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1. Expanded encyclopaedias of DNA elements in the human and mouse genomes

Author

Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, 1.1 Normal biological development and functioning, Animals, Chromatin, DNA, DNA Footprinting, DNA Methylation, DNA Replication Timing, Databases, Genetic, Deoxyribonuclease I, Genome, Genome, Human, Genomics, Histones, Humans, Mice, Mice, Transgenic, Molecular Sequence Annotation, RNA-Binding Proteins, Registries, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Transposases, ENCODE Project Consortium, General Science & Technology
Abstract

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

Published
2020

2. Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Author

ENCODE Project Consortium, Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping

Subjects
ENCODE Project Consortium, Chromatin, Animals, Mice, Transgenic, Humans, Mice, Deoxyribonuclease I, Transposases, RNA-Binding Proteins, Histones, DNA, Registries, DNA Footprinting, Genomics, DNA Methylation, DNA Replication Timing, Transcription, Genetic, Regulatory Sequences, Nucleic Acid, Genome, Genome, Human, Databases, Genetic, Molecular Sequence Annotation, Human Genome, HIV/AIDS, Vaccine Related, Biotechnology, Genetics, Immunization, Vaccine Related (AIDS), Prevention, 1.1 Normal biological development and functioning, Generic health relevance, General Science & Technology
Abstract

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

Published
2020

3. Genetic and epigenetic fine mapping of causal autoimmune disease variants

Author

Farh, Kyle Kai-How, Marson, Alexander, Zhu, Jiang, Kleinewietfeld, Markus, Housley, William J, Beik, Samantha, Shoresh, Noam, Whitton, Holly, Ryan, Russell JH, Shishkin, Alexander A, Hatan, Meital, Carrasco-Alfonso, Marlene J, Mayer, Dita, Luckey, C John, Patsopoulos, Nikolaos A, De Jager, Philip L, Kuchroo, Vijay K, Epstein, Charles B, Daly, Mark J, Hafler, David A, and Bernstein, Bradley E

Subjects
Immunization, Human Genome, Vaccine Related, Autoimmune Disease, Genetics, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Underpinning research, Inflammatory and immune system, Autoimmune Diseases, Base Sequence, Chromatin, Consensus Sequence, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Genome-Wide Association Study, Humans, Nucleotide Motifs, Organ Specificity, Polymorphism, Single Nucleotide, T-Lymphocytes, Transcription Factors, General Science & Technology
Abstract

Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4(+) T-cell subsets, regulatory T cells, CD8(+) T cells, B cells, and monocytes. We find that ∼90% of causal variants are non-coding, with ∼60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10-20% directly alter recognizable transcription factor binding motifs. Rather, most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.

Published
2015

4. Comparative analysis of metazoan chromatin organization

Author

Ho, Joshua WK, Jung, Youngsook L, Liu, Tao, Alver, Burak H, Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y, Appert, Alex, Parker, Stephen CJ, Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C, Bishop, Eric, Egelhofer, Thea A, Hu, Sheng'en Shawn, Alekseyenko, Artyom A, Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A, Bowman, Sarah K, Chen, Q Brent, Chen, Ron A-J, Day, Daniel S, Dong, Yan, Dose, Andrea C, Duan, Xikun, Epstein, Charles B, Ercan, Sevinc, Feingold, Elise A, Ferrari, Francesco, Garrigues, Jacob M, Gehlenborg, Nils, Good, Peter J, Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M, Jeffers, Tess E, Kharchenko, Peter V, Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V, Kumar, Nischay, Langley, Sasha A, Larschan, Erica N, Latorre, Isabel, Libbrecht, Maxwell W, Lin, Xueqiu, Park, Richard, Pazin, Michael J, Pham, Hoang N, Plachetka, Annette, Qin, Bo, Schwartz, Yuri B, Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M, Xue, Huiling, Kingston, Robert E, Kim, Ju Han, Bernstein, Bradley E, Dernburg, Abby F, Pirrotta, Vincenzo, Kuroda, Mitzi I, Noble, William S, Tullius, Thomas D, Kellis, Manolis, MacAlpine, David M, Strome, Susan, Elgin, Sarah CR, Liu, Xiaole Shirley, Lieb, Jason D, Ahringer, Julie, Karpen, Gary H, and Park, Peter J

Subjects
Biochemistry and Cell Biology, Biological Sciences, Immunization, Human Genome, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Caenorhabditis elegans, Cell Line, Centromere, Chromatin, Chromatin Assembly and Disassembly, DNA Replication, Drosophila melanogaster, Enhancer Elements, Genetic, Epigenesis, Genetic, Heterochromatin, Histones, Humans, Molecular Sequence Annotation, Nuclear Lamina, Nucleosomes, Promoter Regions, Genetic, Species Specificity, General Science & Technology
Abstract

