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
Analysis of Transcriptional Variability in a Large Human iPSC Library Reveals Genetic and Non-genetic Determinants of Heterogeneity
Ivan Carcamo-Orive,Gabriel E. Hoffman,Paige Cundiff,Noam D. Beckmann,Sunita L. D’Souza,Joshua W. Knowles,Achchhe Patel,Dimitri Papatsenko,Dimitri Papatsenko,Fahim Abbasi,Gerald M. Reaven,Sean Whalen,Philip Lee,Mohammad Shahbazi,Marc Henrion,Kuixi Zhu,Sven Wang,Panos Roussos,Panos Roussos,Eric E. Schadt,Gaurav Pandey,Rui Chang,Thomas Quertermous,Ihor R. Lemischka +23 more
TL;DR: Network, pathway, and key driver analyses showed that Polycomb targets contribute significantly to the non-genetic variability seen within and across individuals, highlighting this chromatin regulator as a likely source of reprogramming-based variability.
Journal ArticleDOI
Identification of type 2 diabetes loci in 433,540 East Asian individuals
Cassandra N. Spracklen,Cassandra N. Spracklen,Momoko Horikoshi,Young Jin Kim,Kuang Lin,Fiona Bragg,Sanghoon Moon,Ken Suzuki,Claudia H. T. Tam,Yasuharu Tabara,Soo Heon Kwak,Fumihiko Takeuchi,Jirong Long,Victor Jun Yu Lim,Jin-Fang Chai,Chien-Hsiun Chen,Masahiro Nakatochi,Jie Yao,Jie Yao,Hyeok Sun Choi,Apoorva K Iyengar,Hannah J Perrin,Sarah M Brotman,Martijn van de Bunt,Anna L. Gloyn,Jennifer E. Below,Jennifer E. Below,Michael Boehnke,Donald W. Bowden,John C. Chambers,Anubha Mahajan,Anubha Mahajan,Mark I. McCarthy,Maggie C.Y. Ng,Maggie C.Y. Ng,Lauren E. Petty,Lauren E. Petty,Weihua Zhang,Weihua Zhang,Andrew P. Morris,Andrew P. Morris,Andrew P. Morris,Linda S. Adair,Masato Akiyama,Zheng Bian,Juliana C.N. Chan,Li-Ching Chang,Miao-Li Chee,Yii-Der Ida Chen,Yii-Der Ida Chen,Yuan-Tsong Chen,Zhengming Chen,Lee-Ming Chuang,Shufa Du,Penny Gordon-Larsen,Myron D. Gross,Xiuqing Guo,Xiuqing Guo,Yu Guo,Sohee Han,Annie-Green Howard,Wei Huang,Yi-Jen Hung,Yi-Jen Hung,Mi Yeong Hwang,Chii-Min Hwu,Chii-Min Hwu,Sahoko Ichihara,Masato Isono,Hye-Mi Jang,Guozhi Jiang,Jost B. Jonas,Yoichiro Kamatani,Tomohiro Katsuya,Takahisa Kawaguchi,Chiea Chuen Khor,Chiea Chuen Khor,Katsuhiko Kohara,Myung-Shik Lee,Myung-Shik Lee,Nanette R. Lee,Liming Li,Jianjun Liu,Jianjun Liu,Andrea O.Y. Luk,Jun Lv,Yukinori Okada,Mark A Pereira,Charumathi Sabanayagam,Shi Jinxiu,Dong Mun Shin,Wing-Yee So,Atsushi Takahashi,Brian Tomlinson,Brian Tomlinson,Fuu Jen Tsai,Rob M. van Dam,Yong-Bing Xiang,Ken Yamamoto,Toshimasa Yamauchi,Kyungheon Yoon,Canqing Yu,Jian-Min Yuan,Liang Zhang,Wei Zheng,Michiya Igase,Yoon Shin Cho,Jerome I. Rotter,Jerome I. Rotter,Ya Xing Wang,Wayne Huey-Herng Sheu,Wayne Huey-Herng Sheu,Mitsuhiro Yokota,Jer-Yuarn Wu,Ching-Yu Cheng,Tien Yin Wong,Xiao-Ou Shu,Norihiro Kato,Kyong-Soo Park,Kyong-Soo Park,Kyong-Soo Park,E-Shyong Tai,Fumihiko Matsuda,Woon-Puay Koh,Ronald Cw Ma,Shiro Maeda,Iona Y Millwood,Ju Young Lee,Takashi Kadowaki,Robin G. Walters,Bong-Jo Kim,Karen L. Mohlke,Xueling Sim +132 more
TL;DR: A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2abetes in both East Asian and European populations.
Journal ArticleDOI
Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits.
Yang Wu,Jian Zeng,Futao Zhang,Zhihong Zhu,Ting Qi,Zhili Zheng,Zhili Zheng,Luke R. Lloyd-Jones,Riccardo E. Marioni,Nicholas G. Martin,Grant W. Montgomery,Ian J. Deary,Naomi R. Wray,Peter M. Visscher,Allan F. McRae,Jian Yang +15 more
TL;DR: Using the SMR & HEIDI method to integrate GWAS, eQTL and mQTL data, Wu et al. map DNA methylation sites to the transcriptome and thereby prioritize functionally relevant genes for 12 human complex traits.
Journal ArticleDOI
Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Douglas H. Phanstiel,Douglas H. Phanstiel,Kevin Van Bortle,Damek V. Spacek,Gaelen T. Hess,Muhammad S. Shamim,Muhammad S. Shamim,Ido Machol,Ido Machol,Michael I. Love,Erez Lieberman Aiden,Erez Lieberman Aiden,Michael C. Bassik,Michael Snyder +13 more
TL;DR: It is demonstrated that dynamic looping events are regulatory rather than structural in nature and widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops is uncovered.
Journal ArticleDOI
A CRISPR-dCas Toolbox for Genetic Engineering and Synthetic Biology.
Xiaoshu Xu,Lei S. Qi +1 more
TL;DR: This review summarizes current applications of the dCas tools for transcription regulation, epigenetic engineering, genome imaging, genetic screens, and chromatin immunoprecipitation and highlights the advantages and existing challenges.
References
More filters
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal ArticleDOI
Gene Ontology: tool for the unification of biology
M Ashburner,Catherine A. Ball,Judith A. Blake,David Botstein,Heather Butler,J. M. Cherry,Allan Peter Davis,Kara Dolinski,Selina S. Dwight,J.T. Eppig,Midori A. Harris,David P. Hill,Laurie Issel-Tarver,Andrew Kasarskis,Suzanna E. Lewis,John C. Matese,Joel E. Richardson,M. Ringwald,Gerald M. Rubin,Gavin Sherlock +19 more
TL;DR: The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.
Journal ArticleDOI
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks
Paul Shannon,Andrew Markiel,Owen Ozier,Nitin S. Baliga,Jonathan T. Wang,Daniel Ramage,Nada Amin,Benno Schwikowski,Trey Ideker +8 more
TL;DR: Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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 ArticleDOI
Model-based Analysis of ChIP-Seq (MACS)
Yong Zhang,Tao Liu,Clifford A. Meyer,Jérôme Eeckhoute,David S. Johnson,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,Richard M. Myers,Myles Brown,Wei Li,X. Shirley Liu +11 more
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.