth parasites, other parasites, and vectors will supply more information regarding parasite’s biology as well as host-parasite interactions.
Silva LL, Marcet-Houben M, Nahum LA, Zerlotini A, Gabaldón T, Oliveira G. The schistosoma mansoni phylome: using evolutionary genomics to gain insight into a parasite's biology. BMC Genomics. 2012; 13: 617. DOI 10.1186/1471-2164-13-617
1471-2164
http://hdl.handle.net/10230/23178
http://dx.doi.org/10.1186/1471-2164-13-617
The schistosoma mansoni phylome: using evolutionary genomics to gain insight into a parasite's biology
oai:repositori.upf.edu:10230/231792018-01-24T08:07:27Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Marcet Houben, Marina
author
Ballester, Ana Rosa
author
de la Fuente, Beatriz
author
Harries, Eleonora
author
Marcos del Águila, Josep, 1971-
author
González Candelas, Luis
author
Gabaldón Estevan, Juan Antonio, 1973-
author
2012
Background: Penicillium digitatum is a fungal necrotroph causing a common citrus postharvest disease known as green mold. In order to gain insight into the genetic bases of its virulence mechanisms and its high degree of host-specificity, the genomes of two P. digitatum strains that differ in their antifungal resistance traits have been sequenced and compared with those of 28 other Pezizomycotina. Results: The two sequenced genomes are highly similar, but important differences between them include the presence of a unique gene cluster in the resistant strain, and mutations previously shown to confer fungicide resistance. The two strains, which were isolated in Spain, and another isolated in China have identical mitochondrial genome sequences suggesting a recent worldwide expansion of the species. Comparison with the closely-related but non-phytopathogenic P. chrysogenum reveals a much smaller gene content in P. digitatum, consistent with a more specialized lifestyle. We show that large regions of the P. chrysogenum genome, including entire supercontigs, are absent from P. digitatum, and that this is the result of large gene family expansions rather than acquisition through horizontal gene transfer. Our analysis of the P. digitatum genome is indicative of heterothallic sexual reproduction and reveals the molecular basis for the inability of this species to assimilate nitrate or produce the metabolites patulin and penicillin. Finally, we identify the predicted secretome, which provides a first approximation to the protein repertoire used during invasive growth. Conclusions: The complete genome of P. digitatum, the first of a phytopathogenic Penicillium species, is a valuable tool for understanding the virulence mechanisms and host-specificity of this economically important pest.
Marcet-Houben M, Ballester AR, de la Fuente B, Harries E, Marcos JF, González-Candelas L et al. Genome sequence of the necrotrophic fungus Penicillium digitatum, the main postharvest pathogen of citrus. BMC Genomics. 2012; 13: 646. DOI 10.1186/1471-2164-13-646
1471-2164
http://hdl.handle.net/10230/23179
http://dx.doi.org/10.1186/1471-2164-13-646
Genome sequence of the necrotrophic fungus Penicillium digitatum, the main postharvest pathogen of citrus
oai:repositori.upf.edu:10230/231802021-04-13T10:38:01Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Llorens, Franc
author
Bañez Coronel, Mónica
author
Pantano Rubiño, Lorena, 1982-
author
del Río, José Antonio
author
Ferrer, Isidre
author
Estivill, Xavier, 1955-
author
Martí, Eulàlia
author
2013
Background: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101). Results: The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101. Conclusions: These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.
Llorens F, Bañez-Coronel M, Pantano L, del Río JA, Ferrer I, Estivill X, Martí E. A highly expressed miR-101 isomiR is a functional silencing small RNA. BMC Genomics. 2013; 14: 104. DOI 10.1186/1471-2164-14-104
1471-2164
http://hdl.handle.net/10230/23180
http://dx.doi.org/10.1186/1471-2164-14-104
A highly expressed miR-101 isomiR is a functional silencing small RNA
oai:repositori.upf.edu:10230/231952018-01-24T08:06:50Zcom_10230_20545com_10230_5542com_10230_20719com_10230_23115col_10230_22227col_10230_22498col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Bassaganyas Bars, Laia, 1985-
author
Riveira Muñoz, Eva
author
García Aragonés, Manel
author
González Ruiz, Juan Ramón
author
Cáceres Aguilar, Mario
author
Armengol i Dulcet, Lluís
author
Estivill, Xavier, 1955-
author
2013
Background: There is increasing evidence of the importance of copy number variants (CNV) in genetic diversity among individuals and populations, as well as in some common genetic diseases. We previously characterized a common 32-kb insertion/deletion variant of the PSORS4 locus at chromosome 1q21 that harbours the LCE3C and LCE3B genes. This variant allele (LCE3C_LCE3B-del) is common in patients with psoriasis and other autoimmune disorders from certain ethnic groups./nResults: Using array-CGH (Agilent 244 K) in samples from the HapMap and Human Genome Diversity Panel (HGDP) collections, we identified 54 regions showing population differences in comparison to Africans. We provided here a comprehensive population-genetic analysis of one of these regions, which involves the 32-kb deletion of the PSORS4 locus. By a PCR-based genotyping assay we characterised the profiles of the LCE3C_LCE3B-del and the linkage disequilibrium (LD) pattern between the variant allele and the tag SNP rs4112788. Our results show that most populations tend to have a higher frequency of the deleted allele than Sub-Saharan Africans. Furthermore, we found strong LD between rs4112788G and LCE3C_LCE3B-del in most non-African populations (r2 >0.8), in contrast to the low concordance between loci (r2 <0.3) in the African populations. Conclusions: These results are another example of population variability in terms of biomedical interesting CNV. The frequency distribution of the LCE3C_LCE3B-del allele and the LD pattern across populations suggest that the differences between ethnic groups might not be due to natural selection, but the consequence of genetic drift caused by the strong bottleneck that occurred during “out of Africa” expansion.
Bassaganyas L, Riveira-Muñoz E, García-Aragonés M, González JR, Cáceres M, Armengol L et al. Worldwide population distribution of the common LCE3C-LCE3B deletion associated with psoriasis and other autoimmune disorders. BMC Genomics. 2013; 14: 261. DOI 10.1186/1471-2164-14-261
1471-2164
http://hdl.handle.net/10230/23195
http://dx.doi.org/10.1186/1471-2164-14-261
Worldwide population distribution of the common LCE3C-LCE3B deletion associated with psoriasis and other autoimmune disorders
oai:repositori.upf.edu:10230/231962019-04-08T15:22:57Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Llorens, Franc
author
Hummel, Manuela
author
Pantano Rubiño, Lorena, 1982-
author
Pastor, Xavier
author
Vivancos Prellezo, Ana
author
Castillo Andreo, Esther
author
Mattlin, Heidi
author
Ferrer Admetlla, Anna
author
Ingham, Matthew
author
Noguera, Marc
author
Kofler, Robert
author
Dohm, Juliane C.
author
Pluvinet, Raquel
author
Bayés, Mònica
author
Himmelbauer, Heinz
author
del Río, José Antonio
author
Martí, Eulàlia
author
Sumoy Van Dyck, Lauro
author
2013
Background: Epidermal Growth Factor (EGF) plays an important function in the regulation of cell growth, proliferation, and differentiation by binding to its receptor (EGFR) and providing cancer cells with increased survival responsiveness. Signal transduction carried out by EGF has been extensively studied at both transcriptional and post-transcriptional levels. Little is known about the involvement of microRNAs (miRNAs) in the EGF signaling pathway. miRNAs have emerged as major players in the complex networks of gene regulation, and cancer miRNA expression studies have evidenced a direct involvement of miRNAs in cancer progression. Results: In this study, we have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by reverse transcription quantitative PCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomiRs) among regulated miRNAs. Conclusions: We propose that the use of global genomic miRNA cross-validation derived from high throughput technologies can be used to generate more reliable datasets inferring more robust networks of co-regulated predicted miRNA target genes.
Llorens F, Hummel M, Pantano L, Pastor X, Vivancos A, Castillo E, Mattlin H, Ferrer A, Ingham M, Noguera M, Kofler R, Dohm JC, Pluvinet R, Bayés M, Himmelbauer H, del Rio JA, Martí E, Sumoy L. Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor. BMC Genomics. 2013; 14: 371. DOI 10.1186/1471-2164-14-371
1471-2164
http://hdl.handle.net/10230/23196
http://dx.doi.org/10.1186/1471-2164-14-371
Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor
oai:repositori.upf.edu:10230/231972018-01-24T08:31:13Zcom_10230_20545com_10230_5542com_10230_23115col_10230_22227col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Aigner, Johanna, 1981-
author
Villatoro, Sergi
author
Rabionet, Raquel
author
Roquer, Jaume
author
Jiménez Conde, Jordi
author
Martí, Eulàlia
author
Estivill, Xavier, 1955-
author
2013
Background: The Butyrophilin-like (BTNL) proteins are likely to play an important role in inflammation and immune response. Like the B7 protein family, many human and murine BTNL members have been shown to control T lymphocytes response, and polymorphisms in human BTNL2 have been linked to several inflammatory diseases, such as pulmonary sarcoidosis, inflammatory bowel disease and neonatal lupus. Results: In this study we provide a comprehensive population, genomic and transcriptomic analysis of a 56-kb deletion copy number variant (CNV), located within two segmental duplications of two genes belonging to the BTNL family, namely BTNL8 and BTNL3. We confirm the presence of a novel BTNL8*3 fusion-protein product, and show an influence of the deletion variant on the expression level of several genes involved in immune function, including BTNL9, another member of the same family. Moreover, by genotyping HapMap and human diversity panel (HGDP) samples, we demonstrate a clear difference in the stratification of the BTNL8_BTNL3-del allele frequency between major continental human populations. Conclusion: Despite tremendous progress in the field of structural variation, rather few CNVs have been functionally characterized so far. Here, we show clear functional consequences of a new deletion CNV (BTNL8_BTNL3-del) with potentially important implication in the human immune system and in inflammatory and proliferative disorders. In addition, the marked population differences found of BTNL8_BTNL3-del frequencies suggest that this deletion CNV might have evolved under positive selection due to environmental conditions in some populations, with potential phenotypic consequences.
Aigner J, Villatoro S, Rabionet R, Roquer J, Jiménez-Conde J, Martí E, Estivill X. A common 56-kilobase deletion in a primate-specific segmental duplication creates a novel butyrophilin-like protein. BMC Genetics. 2013; 14: 61. DOI 10.1186/1471-2156-14-61
1471-2156
http://hdl.handle.net/10230/23197
http://dx.doi.org/10.1186/1471-2156-14-61
A common 56-kilobase deletion in a primate-specific segmental duplication creates a novel butyrophilin-like protein
oai:repositori.upf.edu:10230/232042020-06-17T08:42:21Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Degenkolbe, Elisa
author
König, Jana
author
Zimmer, Julia
author
Walther, Maria
author
Reißner, Carsten
author
Nickel, Joachim
author
Plöger, Frank
author
Raspopovic, Jelena, 1984-
author
Sharpe, James
author
Dathe, Katarina
author
Hecht, Jacqueline T.
author
Mundlos, Stefan
author
Doelken, Sandra C.
author
Seemann, Petra
author
2013
Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5(W414R) variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain- and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA.
Degenkolbe E, König J, Zimmer J, Walther M, Reißner C, Nickel J et al. GDF5 point mutation strikes twice--causing BDA1 and SYNS2. PLoS Genet. 2013;9(10):e1003846. DOI: 10.1371/journal.pgen.1003846
1553-7390
http://hdl.handle.net/10230/23204
http://dx.doi.org/10.1371/journal.pgen.1003846
GDF5 point mutation strikes twice--causing BDA1 and SYNS2
oai:repositori.upf.edu:10230/232132020-06-17T08:43:30Zcom_10230_6237com_10230_5542com_10230_20545com_10230_20719com_10230_23115col_10230_6238col_10230_22227col_10230_22498col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Esnaola, Mikel
author
Puig, Pedro
author
González, David
author
Castelo Valdueza, Robert
author
González Ruiz, Juan Ramón
author
2013
Background: High-throughput RNA sequencing (RNA-seq) offers unprecedented power to capture the real dynamics of gene expression. Experimental designs with extensive biological replication present a unique opportunity to exploit this feature and distinguish expression profiles with higher resolution. RNA-seq data analysis methods so far have been mostly applied to data sets with few replicates and their default settings try to provide the best performance under this constraint. These methods are based on two well-known count data distributions: the Poisson and the negative binomial. The way to properly calibrate them with large RNA-seq data sets is not trivial for the non-expert bioinformatics user. Results: Here we show that expression profiles produced by extensively-replicated RNA-seq experiments lead to a rich diversity of count data distributions beyond the Poisson and the negative binomial, such as Poisson-Inverse Gaussian or Pólya-Aeppli, which can be captured by a more general family of count data distributions called the Poisson-Tweedie. The flexibility of the Poisson-Tweedie family enables a direct fitting of emerging features of large expression profiles, such as heavy-tails or zero-inflation, without the need to alter a single configuration parameter. We provide a software package for R called tweeDEseq implementing a new test for differential expression based on the Poisson-Tweedie family. Using simulations on synthetic and real RNA-seq data we show that tweeDEseq yields P-values that are equally or more accurate than competing methods under different configuration parameters. By surveying the tiny fraction of sex-specific gene expression changes in human lymphoblastoid cell lines, we also show that tweeDEseq accurately detects differentially expressed genes in a real large RNA-seq data set with improved performance and reproducibility over the previously compared methodologies. Finally, we compared the results with those obtained from microarrays in order to check for reproducibility. Conclusions: RNA-seq data with many replicates leads to a handful of count data distributions which can be accurately estimated with the statistical model illustrated in this paper. This method provides a better fit to the underlying biological variability; this may be critical when comparing groups of RNA-seq samples with markedly different count data distributions. The tweeDEseq package forms part of the Bioconductor project and it is available for download at http://www.bioconductor.org webcite.
Esnaola M, Puig P, Gonzalez D, Castelo R, Gonzalez JR. A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments. BMC Bioinformatics. 2013;14:254. DOI 10.1186/1471-2105-14-254
1471-2105
http://hdl.handle.net/10230/23213
http://dx.doi.org/10.1186/1471-2105-14-254
A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments
oai:repositori.upf.edu:10230/232192018-01-24T08:09:22Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Janssens, Hilde
author
Siggens, Ken
author
Cicin Sain, Damjan
author
Jiménez Guri, Eva
author
Musy, Marco
author
Akam, Michael
author
Jaeger, Johannes, 1973-
author
2014
Background: Comparative studies of developmental processes are one of the main approaches to evolutionary developmental biology (evo-devo). Over recent years, there has been a shift of focus from the comparative study of particular regulatory genes to the level of whole gene networks. Reverse-engineering methods can be used to computationally reconstitute and analyze the function and dynamics of such networks. These methods require quantitative spatio-temporal expression data for model fitting. Obtaining such data in non-model organisms remains a major technical challenge, impeding the wider application of data-driven mathematical modeling to evo-devo. Results: We have raised antibodies against four segmentation gene products in the moth midge Clogmia albipunctata, a non-drosophilid dipteran species. We have used these antibodies to create a quantitative atlas of protein expression patterns for the gap gene hunchback (hb), and the pair-rule gene even-skipped (eve). Our data reveal differences in the dynamics of Hb boundary positioning and Eve stripe formation between C. albipunctata and Drosophila melanogaster. Despite these differences, the overall relative spatial arrangement of Hb and Eve domains is remarkably conserved between these two distantly related dipteran species. Conclusions: We provide a proof of principle that it is possible to acquire quantitative gene expression data at high accuracy and spatio-temporal resolution in non-model organisms. Our quantitative data extend earlier qualitative studies of segmentation gene expression in C. albipunctata, and provide a starting point for comparative reverse-engineering studies of the evolutionary and developmental dynamics of the segmentation gene system.
