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
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H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions
Yichao Cai,Ying Zhang,Yan Ping Loh,Jia Qi Tng,Mei Chee Lim,Zhendong Cao,Anandhkumar Raju,Shang Li,Lakshmanan Manikandan,Vinay Tergaonkar,Greg Tucker-Kellogg,Melissa J. Fullwood +11 more
TL;DR: H3K 27me3-rich regions of the genome defined from clusters of H3K27me3 peaks may be used to identify silencers that can regulate gene expression via proximity or looping and their mechanisms of functioning via looping are characterized.
Posted ContentDOI
Basset: Learning the regulatory code of the accessible genome with deep convolutional neural networks.
TL;DR: An open source package Basset is introduced to apply CNNs to learn the functional activity of DNA sequences from genomics data and offers a powerful computational approach to annotate and interpret the noncoding genome.
Journal ArticleDOI
Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.
Matthias Heinig,Michiel E. Adriaens,Michiel E. Adriaens,Sebastian Schafer,Sebastian Schafer,Hanneke W. M. van Deutekom,Elisabeth M. Lodder,James S. Ware,James S. Ware,James S. Ware,Valentin Schneider,Leanne E. Felkin,Leanne E. Felkin,Esther E. Creemers,Benjamin Meder,Hugo A. Katus,Frank Rühle,Monika Stoll,Monika Stoll,François Cambien,François Cambien,Eric Villard,Eric Villard,Philippe Charron,Philippe Charron,András Varró,Nanette H. Bishopric,Alfred L. George,Alfred L. George,Cristobal G. dos Remedios,Aida Moreno-Moral,Francesco Pesce,Francesco Pesce,Anja Bauerfeind,Franz Rüschendorf,Carola Rintisch,Enrico Petretto,Paul J.R. Barton,Paul J.R. Barton,Stuart A. Cook,Yigal M. Pinto,Connie R. Bezzina,Norbert Hubner +42 more
TL;DR: RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors, and systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes.
Journal ArticleDOI
Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps
Valentina Iotchkova,Valentina Iotchkova,Jie Huang,John A. Morris,Deepti Jain,Caterina Barbieri,Caterina Barbieri,Klaudia Walter,Josine L. Min,Lu Chen,Lu Chen,William J. Astle,Massimilian Cocca,Patrick Deelen,Heather Elding,Aliki-Eleni Farmaki,Christopher S. Franklin,Mattias Frånberg,Tom R. Gaunt,Albert Hofman,Albert Hofman,Tao Jiang,Marcus E. Kleber,Genevieve Lachance,Jian'an Luan,Giovanni Malerba,Angela Matchan,Daniel Mead,Yasin Memari,Ioanna Ntalla,Ioanna Ntalla,Kalliope Panoutsopoulou,Raha Pazoki,John R. B. Perry,John R. B. Perry,Fernando Rivadeneira,Maria Sabater-Lleal,Bengt Sennblad,So-Youn Shin,So-Youn Shin,Lorraine Southam,Lorraine Southam,Michela Traglia,Freerk van Dijk,Elisabeth M. van Leeuwen,Gianluigi Zaza,Weihua Zhang,Najaf Amin,Adam S. Butterworth,Adam S. Butterworth,John C. Chambers,George Dedoussis,Abbas Dehghan,Oscar H. Franco,Lude Franke,Mattia Frontini,Giovanni Gambaro,Paolo Gasparini,Paolo Gasparini,Anders Hamsten,Aaron Issacs,Jaspal S. Kooner,Charles Kooperberg,Claudia Langenberg,Winfried März,Winfried März,Winfried März,Robert A. Scott,Morris A. Swertz,Daniela Toniolo,André G. Uitterlinden,Cornelia M. van Duijn,Hugh Watkins,Hugh Watkins,Eleftheria Zeggini,Mathew T Maurano,Nicholas J. Timpson,Alexander P. Reiner,Alexander P. Reiner,Paul L. Auer,Nicole Soranzo,Nicole Soranzo,Nicole Soranzo +82 more
TL;DR: Genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry is applied, followed by association analysis with 20 quantitative cardiometabolic and hematological traits, resulting in 17 new associations.
Journal ArticleDOI
A massively parallel reporter assay dissects the influence of chromatin structure on cis-regulatory activity.
TL;DR: This work presents a massively parallel reporter gene assay that measures the activities of hundreds of different CRSs, each integrated at many specific genomic locations, and explains the data with a quantitative model in which expression levels are set by independent contributions from local C RSs and the regional chromatin environment.
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