Journal ArticleDOI
Reconstruction of enhancer–target networks in 935 samples of human primary cells, tissues and cell lines
Qin Cao,Christine Anyansi,Christine Anyansi,Xihao Hu,Liangliang Xu,Lei Xiong,Wenshu Tang,Myth T.S. Mok,Chao Cheng,Xiaodan Fan,Mark Gerstein,Alfred S. L. Cheng,Kevin Y. Yip +12 more
TLDR
This work proposes a new method for determining the target genes of transcriptional enhancers in specific cells and tissues, and discovers three major co-regulation modes of enhancers and finds defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors.Abstract:
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.read more
Citations
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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
TL;DR: 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.
Journal ArticleDOI
Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations.
Charles P. Fulco,Charles P. Fulco,Joseph Nasser,Thouis R. Jones,Glen Munson,Drew T. Bergman,Vidya Subramanian,Sharon R. Grossman,Sharon R. Grossman,Rockwell Anyoha,Benjamin R. Doughty,Tejal A. Patwardhan,Tung T. Nguyen,Michael Kane,Elizabeth M. Perez,Neva C. Durand,Caleb A. Lareau,Elena K. Stamenova,Erez Lieberman Aiden,Eric S. Lander,Eric S. Lander,Eric S. Lander,Jesse M. Engreitz,Jesse M. Engreitz +23 more
TL;DR: A simple activity-by-contact model substantially outperformed previous methods at predicting the complex connections in the CRISPR dataset and allows systematic mapping of enhancer–gene connections in a given cell type, on the basis of chromatin-state measurements.
Journal ArticleDOI
Genome-wide enhancer maps link risk variants to disease genes
Joseph Nasser,Drew T. Bergman,Charles P. Fulco,Charles P. Fulco,Philine Guckelberger,Philine Guckelberger,Benjamin R. Doughty,Benjamin R. Doughty,Tejal A. Patwardhan,Tejal A. Patwardhan,Thouis R. Jones,Tung T. Nguyen,Jacob C. Ulirsch,Jacob C. Ulirsch,Fritz Lekschas,Kristy Mualim,Heini M. Natri,Elle M. Weeks,Glen Munson,Michael Kane,Helen Y. Kang,Ang Cui,Ang Cui,John P. Ray,John P. Ray,Thomas Eisenhaure,Ryan L. Collins,Ryan L. Collins,Kushal K. Dey,Hanspeter Pfister,Alkes L. Price,Alkes L. Price,Charles B. Epstein,Anshul Kundaje,Ramnik J. Xavier,Mark J. Daly,Hailiang Huang,Hailiang Huang,Hilary K. Finucane,Hilary K. Finucane,Nir Hacohen,Nir Hacohen,Eric S. Lander,Jesse M. Engreitz,Jesse M. Engreitz +44 more
TL;DR: In this article, the activity-by-contact (ABC) model was applied to create enhancer-gene maps in 131 human cell types and tissues, and use these maps to interpret the functions of GWAS variants.
Journal ArticleDOI
An atlas of dynamic chromatin landscapes in mouse fetal development
David U. Gorkin,David U. Gorkin,Iros Barozzi,Iros Barozzi,Yuan Zhao,Yuan Zhao,Yanxiao Zhang,Hui Huang,Hui Huang,Ah Young Lee,Bin Li,Joshua Chiou,Andre Wildberg,Bo Ding,Bo Zhang,Mengchi Wang,J. Seth Strattan,Jean M. Davidson,Yunjiang Qiu,Yunjiang Qiu,Veena Afzal,Jennifer A. Akiyama,Ingrid Plajzer-Frick,Catherine S. Novak,Momoe Kato,Tyler H. Garvin,Quan T. Pham,Anne N. Harrington,Brandon J. Mannion,Elizabeth Lee,Yoko Fukuda-Yuzawa,Yupeng He,Yupeng He,Sebastian Preissl,Sebastian Preissl,Sora Chee,Jee Yun Han,Brian A. Williams,Diane Trout,Henry Amrhein,Hongbo Yang,J. Michael Cherry,Wei Wang,Kyle J. Gaulton,Joseph R. Ecker,Yin Shen,Diane E. Dickel,Axel Visel,Axel Visel,Axel Visel,Len A. Pennacchio,Len A. Pennacchio,Len A. Pennacchio,Bing Ren +53 more
TL;DR: Analysis of chromatin state and accessibility in mouse tissues from twelve sites and eight developmental stages provides the most comprehensive view of Chromatin dynamics to date.
Journal ArticleDOI
SEdb: a comprehensive human super-enhancer database.
Yong Jiang,Fengcui Qian,Xuefeng Bai,Yuejuan Liu,Qiuyu Wang,Bo Ai,Xiaole Han,Shanshan Shi,Jian Zhang,Xuecang Li,Zhidong Tang,Qi Pan,Yuezhu Wang,Fan Wang,Chunquan Li +14 more
TL;DR: A comprehensive human super-enhancer database (SEdb, http://www.licpathway.net/sedb) that aimed to provide a large number of available resources on humansuper-enhancers was developed that was annotated with potential functions of super- enhancer in the gene regulation.
References
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
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Posted ContentDOI
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Journal ArticleDOI
The Human Genome Browser at UCSC
W. James Kent,Charles W. Sugnet,Terrence S. Furey,Krishna M. Roskin,Tom H. Pringle,Alan M. Zahler,and David Haussler +6 more
TL;DR: A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu.
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Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
Erez Lieberman Aiden,Nynke L. van Berkum,Louise Williams,Maxim Imakaev,Tobias Ragoczy,Tobias Ragoczy,Agnes Telling,Agnes Telling,Ido Amit,Bryan R. Lajoie,Peter J. Sabo,Michael O. Dorschner,Richard Sandstrom,Bradley E. Bernstein,Bradley E. Bernstein,Michaël Bender,Mark Groudine,Mark Groudine,Andreas Gnirke,John A. Stamatoyannopoulos,Leonid A. Mirny,Eric S. Lander,Eric S. Lander,Job Dekker +23 more
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