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
Reads0
Chats0
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
More filters
Journal ArticleDOI
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
One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin.
Alexej Abyzov,Alexej Abyzov,Livia Tomasini,Bo Zhou,Nikolaos Vasmatzis,Gianfilippo Coppola,Mariangela Amenduni,Reenal Pattni,Michael Wilson,Mark Gerstein,Sherman M. Weissman,Alexander E. Urban,Flora M. Vaccarino +12 more
TL;DR: A large degree of somatic mosaicism in healthy human tissues is revealed, which could be a characteristic of clonal cell selection, clonal expansion, or both, and de novo and cancer mutations to somatic mosaicicism are linked.
Journal ArticleDOI
Divergent neuronal DNA methylation patterns across human cortical development reveal critical periods and a unique role of CpH methylation
Amanda J. Price,Amanda J. Price,Leonardo Collado-Torres,Nikolay A. Ivanov,Wei Xia,Emily E. Burke,Joo Heon Shin,Ran Tao,Liang Ma,Yankai Jia,Thomas M. Hyde,Joel E. Kleinman,Daniel R. Weinberger,Andrew E. Jaffe +13 more
TL;DR: By profiling DNAm changes in NeuN-sorted neurons over the span of human cortical development, novel, dynamic regions of DNAm that would be masked in homogenate DNAm data are identified and enriched heritability for many phenotypes within identified DNAm features are found.
Journal ArticleDOI
Enhancing the Promise of Drug Repositioning through Genetics.
TL;DR: The approaches described in this review have the potential to provide a faster, cheaper and more certain route to clinical approval for drug repositioning.
Journal ArticleDOI
Critical threshold levels of DNA methyltransferase 1 are required to maintain DNA methylation across the genome in human cancer cells.
Yi Cai,Hsing-Chen Tsai,Ray Whay Chiu Yen,Yang W. Zhang,Xiangqian Kong,Wei Wang,Limin Xia,Stephen B. Baylin +7 more
TL;DR: It is shown that new approaches, like decreasing the DNMT targeting protein, UHRF1, can augment the DNA demethylation capacities of existing DNA methylation inhibitors for fully realizing their therapeutic potential.
Posted ContentDOI
Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression
TL;DR: The genetic findings were associated with clinical features ofMDD, and implicated prefrontal and anterior cingulate cortex in the pathophysiology of MDD (regions exhibiting anatomical differences between MDD cases and controls), and genes that are targets of antidepressant medications were strongly enriched for MDD association signals.