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Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases
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TLDR
In this article, the authors developed a comprehensive resource of 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes.Abstract:
Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type– and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants—including variants that do not reach genome-wide significance—often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).read more
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Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Hana Lango Allen,Karol Estrada,Guillaume Lettre,Sonja I. Berndt,Michael N. Weedon,Fernando Rivadeneira,Cristen J. Willer,Anne U. Jackson,Sailaja Vedantam,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Maegi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Toby Johnson,Shamika Ketkar,Peter Kraft,Massimo Mangino,Inga Prokopenko,Devin Absher,Eva Albrecht,Florian Ernst,Nicole L. Glazer,Caroline Hayward,Jouke-Jan Hottenga,Kevin B. Jacobs,Joshua W. Knowles,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Markus Perola,John R. B. Perry,Ida Surakka,Mari-Liis Tammesoo,Elizabeth L. Altmaier,Najaf Amin,Thor Aspelund,Tushar Bhangale,Gabrielle Boucher,Daniel I. Chasman,Constance Chen,Lachlan J. M. Coin,Mark E. Cooper,Anna L. Dixon,Quince Gibson,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Inke R. Koenig,Tony Kwan,Robert Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Mueller,Julius S. Ngwa,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,Michael C. Turchin,Liesbeth Vandenput,Dominique J. Verlaan,Veronique Vitart,Charles C. White,Andreas Ziegler,Peter Almgren,Anthony J. Balmforth,Harry Campbell,Lorena Citterio,Alessandro De Grandi,Anna F. Dominiczak,Jubao Duan,Paul Elliott,Roberto Elosua,Johan G. Eriksson,Nelson B. Freimer,Eco J. C. de Geus,Nicola Glorioso,Shen Haiqing,Anna-Liisa Hartikainen,Aki S. Havulinna,Andrew A. Hicks,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpelaeinen,Markku Koiranen,Ivana Kolcic,Seppo Koskinen,Peter Kovacs,Jaana Laitinen,Jianjun Liu,Marja-Liisa Lokki,Ana Marušić,Andrea Maschio,Thomas Meitinger,Antonella Mulas,Guillaume Paré,Alex N. Parker,John F. Peden,Astrid Petersmann,Irene Pichler,Kirsi H. Pietiläinen,Anneli Pouta,Martin Riddertrale,Jerome I. Rotter,Jennifer G. Sambrook,Alan R. Sanders,Carsten Oliver Schmidt,Juha Sinisalo,Jan Smit,Heather M. Stringham,G. Bragi Walters,Elisabeth Widen,Sarah H. Wild,Gonneke Willemsen,Laura Zagato,Lina Zgaga,Paavo Zitting,Helene Alavere,Martin Farrall,Wendy L. McArdle,Mari Nelis,Marjolein Peters,Samuli Ripatti,Joyce B. J. vVan Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,Richard N. Bergman,Sven Bergmann,Francis S. Collins,Daniele Cusi,Martin den Heijer,Gudny Eiriksdottir,Pablo V. Gejman,Alistair S. Hall,Anders Hamsten,Heikki V. Huikuri,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Toenjes,Jaakko Tuomilehto,Gert-Jan B. van Ommen,Jorma Viikari,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael A. Province,Manfred Kayser,Alice M. Arnold,Larry D. Atwood,Eric Boerwinkle,Stephen J. Chanock,Panos Deloukas,Christian Gieger,Henrik Grönberg,Per Hall,Andrew T. Hattersley,Christian Hengstenberg,Wolfgang Hoffman,G. Mark Lathrop,Veikko Salomaa,Stefan Schreiber,Manuela Uda,Dawn M. Waterworth,Alan F. Wright,Themistocles L. Assimes,Inês Barroso,Albert Hofman,Karen L. Mohlke,Dorret I. Boomsma,Mark J. Caulfield,L. Adrienne Cupples,Jeanette Erdmann,Caroline S. Fox,Vilmundur Gudnason,Ulf Gyllensten,Tamara B. Harris,Richard B. Hayes,Marjo-Ritta Jarvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Nilesh J. Samani,Tim D. Spector,Henry Voelzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H. Erich Schadt,Unnur Thorsteinsdottir,Leena Peltonen,André G. Uitterlinden,Peter M. Visscher,Nilanjan Chatterjee,Ruth J. F. Loos,Michael Boehnke,Mark I. McCarthy,Erik Ingelsson,Cecilia M. Lindgren,Gonçalo R. Abecasis,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn +289 more
TL;DR: In this paper, the authors show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, revealing patterns with important implications for genetic studies of common human diseases and traits.
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Multi-omics approaches to disease.
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iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data
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Integrative omics for health and disease.
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References
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Journal ArticleDOI
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.
Journal Article
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.
Journal ArticleDOI
Biological insights from 108 schizophrenia-associated genetic loci
Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Aiden Corvin,James T.R. Walters,Kai-How Farh,Peter Holmans,Phil Lee,Phil Lee,Brendan Bulik-Sullivan,Brendan Bulik-Sullivan,David A. Collier,David A. Collier,Hailiang Huang,Hailiang Huang,Tune H. Pers,Tune H. Pers,Tune H. Pers,Ingrid Agartz,Ingrid Agartz,Esben Agerbo,Esben Agerbo,Margot Albus,Madeline Alexander,Farooq Amin,Silviu Alin Bacanu,Martin Begemann,Richard A. Belliveau,Judit Bene,Sarah E. Bergen,Sarah E. Bergen,Elizabeth Bevilacqua,Tim B. Bigdeli,Donald W. Black,Richard Bruggeman,Nancy G. Buccola,Randy L. Buckner,William Byerley,Wiepke Cahn,Guiqing Cai,Dominique Campion,Rita M. Cantor,Vaughan J. Carr,Noa Carrera,Stanley V. Catts,Kimberly Chambert,Raymond C.K. Chan,Ronald Y.L. Chen,Eric Y.H. Chen,Wei Cheng,Eric F.C. Cheung,Siow Ann Chong,C. Robert Cloninger,David Cohen,Nadine Cohen,Paul Cormican,Nicholas John Craddock,James J. Crowley,David Curtis,David Curtis,Michael Davidson,Kenneth L. Davis,Franziska Degenhardt,Jurgen Del Favero,Ditte Demontis,Ditte Demontis,Dimitris Dikeos,Timothy G. Dinan,Srdjan Djurovic,Gary Donohoe,Gary Donohoe,Elodie Drapeau,Jubao Duan,Frank Dudbridge,Naser Durmishi,Peter Eichhammer,Johan G. Eriksson,Johan G. Eriksson,Valentina Escott-Price,Laurent Essioux,Ayman H. Fanous,Martilias S. Farrell,Josef Frank,Lude Franke,Robert Freedman,Nelson B. Freimer,Marion Friedl,Joseph I. Friedman,Menachem Fromer,Menachem Fromer,Menachem Fromer,Giulio Genovese,Lyudmila Georgieva,Ina Giegling,Ina Giegling,Paola Giusti-Rodríguez,Stephanie Godard,Jacqueline I. Goldstein,Jacqueline I. Goldstein,Vera Golimbet,Srihari Gopal,Jacob Gratten,Lieuwe de Haan,Christian Hammer,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Vahram Haroutunian,Vahram Haroutunian,Annette M. Hartmann,Frans Henskens,Stefan Herms,Stefan Herms,Joel N. Hirschhorn,Joel N. Hirschhorn,Per Hoffmann,Per Hoffmann,A. Hofman,Mads V. Hollegaard,David M. Hougaard,Masashi Ikeda,Inge Joa,Antonio Julià,René S. Kahn,Luba Kalaydjieva,Sena Karachanak-Yankova,Juha Karjalainen,David J. Kavanagh,Matthew C. Keller,James L. Kennedy,Andrey Khrunin,Yunjung Kim,Janis Klovins,James A. Knowles,Bettina Konte,Vaidutis Kučinskas,Zita Ausrele Kucinskiene,Hana Kuzelova-Ptackova,Anna K. Kähler,Claudine Laurent,Jimmy Lee Chee Keong,S. Hong Lee,Sophie E. Legge,Bernard Lerer,Miaoxin Li,Tao Li,Kung-Yee Liang,Jeffrey A. Lieberman,Svetlana A. Limborska,Carmel M. Loughland,Jan Lubinski,Jouko Lönnqvist,Milan Macek,Patrik K. E. Magnusson,Brion S. Maher,Wolfgang Maier,J. Mallet,Sara Marsal,Manuel Mattheisen,Manuel Mattheisen,Manuel Mattheisen,Morten Mattingsdal,Robert W. McCarley,Colm McDonald,Andrew M. McIntosh,Sandra Meier,Carin J. Meijer,Béla Melegh,Ingrid Melle,Raquelle I. Mesholam-Gately,Andres