Janssens H, Siggens K, Cicin-Sain D, Jiménez-Guri E, Musy M, Akam M, Jaeger J. A quantitative atlas of Even-skipped and Hunchback expression in Clogmia albipunctata (Diptera: Psychodidae) blastoderm embryos. EvoDevo. 2014; 5: 1. DOI 10.1186/2041-9139-5-1
2041-9139
http://hdl.handle.net/10230/23219
http://dx.doi.org/10.1186/2041-9139-5-1
A quantitative atlas of Even-skipped and Hunchback expression in Clogmia albipunctata (Diptera: Psychodidae) blastoderm embryos
oai:repositori.upf.edu:10230/232232018-01-24T08:07:56Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Tartaglia, Gian Gaetano
author
Cirillo, Davide
author
Marchese, Domenica, 1986-
author
Agostini, Federico, 1985-
author
Livi, Carmen Maria
author
Botta Orfila, Teresa
author
2014
Background: RNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs. Recent studies have reported that an unexpectedly large number of proteins are able to interact with RNA, but the partners of many RNA-binding proteins are still uncharacterized. Results: We combined prediction of ribonucleoprotein interactions, based on catRAPID calculations, with analysis of protein and RNA expression profiles from human tissues. We found strong interaction propensities for both positively and negatively correlated expression patterns. Our integration of in silico and ex vivo data unraveled two major types of protein–RNA interactions, with positively correlated patterns related to cell cycle control and negatively correlated patterns related to survival, growth and differentiation. To facilitate the investigation of protein–RNA interactions and expression networks, we developed the catRAPID express web server. Conclusions: Our analysis sheds light on the role of RNA-binding proteins in regulating proliferation and differentiation processes, and we provide a data exploration tool to aid future experimental studies.
Cirillo D, Marchese D, Agostini F, Livi CM, Botta-Orfila T, Tartaglia GG. Constitutive patterns of gene expression regulated by RNA-binding proteins. Genome Biology. 2014; 15: R13. DOI 10.1186/gb-2014-15-1-r13
1465-6906
http://hdl.handle.net/10230/23223
http://dx.doi.org/10.1186/gb-2014-15-1-r13
Constitutive patterns of gene expression regulated by RNA-binding proteins
oai:repositori.upf.edu:10230/232242018-01-24T08:08:25Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Elsik, Christine G
author
Cámara, Francisco
author
Honey Bee Genome Sequencing Consortium
author
2014
Background: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. Results: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes 5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. Conclusions: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.
Elsik CG, Worley KC, Bennett AK, Beye M, Camara F, Childers CP et al. Finding the missing honey bee genes: lessons learned from a genome upgrade. BMC Genomics. 2014; 15: 86. DOI 10.1186/1471-2164-15-86
1471-2164
http://hdl.handle.net/10230/23224
http://dx.doi.org/10.1186/1471-2164-15-86
Finding the missing honey bee genes: lessons learned from a genome upgrade
oai:repositori.upf.edu:10230/232252018-01-24T08:08:41Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Krisko, Anita
author
Copic, Tea
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Lehner, Ben, 1978-
author
Supek, Fran
author
2014
Background: The genetic code is redundant, meaning that most amino acids can be encoded by more than one codon. Highly expressed genes tend to use optimal codons to increase the accuracy and speed of translation. Thus, codon usage biases provide a signature of the relative expression levels of genes, which can, uniquely, be quantified across the domains of life. Results: Here we describe a general statistical framework to exploit this phenomenon and to systematically associate genes with environments and phenotypic traits through changes in codon adaptation. By inferring evolutionary signatures of translation efficiency in 911 bacterial and archaeal genomes while controlling for confounding effects of phylogeny and inter-correlated phenotypes, we linked 187 gene families to 24 diverse phenotypic traits. A series of experiments in Escherichia coli revealed that 13 of 15, 19 of 23, and 3 of 6 gene families with changes in codon adaptation in aerotolerant, thermophilic, or halophilic microbes. Respectively, confer specific resistance to, respectively, hydrogen peroxide, heat, and high salinity. Further, we demonstrate experimentally that changes in codon optimality alone are sufficient to enhance stress resistance. Finally, we present evidence that multiple genes with altered codon optimality in aerobes confer oxidative stress resistance by controlling the levels of iron and NAD(P)H. Conclusions: Taken together, these results provide experimental evidence for a widespread connection between changes in translation efficiency and phenotypic adaptation. As the number of sequenced genomes increases, this novel genomic context method for linking genes to phenotypes based on sequence alone will become increasingly useful.
Krisko A, Copic T, Gabaldón T, Lehner B, Supek F. Inferring gene function from evolutionary change in signatures of translation efficiency. Genome Biology. 2014; 15: R44. DOI 10.1186/gb-2014-15-3-r44
1465-6906
http://hdl.handle.net/10230/23225
http://dx.doi.org/10.1186/gb-2014-15-3-r44
Inferring gene function from evolutionary change in signatures of translation efficiency
oai:repositori.upf.edu:10230/232262019-02-07T11:54:41Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Verd Fernández, Berta, 1984-
author
Crombach, Anton
author
Jaeger, Johannes, 1973-
author
2014
Background: Waddington’s epigenetic landscape is an intuitive metaphor for the developmental and evolutionary potential of biological regulatory processes. It emphasises time-dependence and transient behaviour. Nowadays, we can derive this landscape by modelling a specific regulatory network as a dynamical system and calculating its so-called potential surface. In this sense, potential surfaces are the mathematical equivalent of the Waddingtonian landscape metaphor. In order to fully capture the time-dependent (non-autonomous) transient behaviour of biological processes, we must be able to characterise potential landscapes and how they change over time. However, currently available mathematical tools focus on the asymptotic (steady-state) behaviour of autonomous dynamical systems, which restricts how biological systems are studied. Results: We present a pragmatic first step towards a methodology for dealing with transient behaviours in non-autonomous systems. We propose a classification scheme for different kinds of such dynamics based on the simulation of a simple genetic toggle-switch model with time-variable parameters. For this low-dimensional system, we can calculate and explicitly visualise numerical approximations to the potential landscape. Focussing on transient dynamics in non-autonomous systems reveals a range of interesting and biologically relevant behaviours that would be missed in steady-state analyses of autonomous systems. Our simulation-based approach allows us to identify four qualitatively different kinds of dynamics: transitions, pursuits, and two kinds of captures. We describe these in detail, and illustrate the usefulness of our classification scheme by providing a number of examples that demonstrate how it can be employed to gain specific mechanistic insights into the dynamics of gene regulation. Conclusions: The practical aim of our proposed classification scheme is to make the analysis of explicitly time-dependent transient behaviour tractable, and to encourage the wider use of non-autonomous models in systems biology. Our method is applicable to a large class of biological processes.
Verd B, Crombach A, Jaeger J. Classification of transient behaviours in a time-dependent toggle switch model. BMC Systems Biology. 2014; 8: 43. DOI 10.1186/1752-0509-8-43
1752-0509
http://hdl.handle.net/10230/23226
http://dx.doi.org/10.1186/1752-0509-8-43
Classification of transient behaviours in a time-dependent toggle switch model
oai:repositori.upf.edu:10230/232272024-01-29T12:44:14Zcom_10230_20545com_10230_5542com_10230_23115col_10230_22227col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Friedländer, Marc R.
author
Lizano González, Esther, 1974-
author
Houben, Anna J.
author
Bezdan, Daniela
author
Bañez Coronel, Mónica
author
Kudla, Grzegorz
author
Mateu Huertas, Elisabet, 1983-
author
Kagerbauer, Birgit
author
González Morilla, Justo
author
Chen, Kevin C
author
LeProust, Emily M
author
Martí Puig, Eulàlia
author
Estivill, Xavier, 1955-
author
2014
Background: MicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome. Results: Employing an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling, we devised a quantitative miRNA capture system. In a kidney cell system, 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain. Conclusions: In summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.
Friedländer MR, Lizano E, Houben AJ, Bezdan D, Báñez-Coronel M, Kudla G, Mateu-Huertas E, Kagerbauer B, González J, Chen KC, LeProust EM, Martí E, Estivill X. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biology. 2014; 15: R57. DOI 10.1186/gb-2014-15-4-r57
1465-6906
http://hdl.handle.net/10230/23227
http://dx.doi.org/10.1186/gb-2014-15-4-r57
Evidence for the biogenesis of more than 1,000 novel human microRNAs
oai:repositori.upf.edu:10230/232422018-01-24T08:08:44Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Kunze, Gotthard
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Marcet Houben, Marina
author
Neuvéglise, Cécile
author
2014
Background: The industrially important yeast Blastobotrys (Arxula) adeninivorans is an asexual hemiascomycete phylogenetically very distant from Saccharomyces cerevisiae. Its unusual metabolic flexibility allows it to use a wide range of carbon and nitrogen sources, while being thermotolerant, xerotolerant and osmotolerant./nResults: The sequencing of strain LS3 revealed that the nuclear genome of A. adeninivorans is 11.8 Mb long and consists of four chromosomes with regional centromeres. Its closest sequenced relative is Yarrowia lipolytica, although mean conservation of orthologs is low. With 914 introns within 6116 genes, A. adeninivorans is one of the most intron-rich hemiascomycetes sequenced to date. Several large species-specific families appear to result from multiple rounds of segmental duplications of tandem gene arrays, a novel mechanism not yet described in yeasts. An analysis of the genome and its transcriptome revealed enzymes with biotechnological potential, such as two extracellular tannases (Atan1p and Atan2p) of the tannic-acid catabolic route, and a new pathway for the assimilation of n-butanol via butyric aldehyde and butyric acid. Conclusions: The high-quality genome of this species that diverged early in Saccharomycotina will allow further fundamental studies on comparative genomics, evolution and phylogenetics. Protein components of different pathways for carbon and nitrogen source utilization were identified, which so far has remained unexplored in yeast, offering clues for further biotechnological developments. In the course of identifying alternative microorganisms for biotechnological interest, A. adeninivorans has already proved its strengthened competitiveness as a promising cell factory for many more applications.
Kunze G, Gaillardin C, Czernicka M, Durrens P, Martin T, Böer E, Gabaldón T et al. The complete genome of Blastobotrys (Arxula) adeninivorans LS3 - a yeast of biotechnological interest. Biotechnology for Biofuels. 2014; 7: 66. DOI 10.1186/1754-6834-7-66
1754-6834
http://hdl.handle.net/10230/23242
http://dx.doi.org/10.1186/1754-6834-7-66
The complete genome of Blastobotrys (Arxula) adeninivorans LS3 - a yeast of biotechnological interest.
oai:repositori.upf.edu:10230/232432018-01-24T08:09:00Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Livi, Carmen Maria
author
Blanzieri, Enrico
author
2014
Background: RNA-binding proteins interact with specific RNA molecules to regulate important cellular processes. It is therefore necessary to identify the RNA interaction partners in order to understand the precise functions of such proteins. Protein-RNA interactions are typically characterized using in vivo and in vitro experiments but these may not detect all binding partners. Therefore, computational methods that capture the protein-dependent nature of such binding interactions could help to predict potential binding partners in silico. Results: We have developed three methods to predict whether an RNA can interact with a particular RNA-binding protein using support vector machines and different features based on the sequence (the Oli method), the motif score (the OliMo method) and the secondary structure (the OliMoSS method). We applied these approaches to different experimentally-derived datasets and compared the predictions with RNAcontext and RPISeq. Oli outperformed OliMoSS and RPISeq, confirming our protein-specific predictions and suggesting that tetranucleotide frequencies are appropriate discriminative features. Oli and RNAcontext were the most competitive methods in terms of the area under curve. A precision-recall curve analysis achieved higher precision values for Oli. On a second experimental dataset including real negative binding information, Oli outperformed RNAcontext with a precision of 0.73 vs. 0.59. Conclusions: Our experiments showed that features based on primary sequence information are sufficiently discriminating to predict specific RNA-protein interactions. Sequence motifs and secondary structure information were not necessary to improve these predictions. Finally we confirmed that protein-specific experimental data concerning RNA-protein interactions are valuable sources of information that can be used for the efficient training of models for in silico predictions. The scripts are available upon request to the corresponding author.
Livi CM, Blanzieri E. Protein-specific prediction of mRNA binding using RNA sequences, binding motifs and predicted secondary structures. BMC Bioinformatics. 2014; 15: 123. DOI 10.1186/1471-2105-15-123
1471-2105
http://hdl.handle.net/10230/23243
http://dx.doi.org/10.1186/1471-2105-15-123
Protein-specific prediction of mRNA binding using RNA sequences, binding motifs and predicted secondary structures
oai:repositori.upf.edu:10230/232442018-01-24T08:09:12Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Aguilar, Helena
author
Caizzi, Livia
author
Di Croce, Luciano
author
Pujana, Miguel Angel
author
2014
Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERα transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process. Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERα was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA–mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression. Results: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ERα. VAV3 was selectively reduced upon exposure to YC-1 or ERα depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 × 10−4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy. Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
Aguilar H, Urruticoechea A, Halonen P, Kiyotani K, Mushiroda T, Barril X, Serra-Musach J, Islam A, Caizzi L, Di Croce L et al. VAV3 mediates resistance to breast cancer endocrine therapy. Breast Cancer Research. 2014; 16: R53. DOI 10.1186/bcr3664
1465-5411
http://hdl.handle.net/10230/23244
http://dx.doi.org/10.1186/bcr3664
VAV3 mediates resistance to breast cancer endocrine therapy
oai:repositori.upf.edu:10230/232452018-01-24T08:31:16Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Almouzni, Geneviève
author
Estivill, Xavier, 1955-
author
Ossowski, Stephan
author
Widschwendter, Martin
author
2014
Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.
Almouzni G, Altucci L, Amati B, Ashley N, Baulcombe D, Beaujean N et al. Relationship between genome and epigenome - challenges and requirements for future research. BMC Genomics. 2014; 15: 487. DOI 10.1186/1471-2164-15-487
1471-2164
http://hdl.handle.net/10230/23245
http://dx.doi.org/10.1186/1471-2164-15-487
Relationship between genome and epigenome - challenges and requirements for future research
oai:repositori.upf.edu:10230/232522021-05-06T11:06:30Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Cutando Ruiz, Laura, 1985-
author
Busquets Garcia, Arnau, 1985-
author
Puighermanal Puigvert, Emma, 1983-
author
Gomis González, Maria, 1988-
author
Delgado García, José María
author
Gruart, Agnès
author
Maldonado, Rafael, 1961-
author
Ozaita Mintegui, Andrés, 1969-
author
2013
Chronic cannabis exposure can lead to cerebellar dysfunction in humans, but the neurobiological mechanisms involved remain incompletely understood. Here, we found that in mice, subchronic administration of the psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), activated cerebellar microglia and increased the expression of neuroinflammatory markers, including IL-1β. This neuroinflammatory phenotype correlated with deficits in cerebellar conditioned learning and fine motor coordination. The neuroinflammatory phenotype was readily detectable in the cerebellum of mice with global loss of the CB1 cannabinoid receptor (CB1R, Cb1(-/-) mice) and in mice lacking CB1R in the cerebellar parallel fibers, suggesting that CB1R downregulation in the cerebellar molecular layer plays a key role in THC-induced cerebellar deficits. Expression of CB2 cannabinoid receptor (CB2R) and Il1b mRNA was increased under neuroinflammatory conditions in activated CD11b-positive microglial cells. Furthermore, administration of the immunosuppressant minocycline or an inhibitor of IL-1β receptor signaling prevented the deficits in cerebellar function in Cb1(-/-) and THC-withdrawn mice. Our results suggest that cerebellar microglial activation plays a crucial role in the cerebellar deficits induced by repeated cannabis exposure.
Cutando L, Busquets-Garcia A, Puighermanal E, Gomis-González M, Delgado-García JM, Gruart A et al. Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure. J Clin Invest. 2013;123(7):2816-31. DOI: 10.1172/JCI67569
0021-9738
http://hdl.handle.net/10230/23252
http://dx.doi.org/10.1172/JCI67569
Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure
oai:repositori.upf.edu:10230/232552020-06-17T09:26:42Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Mellström, Britt
author
Sahún, Ignasi
author
Ruiz Nuño, Ana
author
Murtra, Patricia
author
Gómez Villafuertes, Rosa
author
Savignac, Magalí
author
Oliveros, Juan C.
author
González, Paz
author
Kastanauskaite, Asta
author
Knafo, Shira
author
Zhuo, Min
author
Higuera Matas, Alejandro
author
Errington, Michael L.
author
Maldonado, Rafael, 1961-
author
De Felipe, Javier
author
Jefferys, John G.R.
author
Bliss, Tim V. P.
author
Dierssen, Mara
author
Naranjo, José R.
author
2014
Changes in nuclear Ca(2+) homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K(+) channel interacting protein 3), is a Ca(2+)-binding protein that binds DNA and represses transcription in a Ca(2+)-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca(2+)-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory.
Mellström B, Sahún I, Ruiz-Nuño A, Murtra P, Gomez-Villafuertes R, Savignac M et al. DREAM controls the on/off switch of specific activity-dependent transcription pathways. Mol Cell Biol. 2014 Mar;34(5):877-87. DOI: 10.1128/MCB.00360-13
0270-7306
http://hdl.handle.net/10230/23255
http://dx.doi.org/10.1128/MCB.00360-13
DREAM controls the on/off switch of specific activity-dependent transcription pathways
oai:repositori.upf.edu:10230/232582018-07-12T17:04:49Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Cowled, Christopher
author
Stewart, Cameron R
author
Likic, Vladimir A
author
Friedländer, Marc R.
author
Tachedjian, Mary
author
Jenkins, Kristie A
author
Tizard, Mark L
author
Cottee, Pauline
author
Marsh, Glenn A
author
Zhou, Peng
author
Baker, Michelle L
author
Bean, Andrew G
author
Wang, Lin-fa
author
2014
Background: Bats are a major source of new and emerging viral diseases. Despite the fact that bats carry and shed highly pathogenic viruses including Ebola, Nipah and SARS, they rarely display clinical symptoms of infection. Host factors influencing viral replication are poorly understood in bats and are likely to include both pre- and post-transcriptional regulatory mechanisms. MicroRNAs are a major mechanism of post-transcriptional gene regulation, however very little is known about them in bats. Results: This study describes 399 microRNAs identified by deep sequencing of small RNA isolated from tissues of the Black flying fox, Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra virus and Australian bat lyssavirus. Of the microRNAs identified, more than 100 are unique amongst vertebrates, including a subset containing mutations in critical seed regions. Clusters of rapidly-evolving microRNAs were identified, as well as microRNAs predicted to target genes involved in antiviral immunity, the DNA damage response, apoptosis and autophagy. Closer inspection of the predicted targets for several highly supported novel miRNA candidates suggests putative roles in host-virus interaction. Conclusions: MicroRNAs are likely to play major roles in regulating virus-host interaction in bats, via dampening of inflammatory responses (limiting the effects of immunopathology), and directly limiting the extent of viral replication, either through restricting the availability of essential factors or by controlling apoptosis. Characterisation of the bat microRNA repertoire is an essential step towards understanding transcriptional regulation during viral infection, and will assist in the identification of mechanisms that enable bats to act as natural virus reservoirs. This in turn will facilitate the development of antiviral strategies for use in humans and other species.
Cowled C, Stewart CR, Likic VA, Friedländer MR, Tachedjian M, Jenkins KA, Tizard ML, Cottee P, Marsh GA, Zhou P, Baker ML, Bean AG, Wang LF. Characterisation of novel microRNAs in the Black flying fox (Pteropus alecto) by deep sequencing. BMC Genomics. 2014; 15: 682. DOI 10.1186/1471-2164-15-682
1471-2164
http://hdl.handle.net/10230/23258
http://dx.doi.org/10.1186/1471-2164-15-682
Characterisation of novel microRNAs in the Black flying fox (Pteropus alecto) by deep sequencing
oai:repositori.upf.edu:10230/232732019-04-10T13:30:15Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Cantó, Ester
author
Tintoré, Mar
author
Villar, Luisa Maria
author
Borrás, Eva
author
Álvarez Cermeño, Jose Carlos
author
Chiva, Cristina
author
Sabidó Aguadé, Eduard, 1981-
author
Rovira, Alex
author
Montalbán Gairín, Xavier
author
Comabella López, Manuel
author
2014
Background: In a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-?-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques. Methods: In a first replication study, levels of apolipoproteins AI and AIV, vitronectin, and plasminogen were measured by ELISA in CSF and serum of 56 CIS patients (29 patients who converted to CDMS (MS converters) and 27 patients who remained with CIS during follow-up (MS non-converters)) and 26 controls with other neurological disorders. Semaphorin 7A and ala-?-his-dipeptidase levels were determined by selected reaction monitoring (SRM) in CSF of 36 patients (18 MS converters, 18 non-converters) and 20 controls. In a second replication study, apolipoprotein AI levels were measured by ELISA in CSF of 74 CIS patients (47 MS converters, 27 non-converters) and 50 individual controls, and levels of semaphorin 7A and ala-beta-his-dipeptidase were determined by SRM in 49 patients (24 MS converters, 25 non-converters) and 22 controls. Results: CSF levels of apolipoprotein AI were increased (P = 0.043) and levels of semaphorin 7A and ala-?-his-dipeptidase decreased (P = 4.4?×?10?10 and P = 0.033 respectively) in MS converters compared to non-converters. No significant differences were found in serum levels for apolipoproteins AI and AIV, vitronectin, and plasminogen. Findings with semaphorin 7A and ala-?-his-dipeptidase were also validated in the second replication study, and CSF levels for these two proteins were again decreased in MS converters versus non-converters (P = 1.2?×?10?4 for semaphorin 7A; P = 3.7?×?10?8 for ala-?-his-dipeptidase). Conversely, apolipoprotein AI findings were not replicated and CSF levels for this protein did not significantly differ between groups. Furthermore, CSF semaphorin 7A levels were negatively associated with the number of T2 lesions at baseline and one-year follow-up. Conclusions: These results validate previous findings for semaphorin 7A and ala-?-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients.
Cantó E, Tintoré M, Villar LM, Borrás E, Alvarez-Cermeño JC, Chiva C, Sabidó E, Rovira A, Montalban X, Comabella M. Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis. Journal of Neuroinflammation. 2014; 11: 181. DOI 10.1186/s12974-014-0181-8
1742-2094
http://hdl.handle.net/10230/23273
http://dx.doi.org/10.1186/s12974-014-0181-8
Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis
oai:repositori.upf.edu:10230/232742018-01-24T08:09:12Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Castanera, Raúl
author
Pérez, Gúmer
author
López, Leticia
author
Sancho, Rubén
author
Santoyo, Francisco
author
Alfaro, Manuel
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Pisabarro, Antonio G
author
Oguiza, José A
author
Ramírez, Lucía
author
2014
Background: Helitrons are class-II eukaryotic transposons that transpose via a rolling circle mechanism. Due to their ability to capture and mobilize gene fragments, they play an important role in the evolution of their host genomes. We have used a bioinformatics approach for the identification of helitrons in two Pleurotus ostreatus genomes using de novo detection and homology-based searching. We have analyzed the presence of helitron-captured genes as well as the expansion of helitron-specific helicases in fungi and performed a phylogenetic analysis of their conserved domains with other representative eukaryotic species. Results: Our results show the presence of two helitron families in P. ostreatus that disrupt gene colinearity and cause a lack of synteny between their genomes. Both putative autonomous and non-autonomous helitrons were transcriptionally active, and some of them carried highly expressed captured genes of unknown origin and function. In addition, both families contained eukaryotic, bacterial and viral domains within the helitron’s boundaries. A phylogenetic reconstruction of RepHel helicases using the Helitron-like and PIF1-like helicase conserved domains revealed a polyphyletic origin for eukaryotic helitrons. Conclusion: P. ostreatus helitrons display features similar to other eukaryotic helitrons and do not tend to capture host genes or gene fragments. The occurrence of genes probably captured from other hosts inside the helitrons boundaries pose the hypothesis that an ancient horizontal transfer mechanism could have taken place. The viral domains found in some of these genes and the polyphyletic origin of RepHel helicases in the eukaryotic kingdom suggests that virus could have played a role in a putative lateral transfer of helitrons within the eukaryotic kingdom. The high similarity of some helitrons, along with the transcriptional activity of its RepHel helicases indicates that these elements are still active in the genome of P. ostreatus.