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Published
2014

5. Mapping and analysis of chromatin state dynamics in nine human cell types

Author

Ernst, Jason, Kheradpour, Pouya, Mikkelsen, Tarjei S, Shoresh, Noam, Ward, Lucas D, Epstein, Charles B, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael, Ku, Manching, Durham, Timothy, Kellis, Manolis, and Bernstein, Bradley E

Subjects
Genetics, Biotechnology, Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Binding Sites, Cell Line, Cell Line, Tumor, Cell Physiological Phenomena, Cells, Cultured, Chromatin, Chromosome Mapping, Gene Expression Regulation, Genome, Human, Hep G2 Cells, Humans, Promoter Regions, Genetic, Reproducibility of Results, Transcription Factors, General Science & Technology
Abstract

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.

Published
2011

6. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types

Author

Finucane, Hilary K, Reshef, Yakir A, Anttila, Verneri, Slowikowski, Kamil, Gusev, Alexander, Byrnes, Andrea, Gazal, Steven, Loh, Po-Ru, Lareau, Caleb, Shoresh, Noam, Genovese, Giulio, Saunders, Arpiar, Macosko, Evan, Pollack, Samuela, Brainstorm Consortium, Perry, John RB, Buenrostro, Jason D, Bernstein, Bradley E, Raychaudhuri, Soumya, McCarroll, Steven, Neale, Benjamin M, and Price, Alkes L

Subjects
2. Zero hunger, Neurons, Multifactorial Inheritance, Bipolar Disorder, Models, Genetic, Gene Expression Profiling, Brain, Gene Expression, Chromatin, Linkage Disequilibrium, Body Mass Index, Epigenesis, Genetic, Immune System Diseases, Schizophrenia, Humans, Genetic Predisposition to Disease, Tissue Distribution, Genome-Wide Association Study
Abstract

We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We applied our approach to gene expression data from several sources together with GWAS summary statistics for 48 diseases and traits (average N = 169,331) and found significant tissue-specific enrichments (false discovery rate (FDR) < 5%) for 34 traits. In our analysis of multiple tissues, we detected a broad range of enrichments that recapitulated known biology. In our brain-specific analysis, significant enrichments included an enrichment of inhibitory over excitatory neurons for bipolar disorder, and excitatory over inhibitory neurons for schizophrenia and body mass index. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signals.

7. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

Author

Zhi Lu, Giltae Song, Troy W. Whitfield, Vishwanath R. Iyer, Teresa Vales, Angelika Merkel, Max Libbrecht, David Haussler, Ting Wang, Kristen Lee, Lingyun Song, Richard M. Myers, Alfonso Valencia, Rachel A. Harte, Xiaoqin Xu, Lucas D. Ward, Hazuki Takahashi, Nathan C. Sheffield, Thomas Derrien, Georgi K. Marinov, Eric D. Nguyen, Bernard B. Suh, Brian J. Raney, Richard Sandstrom, Thomas D. Tullius, Benoit Miotto, Alexander Dobin, Youhan Xu, Lukas Habegger, Ian Dunham, Brian A. Risk, Paul G. Giresi, Morgan C. Giddings, Hualin Xi, Anshul Kundaje, Robert S. Harris, Devin Absher, Peter J. Bickel, Yanbao Yu, Browen Aken, Colin Kingswood, Bryan R. Lajoie, Peter J. Good, Katrina Learned, Laura Elnitski, Shirley Pepke, Brandon King, Piero Carninci, Xinqiong Yang, Ghia Euskirchen, Kathryn Beal, Christelle Borel, Michael Muratet, Robert L. Grossman, David G. Knowles, Zarmik Moqtaderi, Veronika Boychenko, Steven P. Wilder, Michael L. Tress, Florencia Pauli, Alan P. Boyle, Andrea Tanzer, Philipp Kapranov, Serafim Batzoglou, Audra K. Johnson, Jun Neri, Nitin Bhardwaj, Elise A. Feingold, Venkat S. Malladi, Michael M. Hoffman, William Stafford Noble, Andrea Sboner, Mark Gerstein, Stephanie L. Parker, Jacqueline Dumais, Felix Schlesinger, Deborah R. Winter, Randall H. Brown, Thanh Truong, Rebecca F. Lowdon, Paolo Ribeca, Brooke Rhead, Peggy J. Farnham, Krista Thibeault, Terrence S. Furey, Donna Karolchik, Alec Victorsen, Xiaoan Ruan, Rehab F. Abdelhamid, Amy S. Nesmith, Jing Wang, Nicholas M. Luscombe, Alina R. Cao, Diane Trout, Teri Slifer, Peter E. Newburger, Cricket A. Sloan, Dimitra Lotakis, Stephen M. J. Searle, Ali Mortazavi, Alexandra Bignell, Alex Reynolds, Orion J. Buske, Chris Zaleski, Theresa K. Canfield, Ian Bell, Jin Lian, Vanessa K. Swing, Katalin Toth Fejes, Catherine Ucla, Robert E. Thurman, Jacqueline Chrast, Wei Lin, Tim Hubbard, Gary Saunders, Minyi Shi, Vihra Sotirova, Sherman M. Weissman, Jason D. Lieb, Richard Humbert, Kevin M. Bowling, Assaf Gordon, Tarjei S. Mikkelsen, Jing Leng, Thomas R. Gingeras, Fabian Grubert, Nader Jameel, Jost Vielmetter, Hannah Monahan, Preti Jain, Lindsay L. Waite, Tony Shafer, Joel Rozowsky, Michael Coyne, Brian Reed, M. Kay, Harsha P. Gunawardena, Ross C. Hardison, Gavin Sherlock, Alexandra Charos, Joseph D. Fleming, Ann S. Zweig, Jason Gertz, Rajinder Kaul, Xianjun Dong, Alexandre Reymond, Carrie A. Davis, Haiyan Huang, Chao Cheng, Marco Mariotti, Phil Lacroute, Jason A. Dilocker, Kenneth McCue, R. Robilotto, Stylianos E. Antonarakis, Sridar V. Chittur, Justin Jee, Barbara J. Wold, Sudipto K. Chakrabortty, Erica Dumais, Amartya Sanyal, Nathan Boley, Tianyuan Wang, Julien Lagarde, Anthony Kirilusha, Jonathan B. Preall, Kevin Roberts, Erika Giste, Hugo Y. K. Lam, Alvis Brazma, Gregory J. Hannon, Eric Rynes, Philippe Batut, Kevin Struhl, Margus Lukk, Manching Ku, Suganthi Balasubramanian, Sonali Jha, Jorg Drenkow, W. James Kent, Michael Snyder, Jie Wang, Anna Battenhouse, Charles B. Epstein, Rami Rauch, Christopher Shestak, John A. Stamatoyannopoulos, Gaurab Mukherjee, Cédric Howald, Tanya Kutyavin, Huaien Wang, Scott A. Tenenbaum, Wan Ting Poh, Kate R. Rosenbloom, Manolis Kellis, Pauline A. Fujita, Linfeng Wu, Anita Bansal, Molly Weaver, Linda L. Grasfeder, Peter J. Sabo, Qiang Li, Melissa S. Cline, Robert M. Kuhn, Darin London, Seth Frietze, Atif Shahab, Shane Neph, Damian Keefe, James B. Brown, Mark Diekhans, Webb Miller, Katherine Aylor Fisher, Jiang Du, Hadar H. Sheffer, Sarah Djebali, Frank Doyle, Nathan Lamarre-Vincent, Chia-Lin Wei, Laura A.L. Dillon, Jennifer Harrow, Robert C. Altshuler, Tyler Alioto, Raymond K. Auerbach, Adam Frankish, Rebekka O. Sprouse, Patrick J. Collins, E. Christopher Partridge, Zheng Liu, Yoichiro Shibata, Elliott H. Margulies, Abigail K. Ebersol, Kimberly A. Showers, Eric D. Green, Krishna M. Roskin, Job Dekker, Barbara N. Pusey, Ekta Khurana, Gilberto DeSalvo, Yijun Ruan, Hao Wang, Jainab Khatun, Henriette O'Geen, Alexej Abyzov, Brian Williams, Ryan M. McDaniell, Maya Kasowski, Manoj Hariharan, Felix Kokocinski, Gloria Despacio-Reyes, Zhancheng Zhang, Subhradip Karmakar, Ewan Birney, Koon-Kiu Yan, Xian Chen, Shinny Vong, Daniel Sobral, Nick Bild, Seul K.C. Kim, Timo Lassmann, Li Wang, Minerva E. Sanchez, Vaughan Roach, Theodore Gibson, Stephen C. J. Parker, Michael F. Lin, Patrick A. Navas, Laurence R. Meyer, Luiz O. F. Penalva, Bradley E. Bernstein, Kevin P. White, Emilie Aït Yahya Graison, Juan M. Vaquerizas, Sushma Iyengar, Kimberly M. Newberry, Akshay Bhinge, Xiaolan Zhang, Kim Bell, Yoshihide Hayashizaki, Lucas Lochovsky, Noam Shoresh, Hagen Tilgner, Philip Cayting, Dorrelyn Patacsil, Timothy E. Reddy, Eric Haugen, Katherine E. Varley, M. van Baren, Nathan D. Trinklein, Bum Kyu Lee, Tristan Frum, Marianne Lindahl-Allen, Timothy Durham, Roderic Guigó, Christopher W. Maier, Micha Sammeth, Debasish Raha, Timothy R. Dreszer, Benedict Paten, Robbyn Issner, Michael R. Brent, Kevin Y. Yip, Kim Blahnik, Jason Ernst, Zhiping Weng, Henry Amrhein, Arend Sidow, Javier Herrero, Hui Gao, Stephen G. Landt, Pouya Kheradpour, Galt P. Barber, Gregory E. Crawford, Toby Hunt, HudsonAlpha Institute for Biotechnology [Huntsville, AL], ENCODE Project Consortium : Myers RM, Stamatoyannopoulos J, Snyder M, Dunham I, Hardison RC, Bernstein BE, Gingeras TR, Kent WJ, Birney E, Wold B, Crawford GE, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Mikkelsen TS, Kheradpour P, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Lin MF, Kellis M, Gingeras TR, Davis CA, Kapranov P, Dobin A, Zaleski C, Schlesinger F, Batut P, Chakrabortty S, Jha S, Lin W, Drenkow J, Wang H, Bell K, Gao H, Bell I, Dumais E, Dumais J, Antonarakis SE, Ucla C, Borel C, Guigo R, Djebali S, Lagarde J, Kingswood C, Ribeca P, Sammeth M, Alioto T, Merkel A, Tilgner H, Carninci P, Hayashizaki Y, Lassmann T, Takahashi H, Abdelhamid RF, Hannon G, Fejes-Toth K, Preall J, Gordon A, Sotirova V, Reymond A, Howald C, Graison E, Chrast J, Ruan Y, Ruan X, Shahab A, Ting Poh W, Wei CL, Crawford GE, Furey TS, Boyle AP, Sheffield NC, Song L, Shibata Y, Vales T, Winter D, Zhang Z, London D, Wang T, Birney E, Keefe D, Iyer VR, Lee BK, McDaniell RM, Liu Z, Battenhouse A, Bhinge AA, Lieb JD, Grasfeder LL, Showers KA, Giresi PG, Kim SK, Shestak C, Myers RM, Pauli F, Reddy TE, Gertz J, Partridge EC, Jain P, Sprouse RO, Bansal A, Pusey B, Muratet MA, Varley KE, Bowling KM, Newberry KM, Nesmith AS, Dilocker JA, Parker SL, Waite LL, Thibeault K, Roberts K, Absher DM, Wold B, Mortazavi A, Williams B, Marinov G, Trout D, Pepke S, King B, McCue K, Kirilusha A, DeSalvo G, Fisher-Aylor K, Amrhein H, Vielmetter J, Sherlock G, Sidow A, Batzoglou S, Rauch R, Kundaje A, Libbrecht M, Margulies EH, Parker SC, Elnitski L, Green ED, Hubbard T, Harrow J, Searle S, Kokocinski F, Aken B, Frankish A, Hunt T, Despacio-Reyes G, Kay M, Mukherjee G, Bignell A, Saunders G, Boychenko V, Van Baren M, Brown RH, Khurana E, Balasubramanian S, Zhang Z, Lam H, Cayting P, Robilotto R, Lu Z, Guigo R, Derrien T, Tanzer A, Knowles DG, Mariotti M, James Kent W, Haussler D, Harte R, Diekhans M, Kellis M, Lin M, Kheradpour P, Ernst J, Reymond A, Howald C, Graison EA, Chrast J, Tress M, Rodriguez JM, Snyder M, Landt SG, Raha D, Shi M, Euskirchen G, Grubert F, Kasowski M, Lian J, Cayting P, Lacroute P, Xu Y, Monahan H, Patacsil D, Slifer T, Yang X, Charos A, Reed B, Wu L, Auerbach RK, Habegger L, Hariharan M, Rozowsky J, Abyzov A, Weissman SM, Gerstein M, Struhl K, Lamarre-Vincent N, Lindahl-Allen M, Miotto B, Moqtaderi Z, Fleming JD, Newburger P, Farnham PJ, Frietze S, O'Geen H, Xu X, Blahnik KR, Cao AR, Iyengar S, Stamatoyannopoulos JA, Kaul R, Thurman RE, Wang H, Navas PA, Sandstrom R, Sabo PJ, Weaver M, Canfield T, Lee K, Neph S, Roach V, Reynolds A, Johnson A, Rynes E, Giste E, Vong S, Neri J, Frum T, Johnson EM, Nguyen ED, Ebersol AK, Sanchez ME, Sheffer HH, Lotakis D, Haugen E, Humbert R, Kutyavin T, Shafer T, Dekker J, Lajoie BR, Sanyal A, James Kent W, Rosenbloom KR, Dreszer TR, Raney BJ, Barber GP, Meyer LR, Sloan CA, Malladi VS, Cline MS, Learned K, Swing VK, Zweig AS, Rhead B, Fujita PA, Roskin K, Karolchik D, Kuhn RM, Haussler D, Birney E, Dunham I, Wilder SP, Keefe D, Sobral D, Herrero J, Beal K, Lukk M, Brazma A, Vaquerizas JM, Luscombe NM, Bickel PJ, Boley N, Brown JB, Li Q, Huang H, Gerstein M, Habegger L, Sboner A, Rozowsky J, Auerbach RK, Yip KY, Cheng C, Yan KK, Bhardwaj N, Wang J, Lochovsky L, Jee J, Gibson T, Leng J, Du J, Hardison RC, Harris RS, Song G, Miller W, Haussler D, Roskin K, Suh B, Wang T, Paten B, Noble WS, Hoffman MM, Buske OJ, Weng Z, Dong X, Wang J, Xi H, Tenenbaum SA, Doyle F, Penalva LO, Chittur S, Tullius TD, Parker SC, White KP, Karmakar S, Victorsen A, Jameel N, Bild N, Grossman RL, Snyder M, Landt SG, Yang X, Patacsil D, Slifer T, Dekker J, Lajoie BR, Sanyal A, Weng Z, Whitfield TW, Wang J, Collins PJ, Trinklein ND, Partridge EC, Myers RM, Giddings MC, Chen X, Khatun J, Maier C, Yu Y, Gunawardena H, Risk B, Feingold EA, Lowdon RF, Dillon LA, Good PJ, Harrow J, Searle S., Becker, Peter B, Broad Institute of MIT and Harvard, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Physics, Kellis, Manolis, Epstein, Charles B., Bernstein, Bradley E., Shoresh, Noam, Ernst, Jason, Mikkelsen, Tarjei Sigurd, Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Ward, Lucas D., Altshuler, Robert Charles, Lin, Michael F., ENCODE Project Consortium, Antonarakis, Stylianos, and Miotto, Benoit

Subjects
RNA, Messenger/genetics, [SDV]Life Sciences [q-bio], Messenger, Genoma humà, Genome, Medical and Health Sciences, 0302 clinical medicine, Models, ddc:576.5, Biology (General), Conserved Sequence, Genetics, 0303 health sciences, General Neuroscience, RNA-Binding Proteins, Genomics, Biological Sciences, Chromatin, 3. Good health, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Gene Components, 030220 oncology & carcinogenesis, DNA methylation, Encyclopedia, HIV/AIDS, Proteïnes de la sang -- Aspectes genètics, General Agricultural and Biological Sciences, Databases, Nucleic Acid, Human, Research Article, Quality Control, Process (engineering), QH301-705.5, 1.1 Normal biological development and functioning, Computational biology, Biology, ENCODE, General Biochemistry, Genetics and Molecular Biology, Chromatin/metabolism, Vaccine Related, 03 medical and health sciences, Databases, Genetic, Underpinning research, Humans, RNA, Messenger, RNA-Binding Proteins/genetics/metabolism, Vaccine Related (AIDS), Gene, 030304 developmental biology, Internet, General Immunology and Microbiology, Nucleic Acid, Agricultural and Veterinary Sciences, Base Sequence, Models, Genetic, Genome, Human, Prevention, Human Genome, Computational Biology, DNA Methylation, ENCODE Project Consortium, Gene Expression Regulation, DNA-Binding Proteins/genetics/metabolism, RNA, Human genome, Immunization, Generic health relevance, Developmental Biology
Abstract

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., National Human Genome Research Institute (U.S.), National Institutes of Health (U.S.)

Published
2011

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