Metspalu,Patricia T. Michie,Lili Milani,Vihra Milanova,Younes Mokrab,Derek W. Morris,Derek W. Morris,Ole Mors,Ole Mors,Kieran C. Murphy,Robin M. Murray,Inez Myin-Germeys,Bertram Mueller-Myhsok,Mari Nelis,Igor Nenadic,Deborah A. Nertney,Gerald Nestadt,Kristin K. Nicodemus,Liene Nikitina-Zake,Laura Nisenbaum,Annelie Nordin,Eadbhard O'Callaghan,Colm O'Dushlaine,F. Anthony O'Neill,Sang-Yun Oh,Ann Olincy,Line Olsen,Jim van Os,Jim van Os,Christos Pantelis,George N. Papadimitriou,Sergi Papiol,Elena Parkhomenko,Michele T. Pato,Tiina Paunio,Tiina Paunio,Milica Pejovic-Milovancevic,Diana O. Perkins,Olli Pietiläinen,Olli Pietiläinen,Jonathan Pimm,Andrew Pocklington,John Powell,Alkes L. Price,Alkes L. Price,Ann E. Pulver,Shaun Purcell,Digby Quested,Henrik B. Rasmussen,Abraham Reichenberg,Mark Reimers,Alexander Richards,Joshua L. Roffman,Panos Roussos,Douglas M. Ruderfer,Douglas M. Ruderfer,Veikko Salomaa,Alan R. Sanders,Ulrich Schall,Christian R. Schubert,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Edward M. Scolnick,Rodney J. Scott,Larry J. Seidman,Jianxin Shi,Engilbert Sigurdsson,Teimuraz Silagadze,Jeremy M. Silverman,Jeremy M. Silverman,Kang Sim,Petr Slominsky,Jordan W. Smoller,Jordan W. Smoller,Hon-Cheong So,Chris C. A. Spencer,Eli A. Stahl,Eli A. Stahl,Hreinn Stefansson,Stacy Steinberg,Elisabeth Stögmann,Richard E. Straub,Eric Strengman,Jana Strohmaier,T. Scott Stroup,Mythily Subramaniam,Jaana Suvisaari,Dragan M. Svrakic,Jin P. Szatkiewicz,Erik Söderman,Srinivas Thirumalai,Draga Toncheva,Sarah Tosato,Juha Veijola,John L. Waddington,Dermot Walsh,Dai Wang,Qiang Wang,Bradley T. Webb,Mark Weiser,Dieter B. Wildenauer,Nigel Williams,Stephanie Williams,Stephanie H. Witt,Aaron R. Wolen,Emily H. M. Wong,Brandon Wormley,Hualin Simon Xi,Clement C. Zai,Xuebin Zheng,Fritz Zimprich,Naomi R. Wray,Kari Stefansson,Peter M. Visscher,Rolf Adolfsson,Ole A. Andreassen,Douglas Blackwood,Elvira Bramon,Joseph D. Buxbaum,Anders D. Børglum,Anders D. Børglum,Sven Cichon,Sven Cichon,Ariel Darvasi,Enrico Domenici,Hannelore Ehrenreich,Tõnu Esko,Tõnu Esko,Tõnu Esko,Pablo V. Gejman,Michael Gill,Hugh Gurling,Christina M. Hultman,Nakao Iwata,Assen Jablensky,Erik G. Jönsson,Erik G. Jönsson,Kenneth S. Kendler,George Kirov,Jo Knight,Todd Lencz,Todd Lencz,Douglas F. Levinson,Qingqin S. Li,Jianjun Liu,Jianjun Liu,Anil K. Malhotra,Anil K. Malhotra,Steven A. McCarroll,Steven A. McCarroll,Andrew McQuillin,Jennifer L. Moran,Preben Bo Mortensen,Preben Bo Mortensen,Bryan J. Mowry,Markus M. Noethen,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Aarno Palotie,Aarno Palotie,Aarno Palotie,Carlos N. Pato,Tracey L. Petryshen,Tracey L. Petryshen,Danielle Posthuma,Danielle Posthuma,Marcella Rietschel,Brien P. Riley,Dan Rujescu,Dan Rujescu,Pak C. Sham,Pamela Sklar,David St Clair,Daniel R. Weinberger,Jens R. Wendland,Thomas Werge,Thomas Werge,Mark J. Daly,Mark J. Daly,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan +354 more
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
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The relationship between Precision-Recall and ROC curves
Jesse Davis,Mark Goadrich +1 more
TL;DR: It is shown that a deep connection exists between ROC space and PR space, such that a curve dominates in R OC space if and only if it dominates in PR space.
Journal ArticleDOI
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.