Open Access
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
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TLDR
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.Abstract:
The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.read more
Citations
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The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
Kristin G. Ardlie,David S. DeLuca,Ayellet V. Segrè,Timothy J. Sullivan,Taylor Young,Ellen Gelfand,Casandra A. Trowbridge,Julian Maller,Taru Tukiainen,Monkol Lek,Lucas D. Ward,Pouya Kheradpour,Benjamin Iriarte,Yan Meng,Cameron D. Palmer,Tõnu Esko,Wendy Winckler,Joel N. Hirschhorn,Manolis Kellis,Daniel G. MacArthur,Gad Getz,Andrey A. Shabalin,Gen Li,Yi-Hui Zhou,Andrew B. Nobel,Ivan Rusyn,Fred A. Wright,Tuuli Lappalainen,Pedro G. Ferreira,Halit Ongen,Manuel A. Rivas,Alexis Battle,Sara Mostafavi,Jean Monlong,Michael Sammeth,Marta Melé,Ferran Reverter,Jakob M. Goldmann,Daphne Koller,Roderic Guigó,Mark I. McCarthy,Emmanouil T. Dermitzakis,Eric R. Gamazon,Hae Kyung Im,Anuar Konkashbaev,Dan L. Nicolae,Nancy J. Cox,Timothée Flutre,Xiaoquan Wen,Matthew Stephens,Jonathan K. Pritchard,Zhidong Tu,Bin Zhang,Tao Huang,Quan Long,Luan Lin,Jialiang Yang,Jun Zhu,Jun Liu,Amanda Brown,Bernadette Mestichelli,Denee Tidwell,Edmund Lo,Mike Salvatore,Saboor Shad,Jeffrey A. Thomas,John T. Lonsdale,Michael T. Moser,Bryan Gillard,Ellen Karasik,Kimberly Ramsey,Christopher Choi,Barbara A. Foster,John Syron,Johnell Fleming,Harold Magazine,Rick Hasz,Gary Walters,Jason Bridge,Mark Miklos,Susan L. Sullivan,Laura Barker,Heather M. Traino,Maghboeba Mosavel,Laura A. Siminoff,Dana R. Valley,Daniel C. Rohrer,Scott D. Jewell,Philip A. Branton,Leslie H. Sobin,Mary Barcus,Liqun Qi,Jeffrey McLean,Pushpa Hariharan,Ki Sung Um,Shenpei Wu,David Tabor,Charles Shive,Anna M. Smith,Stephen A. Buia,Anita H. Undale,Karna Robinson,Nancy Roche,Kimberly M. Valentino,Angela Britton,Robin Burges,Debra Bradbury,Kenneth W. Hambright,John Seleski,Greg E. Korzeniewski,Kenyon Erickson,Yvonne Marcus,Jorge Tejada,Mehran Taherian,Chunrong Lu,Margaret J. Basile,Deborah C. Mash,Simona Volpi,Jeffery P. Struewing,Gary F. Temple,Joy T. Boyer,Deborah Colantuoni,Roger Little,Susan E. Koester,Latarsha J. Carithers,Helen M. Moore,Ping Guan,Carolyn C. Compton,Sherilyn Sawyer,Joanne P. Demchok,Jimmie B. Vaught,Chana A. Rabiner,Nicole C. Lockhart +132 more
TL;DR: The landscape of gene expression across tissues is described, thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants are cataloged, complex network relationships are described, and signals from genome-wide association studies explained by eQTLs are identified.
Journal ArticleDOI
deepTools2: a next generation web server for deep-sequencing data analysis
Fidel Ramírez,Devon Ryan,Björn Grüning,Vivek Bhardwaj,Fabian Kilpert,Andreas S. Richter,Steffen Heyne,Friederike Dündar,Thomas Manke +8 more
TL;DR: An update to the Galaxy-based web server deepTools, which allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches, is presented.
Journal ArticleDOI
Genetic effects on gene expression across human tissues.
