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2012
Autores
Dunham, I; Kundaje, A; Aldred, SF; Collins, PJ; Davis, C; Doyle, F; Epstein, CB; Frietze, S; Harrow, J; Kaul, R; Khatun, J; Lajoie, BR; Landt, SG; Lee, BK; Pauli, F; Rosenbloom, KR; Sabo, P; Safi, A; Sanyal, A; Shoresh, N; Simon, JM; Song, L; Trinklein, ND; Altshuler, RC; Birney, E; Brown, JB; Cheng, C; Djebali, S; Dong, XJ; Dunham, I; Ernst, J; Furey, TS; Gerstein, M; Giardine, B; Greven, M; Hardison, RC; Harris, RS; Herrero, J; Hoffman, MM; Iyer, S; Kellis, M; Khatun, J; Kheradpour, P; Kundaje, A; Lassmann, T; Li, QH; Lin, X; Marinov, GK; Merkel, A; Mortazavi, A; Parker, SCJ; Reddy, TE; Rozowsky, J; Schlesinger, F; Thurman, RE; Wang, J; Ward, LD; Whitfield, TW; Wilder, SP; Wu, W; Xi, HLS; Yip, KY; Zhuang, JL; Bernstein, BE; Birney, E; Dunham, I; Green, ED; Gunter, C; Snyder, M; Pazin, MJ; Lowdon, RF; Dillon, LAL; Adams, LB; Kelly, CJ; Zhang, J; Wexler, JR; Green, ED; Good, PJ; Feingold, EA; Bernstein, BE; Birney, E; Crawford, GE; Dekker, J; Elnitski, L; Farnham, PJ; Gerstein, M; Giddings, MC; Gingeras, TR; Green, ED; Guigo, R; Hardison, RC; Hubbard, TJ; Kellis, M; Kent, WJ; Lieb, JD; Margulies, EH; Myers, RM; Snyder, M; Stamatoyannopoulos, JA; Tenenbaum, SA; Weng, ZP; White, KP; Wold, B; Khatun, J; Yu, Y; Wrobel, J; Risk, BA; Gunawardena, HP; Kuiper, HC; Maier, CW; Xie, L; Chen, X; Giddings, MC; Bernstein, BE; Epstein, CB; Shoresh, N; Ernst, J; Kheradpour, P; Mikkelsen, TS; Gillespie, S; Goren, A; Ram, O; Zhang, XL; Wang, L; Issner, R; Coyne, MJ; Durham, T; Ku, M; Truong, T; Ward, LD; Altshuler, RC; Eaton, ML; Kellis, M; Djebali, S; Davis, CA; Merkel, A; Dobin, A; Lassmann, T; Mortazavi, A; Tanzer, A; Lagarde, J; Lin, W; Schlesinger, F; Xue, CH; Marinov, GK; Khatun, J; Williams, BA; Zaleski, C; Rozowsky, J; Roeder, M; Kokocinski, F; Abdelhamid, RF; Alioto, T; Antoshechkin, I; Baer, MT; Batut, P; Bell, I; Bell, K; Chakrabortty, S; Chen, X; Chrast, J; Curado, J; Derrien, T; Drenkow, J; Dumais, E; Dumais, J; Duttagupta, R; Fastuca, M; Fejes Toth, K; Ferreira, P; Foissac, S; Fullwood, MJ; Gao, H; Gonzalez, D; Gordon, A; Gunawardena, HP; Howald, C; Jha, S; Johnson, R; Kapranov, P; King, B; Kingswood, C; Li, GL; Luo, OJ; Park, E; Preall, JB; Presaud, K; Ribeca, P; Risk, BA; Robyr, D; Ruan, XA; Sammeth, M; Sandhu, KS; Schaeffer, L; See, LH; Shahab, A; Skancke, J; Suzuki, AM; Takahashi, H; Tilgner, H; Trout, D; Walters, N; Wang, HE; Wrobel, J; Yu, YB; Hayashizaki, Y; Harrow, J; Gerstein, M; Hubbard, TJ; Reymond, A; Antonarakis, SE; Hannon, GJ; Giddings, MC; Ruan, YJ; Wold, B; Carninci, P; Guigo, R; Gingeras, TR; Rosenbloom, KR; Sloan, CA; Learned, K; Malladi, VS; Wong, MC; Barber, G; Cline, MS; Dreszer, TR; Heitner, SG; Karolchik, D; Kent, WJ; Kirkup, VM; Meyer, LR; Long, JC; Maddren, M; Raney, BJ; Furey, TS; Song, LY; Grasfeder, LL; Giresi, PG; Lee, BK; Battenhouse, A; Sheffield, NC; Simon, JM; Showers, KA; Safi, A; London, D; Bhinge, AA; Shestak, C; Schaner, MR; Kim, SK; Zhang, ZZZ; Mieczkowski, PA; Mieczkowska, JO; Liu, Z; McDaniell, RM; Ni, YY; Rashid, NU; Kim, MJ; Adar, S; Zhang, ZC; Wang, TY; Winter, D; Keefe, D; Birney, E; Iyer, VR; Lieb, JD; Crawford, GE; Li, GL; Sandhu, KS; Zheng, MZ; Wang, P; Luo, OJ; Shahab, A; Fullwood, MJ; Ruan, XA; Ruan, YJ; Myers, RM; Pauli, F; Williams, BA; Gertz, J; Marinov, GK; Reddy, TE; Vielmetter, J; Partridge, EC; Trout, D; Varley, KE; Gasper, C; Bansal, A; Pepke, S; Jain, P; Amrhein, H; Bowling, KM; Anaya, M; Cross, MK; King, B; Muratet, MA; Antoshechkin, I; Newberry, KM; Mccue, K; Nesmith, AS; Fisher Aylor, KI; Pusey, B; DeSalvo, G; Parker, SL; Balasubramanian, S; Davis, NS; Meadows, SK; Eggleston, T; Gunter, C; Newberry, JS; Levy, SE; Absher, DM; Mortazavi, A; Wong, WH; Wold, B; Blow, MJ; Visel, A; Pennachio, LA; Elnitski, L; Margulies, EH; Parker, SCJ; Petrykowska, HM; Abyzov, A; Aken, B; Barrell, D; Barson, G; Berry, A; Bignell, A; Boychenko, V; Bussotti, G; Chrast, J; Davidson, C; Derrien, T; Despacio Reyes, G; Diekhans, M; Ezkurdia, I; Frankish, A; Gilbert, J; Gonzalez, JM; Griffiths, E; Harte, R; Hendrix, DA; Howald, C; Hunt, T; Jungreis, I; Kay, M; Khurana, E; Kokocinski, F; Leng, J; Lin, MF; Loveland, J; Lu, Z; Manthravadi, D; Mariotti, M; Mudge, J; Mukherjee, G; Notredame, C; Pei, BK; Rodriguez, JM; Saunders, G; Sboner, A; Searle, S; Sisu, C; Snow, C; Steward, C; Tanzer, A; Tapanari, E; Tress, ML; van Baren, MJ; Walters, N; Washietl, S; Wilming, L; Zadissa, A; Zhang, ZD; Brent, M; Haussler, D; Kellis, M; Valencia, A; Gerstein, M; Reymond, A; Guigo, R; Harrow, J; Hubbard, TJ; Landt, SG; Frietze, S; Abyzov, A; Addleman, N; Alexander, RP; Auerbach, RK; Balasubramanian, S; Bettinger, K; Bhardwaj, N; Boyle, AP; Cao, AR; Cayting, P; Charos, A; Cheng, Y; Cheng, C; Eastman, C; Euskirchen, G; Fleming, JD; Grubert, F; Habegger, L; Hariharan, M; Harmanci, A; Iyengar, S; Jin, VX; Karczewski, KJ; Kasowski, M; Lacroute, P; Lam, H; Lamarre Vincent, N; Leng, J; Lian, J; Lindahl Allen, M; Min, RQ; Miotto, B; Monahan, H; Moqtaderi, Z; Mu, XMJ; O'Geen, H; Ouyang, ZQ; Patacsil, D; Pei, BK; Raha, D; Ramirez, L; Reed, B; Rozowsky, J; Sboner, A; Shi, MY; Sisu, C; Slifer, T; Witt, H; Wu, LF; Xu, XQ; Yan, KK; Yang, XQ; Yip, KY; Zhang, ZD; Struhl, K; Weissman, SM; Gerstein, M; Farnham, PJ; Snyder, M; Tenenbaum, SA; Penalva, LO; Doyle, F; Karmakar, S; Landt, SG; Bhanvadia, RR; Choudhury, A; Domanus, M; Ma, LJ; Moran, J; Patacsil, D; Slifer, T; Victorsen, A; Yang, XQ; Snyder, M; White, KP; Auer, T; Centanin, L; Eichenlaub, M; Gruhl, F; Heermann, S; Hoeckendorf, B; Inoue, D; Kellner, T; Kirchmaier, S; Mueller, C; Reinhardt, R; Schertel, L; Schneider, S; Sinn, R; Wittbrodt, B; Wittbrodt, J; Weng, ZP; Whitfield, TW; Wang, J; Collins, PJ; Aldred, SF; Trinklein, ND; Partridge, EC; Myers, RM; Dekker, J; Jain, G; Lajoie, BR; Sanyal, A; Balasundaram, G; Bates, DL; Byron, R; Canfield, TK; Diegel, MJ; Dunn, D; Ebersol, AK; Frum, T; Garg, K; Gist, E; Hansen, RS; Boatman, L; Haugen, E; Humbert, R; Jain, G; Johnson, AK; Johnson, EM; Kutyavin, TV; Lajoie, BR; Lee, K; Lotakis, D; Maurano, MT; Neph, SJ; Neri, FV; Nguyen, ED; Qu, HZ; Reynolds, AP; Roach, V; Rynes, E; Sabo, P; Sanchez, ME; Sandstrom, RS; Sanyal, A; Shafer, AO; Stergachis, AB; Thomas, S; Thurman, RE; Vernot, B; Vierstra, J; Vong, S; Wang, H; Weaver, MA; Yan, YQ; Zhang, MH; Akey, JM; Bender, M; Dorschner, MO; Groudine, M; MacCoss, MJ; Navas, P; Stamatoyannopoulos, G; Kaul, R; Dekker, J; Stamatoyannopoulos, JA; Dunham, I; Beal, K; Brazma, A; Flicek, P; Herrero, J; Johnson, N; Keefe, D; Lukk, M; Luscombe, NM; Sobral, D; Vaquerizas, JM; Wilder, SP; Batzoglou, S; Sidow, A; Hussami, N; Kyriazopoulou Panagiotopoulou, S; Libbrecht, MW; Schaub, MA; Kundaje, A; Hardison, RC; Miller, W; Giardine, B; Harris, RS; Wu, W; Bickel, PJ; Banfai, B; Boley, NP; Brown, JB; Huang, HY; Li, QH; Li, JJ; Noble, WS; Bilmes, JA; Buske, OJ; Hoffman, MM; Sahu, AD; Kharchenko, PV; Park, PJ; Baker, D; Taylor, J; Weng, ZP; Iyer, S; Dong, XJ; Greven, M; Lin, XY; Wang, J; Xi, HLS; Zhuang, JL; Gerstein, M; Alexander, RP; Balasubramanian, S; Cheng, C; Harmanci, A; Lochovsky, L; Min, R; Mu, XMJ; Rozowsky, J; Yan, KK; Yip, KY; Birney, E;
Publicação
NATURE
Abstract
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.
2010
Autores
Novoa, I; Gallego, J; Ferreira, PG; Mendez, R;
Publicação
NATURE CELL BIOLOGY
Abstract
Meiotic and early-embryonic cell divisions in vertebrates take place in the absence of transcription and rely on the translational regulation of stored maternal messenger RNAs. Most of these mRNAs are regulated by the cytoplasmic-polyadenylation-element-binding protein (CPEB), which mediates translational activation and repression through cytoplasmic changes in their poly(A) tail length. It was unknown whether translational regulation by cytoplasmic polyadenylation and CPEB can also regulate mRNAs at specific points of mitotic cell-cycle divisions. Here we show that CPEB-mediated post-transcriptional regulation by phase-specific changes in poly(A) tail length is required for cell proliferation and specifically for entry into M phase in mitotically dividing cells. This translational control is mediated by two members of the CPEB family of proteins, CPEB1 and CPEB4. We conclude that regulation of poly(A) tail length is not only required to compensate for the lack of transcription in specialized cell divisions but also acts as a general mechanism to control mitosis.
