Open AccessJournal Article
Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types
Jason Ernst,Pouya Kheradpour,Pouya Kheradpour,Tarjei S. Mikkelsen,Noam Shoresh,Lucas D. Ward,Lucas D. Ward,Charles B. Epstein,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Manching Ku,Manching Ku,Manching Ku,Timothy Durham,Manolis Kellis,Manolis Kellis,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +20 more
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TLDR
This study presents a general framework for deciphering cis-regulatory connections and their roles in disease, and defines multi-cell activity profiles for chromatin state, gene expression, regulatory motif enrichment, and regulator expression.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.read more
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An integrated encyclopedia of DNA elements in the human genome.
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
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The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression.
Thomas Derrien,Rory Johnson,Giovanni Bussotti,Andrea Tanzer,Sarah Djebali,Hagen Tilgner,Gregory Guernec,David C. Martin,Angelika Merkel,David G. Knowles,Julien Lagarde,Lavanya Veeravalli,Xiaoan Ruan,Yijun Ruan,Timo Lassmann,Piero Carninci,James B. Brown,Leonard Lipovich,José M. González,Mark G. Thomas,Carrie A. Davis,Ramin Shiekhattar,Thomas R. Gingeras,Tim Hubbard,Cedric Notredame,Jennifer Harrow,Roderic Guigó +26 more
TL;DR: The most complete human lncRNA annotation to date is presented, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts, and expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes.
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DNA methylation age of human tissues and cell types
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Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
Moran N. Cabili,Cole Trapnell,Cole Trapnell,Loyal A. Goff,Magdalena J. Koziol,Magdalena J. Koziol,Barbara Tazon-Vega,Barbara Tazon-Vega,Aviv Regev,John L. Rinn,John L. Rinn +10 more
TL;DR: It is found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that l incRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes.
Journal ArticleDOI
Discovery and refinement of loci associated with lipid levels
Cristen J. Willer,Ellen M. Schmidt,Sebanti Sengupta,Gina M. Peloso,Gina M. Peloso,Gina M. Peloso,Stefan Gustafsson,Stavroula Kanoni,Andrea Ganna,Andrea Ganna,Jin Chen,Martin L. Buchkovich,Samia Mora,Jacques S. Beckmann,Jennifer L. Bragg-Gresham,Hsing-Yi Chang,Ayse Demirkan,Heleen M. den Hertog,Ron Do,Louise A. Donnelly,Georg Ehret,Georg Ehret,Tõnu Esko,Tõnu Esko,Mary F. Feitosa,Teresa Ferreira,Krista Fischer,Pierre Fontanillas,Ross M. Fraser,Daniel F. Freitag,Deepti Gurdasani,Deepti Gurdasani,Kauko Heikkilä,Elina Hyppönen,Aaron Isaacs,Anne U. Jackson,Åsa Johansson,Toby Johnson,Marika Kaakinen,Johannes Kettunen,Johannes Kettunen,Marcus E. Kleber,Marcus E. Kleber,Xiaohui Li,Jian'an Luan,Leo-Pekka Lyytikäinen,Patrik K. E. Magnusson,Massimo Mangino,Evelin Mihailov,May E. Montasser,Martina Müller-Nurasyid,Ilja M. Nolte,Jeffrey R. O'Connell,Cameron D. Palmer,Cameron D. Palmer,Markus Perola,Markus Perola,Markus Perola,Ann-Kristin Petersen,Serena Sanna,Richa Saxena,Sonia Shah,Dmitry Shungin,Dmitry Shungin,Carlo Sidore,Carlo Sidore,Ci Song,Ci Song,Rona J. Strawbridge,Ida Surakka,Ida Surakka,Toshiko Tanaka,Tanya M. Teslovich,Gudmar Thorleifsson,Evita G. Van Den Herik,Benjamin F. Voight,Kelly A. Volcik,Lindsay L. Waite,Andrew Wong,Ying Wu,Weihua Zhang,Weihua Zhang,Devin Absher,Gershim Asiki,Inês Barroso,Inês Barroso,Inês Barroso,Latonya F. Been,Jennifer L. Bolton,Lori L. Bonnycastle,Paolo Brambilla,Mary Susan Burnett,Giancarlo Cesana,Maria Dimitriou,Alex S. F. Doney,Angela Döring,Paul Elliott,Paul Elliott,Stephen E. Epstein,Gudmundur I. Eyjolfsson,Bruna Gigante,Mark O. Goodarzi,Harald Grallert,Martha L. Gravito,Christopher J. Groves,Göran Hallmans,Anna-Liisa Hartikainen,Caroline Hayward,Dena G. Hernandez,Andrew A. Hicks,Hilma Holm,Yi Jen Hung,Thomas Illig,Matthew Jones,Pontiano Kaleebu,John J.P. Kastelein,Kay-Tee Khaw,Eric Kim,Norman Klopp,Pirjo Komulainen,Meena Kumari,Claudia Langenberg,Terho Lehtimäki,Shih-Yi Lin,Jaana Lindström,Ruth J. F. Loos,Ruth J. F. Loos,François Mach,Wendy L. McArdle,Christa Meisinger,Braxton D. Mitchell,Gabrielle Müller,Ramaiah Nagaraja,Narisu Narisu,Tuomo Nieminen,Rebecca N. Nsubuga,Isleifur Olafsson,Ken K. Ong,Ken K. Ong,Aarno Palotie,Aarno Palotie,Theodore Papamarkou,Theodore Papamarkou,Theodore Papamarkou,Cristina Pomilla,Cristina Pomilla,Anneli Pouta,Anneli Pouta,Daniel J. Rader,Muredach P. Reilly,Paul M. Ridker,Fernando Rivadeneira,Igor Rudan,Aimo Ruokonen,Nilesh J. Samani,Nilesh J. Samani,Hubert Scharnagl,Janet Seeley,Janet Seeley,Kaisa Silander,Kaisa Silander,Alena Stančáková,Kathleen Stirrups,Amy J. Swift,Laurence Tiret,André G. Uitterlinden,L. Joost van Pelt,Sailaja Vedantam,Sailaja Vedantam,Nicholas W.J. Wainwright,Nicholas W.J. Wainwright,Cisca Wijmenga,Sarah H. Wild,Gonneke Willemsen,Tom Wilsgaard,James F. Wilson,Elizabeth H. Young,Elizabeth H. Young,Jing Hua Zhao,Linda S. Adair,Dominique Arveiler,Themistocles L. Assimes,Stefania Bandinelli,Franklyn I. Bennett,Murielle Bochud,Bernhard O. Boehm,Bernhard O. Boehm,Dorret I. Boomsma,Ingrid B. Borecki,Stefan R. Bornstein,Pascal Bovet,Michel Burnier,Harry Campbell,Aravinda Chakravarti,John C. Chambers,John C. Chambers,John C. Chambers,Yii-Der Ida Chen,Yii-Der Ida Chen,Francis S. Collins,Richard S. Cooper,John Danesh,George Dedoussis,Ulf de Faire,Alan B. Feranil,Jean Ferrières,Luigi Ferrucci,Nelson B. Freimer,Christian Gieger,Leif Groop,Leif Groop,Vilmundur Gudnason,Ulf Gyllensten,Anders Hamsten,Tamara B. Harris,Aroon D. Hingorani,Joel N. Hirschhorn,Joel N. Hirschhorn,Albert Hofman,G. Kees Hovingh,Chao A. Hsiung,Steve E. Humphries,Steven C. Hunt,Kristian Hveem,Carlos Iribarren,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Antti Jula,Mika Kähönen,Jaakko Kaprio,Jaakko Kaprio,Antero