Castanera R, Pérez G, López L, Sancho R, Santoyo F, Alfaro M et al. Highly expressed captured genes and cross-kingdom domains present in Helitrons create novel diversity in Pleurotus ostreatus and other fungi. BMC Genomics. 2014; 15: 1071. DOI 10.1186/1471-2164-15-1071
1471-2164
http://hdl.handle.net/10230/23274
http://dx.doi.org/10.1186/1471-2164-15-1071
Highly expressed captured genes and cross-kingdom domains present in Helitrons create novel diversity in Pleurotus ostreatus and other fungi
oai:repositori.upf.edu:10230/232812020-02-28T09:37:03Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Molas Casacuberta, Susanna, 1985-
author
Gener, Thomas
author
Güell, Jofre
author
Martín, Mairena
author
Ballesteros Yáñez, Inmaculada
author
Sanchez-Vives, Maria V.
author
Dierssen, Mara
author
2014
Addiction involves long-lasting maladaptive changes including development of disruptive drug-stimuli associations. Nicotine-induced neuroplasticity underlies the development of tobacco addiction but also, in regions such as the hippocampus, the ability of this drug to enhance cognitive capabilities. Here, we propose that the genetic locus of susceptibility to nicotine addiction, the CHRNA5/A3/B4 gene cluster, encoding the ?5, ?3 and ?4 subunits of the nicotinic acetylcholine receptors (nAChRs), may influence nicotine-induced neuroadaptations. We have used transgenic mice overexpressing the human cluster (TgCHRNA5/A3/B4) to investigate hippocampal structure and function in genetically susceptible individuals. TgCHRNA5/A3/B4 mice presented a marked reduction in the dendrite complexity of CA1 hippocampal pyramidal neurons along with an increased dendritic spine density. In addition, TgCHRNA5/A3/B4 exhibited increased VGLUT1/VGAT ratio in the CA1 region, suggesting an excitatory/inhibitory imbalance. These hippocampal alterations were accompanied by a significant impairment in short-term novelty recognition memory. Interestingly, chronic infusion of nicotine (3.25 mg/kg/d for 7 d) was able to rescue the reduced dendritic complexity, the excitatory/inhibitory imbalance and the cognitive impairment in TgCHRNA5/A3/B4. Our results suggest that chronic nicotine treatment may represent a compensatory strategy in individuals with altered expression of the CHRNA5/A3/B4 region.
Molas S, Gener T, Güell J, Martín M, Ballesteros-Yáñez I, Sanchez-Vives MV, Dierssen M. Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice. Acta Neuropathologica Communications. 2014; 2(1): 147. DOI 10.1186/s40478-014-0147-1
2051-5960
http://hdl.handle.net/10230/23281
http://dx.doi.org/10.1186/s40478-014-0147-1
Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice
oai:repositori.upf.edu:10230/232852024-01-22T14:11:23Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Llorens, Franc
author
Hummel, Manuela
author
Pastor Ruiz, Javier
author
Ferrer Salvador, Anna
author
Pluvinet, Raquel
author
Vivancos Prellezo, Ana
author
Castillo Andreo, Esther
author
Iraola Guzmán, Susana
author
Mosquera Miguel, Ana
author
González-Roca, Eva
author
Lozano, Juan José
author
Ingham, Matthew
author
Dohm, Juliane C.
author
Noguera, Marc
author
Kofler, Robert
author
Río, Jose Antonio del
author
Bayés, Mònica
author
Himmelbauer, Heinz
author
Sumoy Van Dyck, Lauro
author
2011
Background: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. Results: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. Conclusions: We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.
Llorens F, Hummel M, Pastor X, Ferrer A, Pluvinet R, Vivancos A, Castillo E, Iraola S, Mosquera AM, González E, Lozano J, Ingham M, Dohm JC, Noguera M, Kofler R, del Río J, Bayés M, Himmelbauer H, Sumoy L. Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis. BMC Genomics. 2011; 12: 326. DOI 10.1186/1471-2164-12-326
1471-2164
http://hdl.handle.net/10230/23285
http://dx.doi.org/10.1186/1471-2164-12-326
Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis
oai:repositori.upf.edu:10230/233072021-05-06T11:06:56Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Busquets Garcia, Arnau, 1985-
author
Gomis González, Maria, 1988-
author
Guegan, Thomas, 1983-
author
Agustín Pavón, Carmen
author
Pastor, Antonio
author
Mato, Susana
author
Pérez Samartín, A.
author
Matute, Carlos
author
Torre Fornell, Rafael de la
author
Dierssen, Mara
author
Maldonado, Rafael, 1961-
author
Ozaita Mintegui, Andrés, 1969-
author
2013
Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation. The Fmr1 knockout model recapitulates the main traits of the disease. Uncontrolled activity of metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) signaling seem crucial in the pathology of this disease. The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice. We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.
Busquets-Garcia A, Gomis-González M, Guegan T, Agustín-Pavón C, Pastor A, Mato S et al. Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat Med. 2013 May;19(5):603-7. DOI: 10.1038/nm.3127
1078-8956
http://hdl.handle.net/10230/23307
http://dx.doi.org/10.1038/nm.3127
Targeting the endocannabinoid system in the treatment of fragile X syndrome
oai:repositori.upf.edu:10230/233222018-01-24T08:08:09Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Negre de Bofarull, Bárbara
author
Simpson, Pat
author
2013
Background: Transposable elements (TEs) are a very dynamic component of eukaryotic genomes with important implications (e.g., in evolution) and applications (e.g., as transgenic tools). They also represent a major challenge for the assembly and annotation of genomic sequences. However, they are still largely unknown in non-model species. Results: Here, we have annotated the repeats and transposable elements present in a 600 kb genomic region of the blowfly Calliphora vicina (Diptera: Calliphoridae) which contains most of the achaete-scute gene complex of this species. This is the largest genomic region to be sequenced and analyzed in higher flies outside the Drosophila genus. We find that the repeat content spans at least 24% of the sequence. It includes 318 insertions classified as 3 LTR retrotransposons, 21 LINEs, 14 cut-and-paste DNA transposons, 4 helitrons and 33 unclassified repeats. Conclusions: This is the most detailed description of TEs and repeats in the Calliphoridae to date. This contribution not only adds to our knowledge about TE evolution but will also help in the annotation of repeats on Dipteran whole genome sequences.
Negre B, Simpson P. Diversity of transposable elements and repeats in a 600 kb region of the fly Calliphora vicina. Mobille DNA. 2013; 4: 13. DOI 10.1186/1759-8753-4-13
1759-8753
http://hdl.handle.net/10230/23322
http://dx.doi.org/10.1186/1759-8753-4-13
Diversity of transposable elements and repeats in a 600 kb region of the fly Calliphora vicina
oai:repositori.upf.edu:10230/233232018-01-24T08:08:33Zcom_10230_20545com_10230_5542col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Vavouri, Tanya
author
Lehner, Ben, 1978-
author
2012
Background: More than 50% of human genes initiate transcription from CpG dinucleotide-rich regions referred to as CpG islands. These genes show differences in their patterns of transcription initiation, and have been reported to have higher levels of some activation-associated chromatin modifications. Results: Here we report that genes with CpG island promoters have a characteristic transcription-associated chromatin organization. This signature includes high levels of the transcription elongation-associated histone modifications H4K20me1, H2BK5me1 and H3K79me1/2/3 in the 5' end of the gene, depletion of the activation marks H2AK5ac, H3K14ac and H3K23ac immediately downstream of the transcription start site (TSS), and characteristic epigenetic asymmetries around the TSS. The chromosome organization factor CTCF may be bound upstream of RNA polymerase in most active CpG island promoters, and an unstable nucleosome at the TSS may be specifically marked by H4K20me3, the first example of such a modification. H3K36 monomethylation is only detected as enriched in the bodies of active genes that have CpG island promoters. Finally, as expression levels increase, peak modification levels of the histone methylations H3K9me1, H3K4me1, H3K4me2 and H3K27me1 shift further away from the TSS into the gene body. Conclusions: These results suggest that active genes with CpG island promoters have a distinct step-like series of modified nucleosomes after the TSS. The identity, positioning, shape and relative ordering of transcription-associated histone modifications differ between genes with and without CpG island promoters. This supports a model where chromatin organization reflects not only transcription activity but also the type of promoter in which transcription initiates.