2012
Autores
Djebali, S; Davis, CA; Merkel, A; Dobin, A; Lassmann, T; Mortazavi, A; Tanzer, A; Lagarde, J; Lin, W; Schlesinger, F; Xue, CH; Marinov, GK; Khatun, J; Williams, BA; Zaleski, C; Rozowsky, J; Roeder, M; Kokocinski, F; Abdelhamid, RF; Alioto, T; Antoshechkin, I; Baer, MT; Bar, NS; Batut, P; Bell, K; Bell, I; Chakrabortty, S; Chen, X; Chrast, J; Curado, J; Derrien, T; Drenkow, J; Dumais, E; Dumais, J; Duttagupta, R; Falconnet, E; Fastuca, M; Fejes Toth, K; Ferreira, P; Foissac, S; Fullwood, MJ; Gao, H; Gonzalez, D; Gordon, A; Gunawardena, H; Howald, C; Jha, S; Johnson, R; Kapranov, P; King, B; Kingswood, C; Luo, OJ; Park, E; Persaud, K; Preall, JB; Ribeca, P; Risk, B; Robyr, D; Sammeth, M; Schaffer, L; See, LH; Shahab, A; Skancke, J; Suzuki, AM; Takahashi, H; Tilgner, H; Trout, D; Walters, N; Wang, H; Wrobel, J; Yu, YB; Ruan, XA; Hayashizaki, Y; Harrow, J; Gerstein, M; Hubbard, T; Reymond, A; Antonarakis, SE; Hannon, G; Giddings, MC; Ruan, YJ; Wold, B; Carninci, P; Guigo, R; Gingeras, TR;
Publicação
NATURE
Abstract
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.
2007
Autores
Librelotto, GR; Machado, HT; Martins, M; Ferreira, PGD; Ramalho, JC; Henriques, PR;
Publicação
Proceedings of Extreme Markup Languages 2007 Conference
Abstract
This paper presents a topic map approach to PubMed in order to create a knowledge representation for this information system. PubMed is a free search engine that gives very full coverage of the related biomedical sciences. With more than 17 millions of citations since 1865, PubMed users have several problems to find the papers desired. So, it is necessary to organize these concepts in a semantic network. To achieve this objective, we use the Metamorphosis system, choosing the keywords from MeSH ontology. This way, we obtain an ontological index for PubMed, making easier to find specific papers. Copyright © 2007 Giovani Rubert Librelotto, Henrique Tamiosso Machado, Mirkos Martins, Pedro Gabriel Dias Ferreira, José Carlos Ramalho, and Pedro Rangel Henriques.
2012
Autores
Plass, M; Codony Servat, C; Gabriel Ferreira, PG; Vilardell, J; Eyras, E;
Publicação
RNA-A PUBLICATION OF THE RNA SOCIETY
Abstract
Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3' splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3'ss in the CDS and 5' UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3'ss. Experimental validation of a number of predicted alternative 3'ss shows that their usage is low compared to annotated 3'ss. The majority of these alternative 3'ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3'ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.
2012
Autores
Alves, R; Ferreira, P; Ribeiro, J; Belo, O;
Publicação
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Abstract
Graphs are a very important abstraction to model complex structures and respective interactions, with a broad range of applications including web analysis, telecommunications, chemical informatics and bioinformatics. In this work we are interested in the application of graph mining to identify abnormal behavior patterns from telecom Call Detail Records (CDRs). Such behaviors could also be used to model essential business tasks in telecom, for example churning, fraud, or marketing strategies, where the number of customers is typically quite large. Therefore, it is important to rank the most interesting patterns for further analysis. We propose a vertex relevant ranking score as a unified measure for focusing the search of abnormal patterns in weighted call graphs based on CDRs. Classical graph-vertex measures usually expose a quantitative perspective of vertices in telecom call graphs. We aggregate wellknown vertex measures for handling attribute-based information usually provided by CDRs. Experimental evaluation carried out with real data streams, from a local mobile telecom company, showed us the feasibility of the proposed strategy. © 2012 Springer-Verlag.
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