Kesäniemi,Mika Kivimäki,Jaspal S. Kooner,Jaspal S. Kooner,Jaspal S. Kooner,Peter J. Koudstaal,Ronald M. Krauss,Diana Kuh,Johanna Kuusisto,Kirsten Ohm Kyvik,Markku Laakso,Timo A. Lakka,Timo A. Lakka,Lars Lind,Cecilia M. Lindgren,Nicholas G. Martin,Winfried März,Winfried März,Winfried März,Mark I. McCarthy,Colin A. McKenzie,Pierre Meneton,Andres Metspalu,Leena Moilanen,Andrew D. Morris,Patricia B. Munroe,Inger Njølstad,Nancy L. Pedersen,Chris Power,Peter P. Pramstaller,Peter P. Pramstaller,Jackie F. Price,Bruce M. Psaty,Bruce M. Psaty,Thomas Quertermous,Rainer Rauramaa,Rainer Rauramaa,Danish Saleheen,Danish Saleheen,Veikko Salomaa,Dharambir K. Sanghera,Jouko Saramies,Peter Schwarz,Wayne Huey-Herng Sheu,Alan R. Shuldiner,Alan R. Shuldiner,Agneta Siegbahn,Tim D. Spector,Kari Stefansson,Kari Stefansson,David P. Strachan,Bamidele O. Tayo,Elena Tremoli,Jaakko Tuomilehto,Matti Uusitupa,Cornelia M. van Duijn,Peter Vollenweider,Lars Wallentin,Nicholas J. Wareham,John Whitfield,Bruce H. R. Wolffenbuttel,Jose M. Ordovas,Jose M. Ordovas,Eric Boerwinkle,Colin N. A. Palmer,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Daniel I. Chasman,Jerome I. Rotter,Paul W. Franks,Paul W. Franks,Paul W. Franks,Samuli Ripatti,Samuli Ripatti,Samuli Ripatti,L. Adrienne Cupples,L. Adrienne Cupples,Manjinder S. Sandhu,Manjinder S. Sandhu,Stephen S. Rich,Michael Boehnke,Panos Deloukas,Sekar Kathiresan,Sekar Kathiresan,Karen L. Mohlke,Erik Ingelsson,Erik Ingelsson,Gonçalo R. Abecasis +319 more
TL;DR: It is found that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index.
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TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
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Potential etiologic and functional implications of genome-wide association loci for human diseases and traits
Lucia A. Hindorff,Praveen Sethupathy,Heather Junkins,Erin M. Ramos,Jayashri P. Mehta,Francis S. Collins,Teri A. Manolio +6 more
TL;DR: An online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs) is developed, well-suited to guide future investigations of the role of common variants in complex disease etiology.
Journal ArticleDOI
Biological, clinical and population relevance of 95 loci for blood lipids
Tanya M. Teslovich,Kiran Musunuru,Albert V. Smith,Andrew C. Edmondson,Ioannis M. Stylianou,Masahiro Koseki,James P. Pirruccello,James P. Pirruccello,James P. Pirruccello,Samuli Ripatti,Daniel I. Chasman,Cristen J. Willer,Christopher T. Johansen,Sigrid W. Fouchier,Aaron Isaacs,Gina M. Peloso,Maja Barbalić,Sally L. Ricketts,Joshua C. Bis,Yurii S. Aulchenko,Gudmar Thorleifsson,Mary F. Feitosa,John C. Chambers,Marju Orho-Melander,Olle Melander,Toby Johnson,Xiaohui Li,Xiuqing Guo,Mingyao Li,Yoon Shin Cho,Min Jin Go,Young Jin Kim,Jong-Young Lee,Taesung Park,Kyunga Kim,Xueling Sim,Rick Twee-Hee Ong,Damien C. Croteau-Chonka,Leslie A. Lange,Joshua D. Smith,Kijoung Song,Jing Hua Zhao,Xin Yuan,Jian'an Luan,Claudia Lamina,Andreas Ziegler,Weihua Zhang,Robert Y.L. Zee,Alan F. Wright,Jacqueline C. M. Witteman,James F. Wilson,Gonneke Willemsen,H.-Erich Wichmann,John Whitfield,Dawn M. Waterworth,Nicholas J. Wareham,Gérard Waeber,Peter Vollenweider,Benjamin F. Voight,Benjamin F. Voight,Veronique Vitart,André G. Uitterlinden,Manuela Uda,Jaakko Tuomilehto,John R. Thompson,Toshiko Tanaka,Ida Surakka,Heather M. Stringham,Tim D. Spector,Nicole Soranzo,Nicole Soranzo,Johannes H. Smit,Juha Sinisalo,Kaisa Silander,Eric J.G. Sijbrands,Angelo Scuteri,James Scott,David Schlessinger,Serena Sanna,Veikko Salomaa,Juha Saharinen,Chiara Sabatti,Aimo Ruokonen,Igor Rudan,Lynda M. Rose,Robert Roberts,Mark J. Rieder,Bruce M. Psaty,Peter P. Pramstaller,Irene Pichler,Markus Perola,Brenda W.J.H. Penninx,Nancy L. Pedersen,Cristian Pattaro,Alex N. Parker,Guillaume Paré,Ben A. Oostra,Christopher J. O'Donnell,Markku S. Nieminen,Deborah A. Nickerson,Grant W. Montgomery,Thomas Meitinger,Ruth McPherson,Mark I. McCarthy,Wendy L. McArdle,David Masson,Nicholas G. Martin,Fabio Marroni,Massimo Mangino,Patrik K. E. Magnusson,Gavin Lucas,Robert Luben,Ruth J. F. Loos,Marja-Liisa Lokki,Guillaume Lettre,Claudia Langenberg,Lenore J. Launer,Edward G. Lakatta,Reijo Laaksonen,Kirsten Ohm Kyvik,Florian Kronenberg,Inke R. Koenig,Kay-Tee Khaw,Jaakko Kaprio,Lee M. Kaplan,Åsa Johansson,Marjo-Riitta Järvelin,A. Cecile J.W. Janssens,Erik Ingelsson,Wilmar Igi,G. Kees Hovingh,Jouke-Jan Hottenga,Albert Hofman,Andrew A. Hicks,Christian Hengstenberg,Iris M. Heid,Caroline Hayward,Aki S. Havulinna,Nicholas D. Hastie,Tamara B. Harris,Talin Haritunians,Alistair S. Hall,Ulf Gyllensten,Candace Guiducci,Leif Groop,Leif Groop,Elena Gonzalez,Christian Gieger,Nelson B. Freimer,Luigi Ferrucci,Jeanette Erdmann,Paul Elliott,Kenechi Ejebe,Angela Doering,Anna F. Dominiczak,Serkalem Demissie,Panagiotis Deloukas,Eco J. C. de Geus,Ulf de Faire,Gabriel Crawford,Francis S. Collins,Yii-Der Ida Chen,Mark J. Caulfield,Harry Campbell,Noël P. Burtt,Lori L. Bonnycastle,Dorret I. Boomsma,S. Matthijs Boekholdt,Richard N. Bergman,Inês Barroso,Stefania Bandinelli,Christie M. Ballantyne,Themistocles L. Assimes,Themistocles L. Assimes,Thomas Quertermous,Thomas Quertermous,David Altshuler,David Altshuler,Mark Seielstad,Tien Yin Wong,E-Shyong Tai,Alan B. Feranil,Christopher W. Kuzawa,Christopher W. Kuzawa,Linda S. Adair,Herman A. Taylor,Ingrid B. Borecki,Stacey Gabriel,James G. Wilson,Hilma Holm,Unnur Thorsteinsdottir,Vilmundur Gudnason,Ronald M. Krauss,Karen L. Mohlke,Jose M. Ordovas,Patricia B. Munroe,Jaspal S. Kooner,Alan R. Tall,Robert A. Hegele,John J.P. Kastelein,Eric E. Schadt,Jerome I. Rotter,Eric Boerwinkle,David P. Strachan,Vincent Mooser,Kari Stefansson,Muredach P. Reilly,Nilesh J. Samani,Heribert Schunkert,L. Adrienne Cupples,Manjinder S. Sandhu,Manjinder S. Sandhu,Paul M. Ridker,Daniel J. Rader,Cornelia M. van Duijn,Leena Peltonen,Gonçalo R. Abecasis,Michael Boehnke,Sekar Kathiresan +218 more
TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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