Vavouri T, Lehner B. Human genes with CpG island promoters have a distinct transcription-associated chromatin organization. Genome Biology. 2012; 13(11): R110. DOI 10.1186/gb-2012-13-11-r110
1465-6906
http://hdl.handle.net/10230/23323
http://dx.doi.org/10.1186/gb-2012-13-11-r110
Human genes with CpG island promoters have a distinct transcription-associated chromatin organization
oai:repositori.upf.edu:10230/233242018-01-24T08:08:49Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Amid, Clara
author
Frankish, Adam
author
HAVANA
author
Aken, Bronwen
author
Ezkurdia, Iakes
author
Kokocinski, Felix
author
Gilbert, James
author
White, Simon
author
Carninci, Piero
author
Gingeras, Thomas R.
author
Guigó Serra, Roderic
author
Searle, Stephen
author
Tress, Michael
author
Harrow, Jennifer
author
Hubbard, Tim J.
author
2010
Amid C, Frankish A, Aken B, Ezkurdia T, Kokocinsk F, Gilbert J, White S, Carninci P, Gingeras T, Guigo R, Searle S, Tress ML, Harrow J, Hubbard T. From identification to validation to gene count. Genome Biology. 2010; 11(Suppl 1): O1. DOI 10.1186/gb-2010-11-s1-o1
1465-6906
http://hdl.handle.net/10230/23324
http://dx.doi.org/10.1186/gb-2010-11-s1-o1
From identification to validation to gene count
oai:repositori.upf.edu:10230/233412020-06-17T10:36:56Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227col_10230_8581
00925njm 22002777a 4500
dc
Erb, Ionas
author
González-Vallinas Rostes, Juan, 1983-
author
Bussotti, Giovanni, 1983-
author
Blanco, Enrique
author
Eyras Jiménez, Eduardo
author
Notredame, Cedric
author
2012
We address the challenge of regulatory sequence alignment with a new method, Pro-Coffee, a multiple aligner specifically designed for homologous promoter regions. Pro-Coffee uses a dinucleotide substitution matrix estimated on alignments of functional binding sites from TRANSFAC. We designed a validation framework using several thousand families of orthologous promoters. This dataset was used to evaluate the accuracy for predicting true human orthologs among their paralogs. We found that whereas other methods achieve on average 73.5% accuracy, and 77.6% when trained on that same dataset, the figure goes up to 80.4% for Pro-Coffee. We then applied a novel validation procedure based on multi-species ChIP-seq data. Trained and untrained methods were tested for their capacity to correctly align experimentally detected binding sites. Whereas the average number of correctly aligned sites for two transcription factors is 284 for default methods and 316 for trained methods, Pro-Coffee achieves 331, 16.5% above the default average. We find a high correlation between a method's performance when classifying orthologs and its ability to correctly align proven binding sites. Not only has this interesting biological consequences, it also allows us to conclude that any method that is trained on the ortholog data set will result in functionally more informative alignments.
Erb I, Gonzalez-Vallinas JR, Bussotti G, Blanco E, Eyras E, Notredame C. Use of ChIP-Seq data for the design of a multiple promoter-alignment method. Nucleic Acids Research. 2012; 40(7): e52. DOI 10.1093/nar/gkr1292
0305-1048
http://hdl.handle.net/10230/23341
http://dx.doi.org/10.1093/nar/gkr1292
Use of ChIP-Seq data for the design of a multiple promoter-alignment method
oai:repositori.upf.edu:10230/233502021-04-07T08:15:17Zcom_10230_6237com_10230_5542com_10230_20545com_10230_23115col_10230_6238col_10230_22227col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Viñals Álvarez, Xavier, 1985-
author
Molas Casacuberta, Susanna, 1985-
author
Gallego, Xavier
author
Fernández Montes, Rubén D.
author
Robledo, Patricia, 1958-
author
Dierssen, Mara
author
Maldonado, Rafael, 1961-
author
2012
Recent studies have revealed that sequence variants in genes encoding the α3/α5/β4 nicotinic acetylcholine receptor subunits are associated with nicotine dependence. In this study, we evaluated two specific aspects of executive functioning related to drug addiction (impulsivity and working memory) in transgenic mice over expressing α3/α5/β4 nicotinic receptor subunits. Impulsivity and working memory were evaluated in an operant delayed alternation task, where mice must inhibit responding between 2 and 8s in order to receive food reinforcement. Working memory was also evaluated in a spontaneous alternation task in an open field. Transgenic mice showed less impulsive-like behavior than wild-type controls, and this behavioral phenotype was related to the number of copies of the transgene. Thus, transgenic Line 22 (16-28 copies) showed a more pronounced phenotype than Line 30 (4-5 copies). Overexpression of these subunits in Line 22 reduced spontaneous alternation behavior suggesting deficits in working memory processing in this particular paradigm. These results reveal the involvement of α3/α5/β4 nicotinic receptor subunits in working memory and impulsivity, two behavioral traits directly related to the vulnerability to develop nicotine dependence.
Viñals X, Molas S, Gallego X, Fernández-Montes RD, Robledo P, Dierssen M et al. Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior. Drug Alcohol Depend. 2012 May 1;122(3):247-52. DOI: 10.1016/j.drugalcdep.2011.09.027
0376-8716
http://hdl.handle.net/10230/23350
http://dx.doi.org/10.1016/j.drugalcdep.2011.09.027
Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior
oai:repositori.upf.edu:10230/233512020-06-17T10:47:52Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
García, Patrícia
author
Paulo Mirasol, Esther, 1984-
author
Gao, Jun
author
Wahls, Wayne P
author
Ayté del Olmo, José
author
Lowy Gallego, Ernesto
author
Hidalgo Hernando, Elena
author
2014
Schizosaccharomyces pombe displays a large transcriptional response common to several stress conditions, regulated primarily by the transcription factor Atf1. Atf1-dependent promoters contain especially broad nucleosome depleted regions (NDRs) prior to stress imposition. We show here that basal binding of Atf1 to these promoters competes with histones to create wider NDRs at stress genes. Moreover, deletion of atf1 results in nucleosome disorganization specifically at stress coding regions and derepresses antisense transcription. Our data indicate that the transcription factor binding to promoters acts as an effective barrier to fix the +1 nucleosome and phase downstream nucleosome arrays to prevent cryptic transcription.
Garcia P, Paulo E, Gao J, Wahls WP, Ayté J, Lowy E, Hidalgo E. Binding of the transcription factor Atf1 to promoters serves as a barrier to phase nucleosome arrays and avoid cryptic transcription. Nucleic Acids Research. 2014; 42(16): 10351-10359. DOI 10.1093/nar/gku704
0305-1048
http://hdl.handle.net/10230/23351
http://dx.doi.org/10.1093/nar/gku704
Binding of the transcription factor Atf1 to promoters serves as a barrier to phase nucleosome arrays and avoid cryptic transcription
oai:repositori.upf.edu:10230/233942020-11-19T12:18:03Zcom_10230_6237com_10230_5542com_10230_20719com_10230_20545com_10230_23115col_10230_6238col_10230_22498col_10230_22227col_10230_23132col_10230_8581
00925njm 22002777a 4500
dc
Vrijheid, Martine
author
Robinson, Oliver
author
Basagaña Flores, Xavier
author
Bustamante Pineda, Mariona
author
Casas Sanahuja, Maribel
author
Estivill, Xavier, 1955-
author
van Gent, Diana
author
González Ruiz, Juan Ramón
author
Júlvez Calvo, Jordi
author
Kogevinas, Manolis
author
Sabidó Aguadé, Eduard, 1981-
author
Sunyer Deu, Jordi
author
Nieuwenhuijsen, Mark J.
author
2014
Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.
Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P et al. The human early-life exposome (HELIX): project rationale and design. Environ Health Perspect. 2014;122(6):535-44. DOI: 10.1289/ehp.1307204
0091-6765
http://hdl.handle.net/10230/23394
http://dx.doi.org/10.1289/ehp.1307204
The Human Early-Life Exposome (HELIX): project rationale and design
oai:repositori.upf.edu:10230/233952020-06-18T07:45:56Zcom_10230_6237com_10230_5542com_10230_20545com_10230_23115col_10230_6238col_10230_22227col_10230_23132
00925njm 22002777a 4500
dc
Santpere Baró, Gabriel, 1981-
author
Darre, Fleur
author
Blanco, Soledad
author
Alcami, Antonio
author
Villoslada, Pablo
author
Albà Soler, Mar
author
Navarro i Cuartiellas, Arcadi, 1969-
author
2014
Most people in the world (∼90%) are infected by the Epstein–Barr virus (EBV), which establishes itself permanently in B cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis, and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases. To perform a detailed comparative genomic analysis of EBV including, for the first time, EBV strains derived from healthy individuals, we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. As strain B95-8 was used to transform B cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605), we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis. We found that latency genes harbor more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging, and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host–parasite coevolution.
Santpere G, Darre F, Blanco S, Alcami A, Villoslada P, Alba MM, Navarro A. Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project. Genome Biol Evol. 2014;6(4):846-60. DOI: 10.1093/gbe/evu054
1759-6653
http://hdl.handle.net/10230/23395
http://dx.doi.org/10.1093/gbe/evu054
Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project
oai:repositori.upf.edu:10230/234102018-01-24T08:31:19Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Guigó Serra, Roderic
author
Richards, Stephan
author
Hunter, Wayne
author
Cámara, Francisco
author
2010
Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
Richards S, Gibbs RA, Gerardo NM, Moran N, Nakabachi A, Stern D et al. Genome sequence of the pea aphid Acyrthosiphon pisum. PLoS Biology. 2010; 8(2): e1000313. DOI 10.1371/journal.pbio.1000313
1544-9173
http://hdl.handle.net/10230/23410
http://dx.doi.org/10.1371/journal.pbio.1000313
Genome sequence of the pea aphid Acyrthosiphon pisum
oai:repositori.upf.edu:10230/234112018-01-24T08:07:15Zcom_10230_20545com_10230_5542col_10230_22227
00925njm 22002777a 4500
dc
Maxwell, Christopher A.
author
Guigó Serra, Roderic
author
Curado, Joao
author
Tilgner, Hagen, 1980-
author
Pujana, Miguel Angel
author
2011
Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02–1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94–1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
Maxwell CA, Benitez J, Gomez-Baldo L, Osorio A, Bonifaci N, Fernandez-Ramires R et al. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast. PLoS Biology. 2011; 9(11): e1001199. DOI 10.1371/journal.pbio.1001199
1544-9173
http://hdl.handle.net/10230/23411
http://dx.doi.org/10.1371/journal.pbio.1001199
Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast
oai:repositori.upf.edu:10230/234122020-06-18T08:18:17Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Chipman, Ariel D
author
Capella Gutiérrez, Salvador Jesús, 1985-
author
Gabaldón Estevan, Juan Antonio, 1973-
author
Guigó Serra, Roderic
author
Mariotti, Marco, 1984-
author
Richards, Stephan
author
2014
Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.
Chipman AD, Ferrier DEK, Brena C, Qu J, Hughes DST, Schroder R et al. The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede strigamia maritima. PLoS Biology. 2014;12(11):e1002005. DOI: 10.1371/journal.pbio.1002005
1544-9173
http://hdl.handle.net/10230/23412
http://dx.doi.org/10.1371/journal.pbio.1002005
The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede strigamia maritima
oai:repositori.upf.edu:10230/234192018-01-24T08:09:09Zcom_10230_6237com_10230_5542com_10230_20545col_10230_6238col_10230_22227
00925njm 22002777a 4500
dc
Guigó Serra, Roderic
author
Myers, Richard M.
author
Good, Peter J
author
2011
The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.
Meyer LR, Sloan CA, Malladi VS, Cline MS, Learned K, Swing VK et al. A user's guide to the Encyclopedia of DNA elements (ENCODE). PLoS Biology. 2011; 9(4): e1001046. DOI 10.1371/journal.pbio.1001046
1544-9173
http://hdl.handle.net/10230/23419
http://dx.doi.org/10.1371/journal.pbio.1001046
A user's guide to the Encyclopedia of DNA elements (ENCODE)
oai:repositori.upf.edu:10230/234412020-06-04T10:13:39Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238col_10230_8581
00925njm 22002777a 4500
dc
Barneda Zahonero, Bruna
author
Román González, Lidia
author
Collazo, Olga
author
Rafati, Haleh
author
Islam, Abul, 1978-
author
Bussmann, Lars
author
Di Tullio, Alessandro, 1982-
author
Andrés, Luisa De
author
Graf, T. (Thomas)
author
López Bigas, Núria
author
Mahmoudi, Tokameh
author
Parra, Maribel
author
2013
B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell–specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes.
Barneda-Zahonero B, Roman-Gonzalez L, Collazo O, Rafati H, Islam ABMMK, Bussmann LH et al. HDAC7 is a repressor of myeloid genes whose downregulation is required for transdifferentiation of pre-B cells into macrophages. PLoS Genetics. 2013;9(5):e1003503. DOI: 10.1371/journal.pgen.1003503
1553-7390
http://hdl.handle.net/10230/23441
http://dx.doi.org/10.1371/journal.pgen.1003503
HDAC7 is a repressor of myeloid genes whose downregulation is required for transdifferentiation of pre-B cells into macrophages
oai:repositori.upf.edu:10230/234422020-06-04T10:42:16Zcom_10230_20545com_10230_5542com_10230_6237col_10230_22227col_10230_6238
00925njm 22002777a 4500
dc
Marigorta, Urko M.
author
Navarro i Cuartiellas, Arcadi, 1969-
author
2013
Genome-wide association studies (GWAS) have detected many disease associations. However, the reported variants tend to explain small fractions of risk, and there are doubts about issues such as the portability of findings over different ethnic groups or the relative roles of rare versus common variants in the genetic architecture of complex disease. Studying the degree of sharing of disease-associated variants across populations can help in solving these issues. We present a comprehensive survey of GWAS replicability across 28 diseases. Most loci and SNPs discovered in Europeans for these conditions have been extensively replicated using peoples of European and East Asian ancestry, while the replication with individuals of African ancestry is much less common. We found a strong and significant correlation of Odds Ratios across Europeans and East Asians, indicating that underlying causal variants are common and shared between the two ancestries. Moreover, SNPs that failed to replicate in East Asians map into genomic regions where Linkage Disequilibrium patterns differ significantly between populations. Finally, we observed that GWAS with larger sample sizes have detected variants with weaker effects rather than with lower frequencies. Our results indicate that most GWAS results are due to common variants. In addition, the sharing of disease alleles and the high correlation in their effect sizes suggest that most of the underlying causal variants are shared between Europeans and East Asians and that they tend to map close to the associated marker SNPs.
Marigorta UM, Navarro A. High trans-ethnic replicability of GWAS results implies common causal variants. PLoS Genetics. 2013;9(6):e1003566. DOI: 10.1371/journal.pgen.1003566
1553-7390
http://hdl.handle.net/10230/23442
http://dx.doi.org/10.1371/journal.pgen.1003566
High trans-ethnic replicability of GWAS results implies common causal variants
marc///col_10230_22227/100