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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Accurate promoter and enhancer identification in 127 ENCODE and roadmap epigenomics cell types and tissues by GenoSTAN.
Benedikt Zacher,Margaux Michel,Björn Schwalb,Patrick Cramer,Achim Tresch,Achim Tresch,Julien Gagneur +6 more
TL;DR: The proposed GenoSTAN (Genomic STate ANnotation) provides an easy-to-use tool to define promoters and enhancers in any system, and the annotation of human transcriptional cis-regulatory elements constitutes a rich resource for future research in biology and medicine.
Journal ArticleDOI
Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes
Qingbo Wang,Qingbo Wang,Emma Pierce-Hoffman,Beryl B. Cummings,Beryl B. Cummings,Jessica Alföldi,Jessica Alföldi,Laurent C. Francioli,Laurent C. Francioli,Laura D. Gauthier,Andrew J. Hill,Andrew J. Hill,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Genome Aggregation Database Production Team,Genome Aggregation Database Production Team,Konrad J. Karczewski,Konrad J. Karczewski,Daniel G. MacArthur +18 more
TL;DR: The gnomAD dataset is used to assemble a catalogue of MNVs and the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - are estimated.
Journal ArticleDOI
Efficient Generation of Transcriptomic Profiles by Random Composite Measurements
TL;DR: In this paper, the similarity between pairs of expression profiles can be approximated with very few composite measurements, and by leveraging sparse, modular representations of gene expression, they can use random composite measurements to recover high-dimensional gene expression levels (with 100 times fewer measurements than genes).
Posted ContentDOI
An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum
Yang Eric Li,Sebastian Preissl,Xiaomeng Hou,Ziyang Zhang,Kai Zhang,Rongxin Fang,Yunjiang Qiu,Olivier Poirion,Bin Li,Yiming Yan,Hanqing Liu,Xinxin Wang,Jee Yun Han,Jacinta Lucero,Samantha Kuan,David U. Gorkin,Michael Nunn,Eran A. Mukamel,M. Margarita Behrens,Joseph R. Ecker,Bing Ren +20 more
TL;DR: The accessible chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei is probed, and the resulting data is used to define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types.
Journal ArticleDOI
Into the Wild: GWAS Exploration of Non-coding RNAs.
TL;DR: The upcoming of databases integrating single-nucleotide polymorphisms (SNPs) and non-coding RNAs together with novel technologies will hopefully facilitate the discovery of causal non-Coding variants associated to disease.
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