Enhancing GTEx (eGTEx) groups,Nih Common Fund,Nhgri,Biospecimen Core Resource—VARI,Elsi study,Genome Browser Data Integration Visualization—EBI,Lead analysts,Alexis Battle,Christopher D. Brown,Barbara E. Engelhardt,Stephen B. Montgomery +10 more
TL;DR: It is found that local genetic variation affects gene expression levels for the majority of genes, and inter-chromosomal genetic effects for 93 genes and 112 loci are identified, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
Journal ArticleDOI
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Benjamin Izar,Sanjay M. Prakadan,Marc H. Wadsworth,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Ken Dutton-Regester,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Aleth Gaillard,Kellie E. Kolb,Alexandra-Chloé Villani,Cory M. Johannessen,Aleksandr Andreev,Eliezer M. Van Allen,Eliezer M. Van Allen,Monica M. Bertagnolli,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Charles H. Yoon,Charles H. Yoon,Orit Rozenblatt-Rosen,Alex K. Shalek,Aviv Regev,Aviv Regev,Aviv Regev,Levi A. Garraway +45 more
TL;DR: The cellular ecosystem of tumors is begin to unravel and how single-cell genomics offers insights with implications for both targeted and immune therapies is unraveled.
Journal ArticleDOI
10 Years of GWAS Discovery: Biology, Function, and Translation
Peter M. Visscher,Naomi R. Wray,Qian Zhang,Pamela Sklar,Mark I. McCarthy,Matthew A. Brown,Jian Yang +6 more
TL;DR: The remarkable range of discoveriesGWASs has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics are reviewed.
References
More filters
Journal ArticleDOI
High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development
Andrea Wilderman,Jennifer VanOudenhove,Jeffrey Kron,James P. Noonan,Justin Cotney,Justin Cotney +5 more
TL;DR: Significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period.
Journal ArticleDOI
A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.
Eric Conway,Emilia Jerman,Evan Healy,Shinsuke Ito,Daniel Holoch,Giorgio Oliviero,Orla Deevy,Eleanor Glancy,Darren J. Fitzpatrick,Marlena Mucha,Ariane Watson,Alan M. Rice,Paul Chammas,Christine S. Huang,Indigo Pratt-Kelly,Yoko Koseki,Manabu Nakayama,Tomoyuki Ishikura,Gundula Streubel,Kieran Wynne,Karsten Hokamp,Aoife McLysaght,Claudio Ciferri,Luciano Di Croce,Gerard Cagney,Raphaël Margueron,Haruhiko Koseki,Adrian P. Bracken +27 more
TL;DR: PALI1/2 potentially link polycombs with transcriptional co-repressors in the regulation of cellular identity during development and in cancer.
Journal ArticleDOI
Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types
TL;DR: A joint role of sequence motifs and specific chromatin states beyond mere accessibility in mediating regulator binding dynamics across different cell types is suggested, suggesting a much richer chromatin landscape beyond simple accessibility.
Journal ArticleDOI
Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability.
Lindsay F. Rizzardi,Peter Hickey,Varenka A. Rodriguez DiBlasi,Rakel Tryggvadottir,Colin M. Callahan,Adrian Idrizi,Kasper D. Hansen,Kasper D. Hansen,Andrew P. Feinberg +8 more
TL;DR: An extensive profile of DNA methylation in neuronal and non-neuronal cells across four brain regions is reported, showing that differential epigenetic marks are enriched for DNA variants associated with neuropsychiatric traits.
Journal ArticleDOI
Integration of human pancreatic islet genomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci.
Matthias Thurner,Martijn van de Bunt,Jason M. Torres,Anubha Mahajan,Vibe Nylander,Amanda J. Bennett,Kyle J. Gaulton,Amy Barrett,Carla Burrows,Christopher G. Bell,Christopher G. Bell,Robert Lowe,Stephan Beck,Vardhman K. Rakyan,Anna L. Gloyn,Anna L. Gloyn,Mark I. McCarthy,Mark I. McCarthy +17 more
TL;DR: For example, this article found that the enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant.