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Title: Improved regulatory element prediction based on tissue-specific local epigenomic signatures

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [3];  [4];  [4];  [2];  [5];  [6];  [7];  [8];  [9]
  1. Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037,, Bioinformatics Program, University of California, San Diego, La Jolla, CA 92093,
  2. Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093,
  3. Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
  4. Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037,
  5. Institute for Human Genetics, University of California, San Francisco, CA 94143,, Department of Neurology, University of California, San Francisco, CA 94143,
  6. Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, US Department of Energy Joint Genome Institute, Walnut Creek, CA 94598,, School of Natural Sciences, University of California, Merced, CA 95343,
  7. Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, US Department of Energy Joint Genome Institute, Walnut Creek, CA 94598,
  8. Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093,, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093,
  9. Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037,, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037

Accurate enhancer identification is critical for understanding the spatiotemporal transcriptional regulation during development as well as the functional impact of disease-related noncoding genetic variants. Computational methods have been developed to predict the genomic locations of active enhancers based on histone modifications, but the accuracy and resolution of these methods remain limited. Here, we present an algorithm, regulator y element prediction based on tissue-specific local epigenetic marks (REPTILE), which integrates histone modification and whole-genome cytosine DNA methylation profiles to identify the precise location of enhancers. We tested the ability of REPTILE to identify enhancers previously validated in reporter assays. Compared with existing methods, REPTILE shows consistently superior performance across diverse cell and tissue types, and the enhancer locations are significantly more refined. We show that, by incorporating base-resolution methylation data, REPTILE greatly improves upon current methods for annotation of enhancers across a variety of cell and tissue types.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); Gordon and Betty Moore Foundation
Grant/Contract Number:
AC02-05CH11231; U54 HG006997; K12 GM068524; GBMF3034; R01 MH094670; U01 MH105985; GC1R-06673-B
OSTI ID:
1343636
Alternate ID(s):
OSTI ID: 1393127
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 114 Journal Issue: 9; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 47 works
Citation information provided by
Web of Science

References (66)

Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape journal May 2016
A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly journal July 2003
High-Resolution Mapping and Characterization of Open Chromatin across the Genome journal January 2008
ChromHMM: automating chromatin-state discovery and characterization journal February 2012
Model-based Analysis of ChIP-Seq (MACS) journal January 2008
BEDOPS: high-performance genomic feature operations journal May 2012
Integrative analysis of haplotype-resolved epigenomes across human tissues journal February 2015
Charting a dynamic DNA methylation landscape of the human genome journal August 2013
Fast and accurate short read alignment with Burrows-Wheeler transform journal May 2009
Progress and challenges in bioinformatics approaches for enhancer identification journal December 2015
DNA methylation: roles in mammalian development journal February 2013
Functions of DNA methylation: islands, start sites, gene bodies and beyond journal May 2012
A desicion-theoretic generalization of on-line learning and an application to boosting book January 1995
9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response journal February 2011
Histone H3K27ac separates active from poised enhancers and predicts developmental state journal November 2010
Statistical methods for detecting differentially methylated loci and regions journal September 2014
DNA methylation patterns and epigenetic memory journal January 2002
Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb journal January 2005
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome journal February 2007
GENCODE: The reference human genome annotation for The ENCODE Project journal September 2012
Recruitment of CBP/p300 by the IFNβ Enhanceosome Is Required for Synergistic Activation of Transcription journal January 1998
Inferring regulatory element landscapes and transcription factor networks from cancer methylomes journal May 2015
Human body epigenome maps reveal noncanonical DNA methylation variation journal June 2015
Dynamic DNA methylation across diverse human cell lines and tissues journal January 2013
C/EBPβ (CEBPB) protein binding to the C/EBP|CRE DNA 8-mer TTGC|GTCA is inhibited by 5hmC and enhanced by 5mC, 5fC, and 5caC in the CG dinucleotide journal June 2015
Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues journal September 2013
Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position journal October 2013
Erratum: Corrigendum: DNA-binding factors shape the mouse methylome at distal regulatory regions journal April 2012
Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice journal April 1989
Prediction of promoters and enhancers using multiple DNA methylation-associated features journal June 2015
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease journal January 2005
RFECS: A Random-Forest Based Algorithm for Enhancer Identification from Chromatin State journal March 2013
Human DNA methylomes at base resolution show widespread epigenomic differences journal October 2009
Genome-wide discovery of human heart enhancers journal January 2010
An integrated encyclopedia of DNA elements in the human genome journal September 2012
The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer journal June 2009
Histone modifications at human enhancers reflect global cell-type-specific gene expression journal March 2009
The Human Genome Browser at UCSC journal May 2002
Establishing, maintaining and modifying DNA methylation patterns in plants and animals journal February 2010
ChIP–seq: advantages and challenges of a maturing technology journal September 2009
High-throughput mapping of regulatory DNA journal January 2016
Abnormalities in human pluripotent cells due to reprogramming mechanisms journal July 2014
DELTA: A Distal Enhancer Locating Tool Based on AdaBoost Algorithm and Shape Features of Chromatin Modifications journal June 2015
BEDTools: a flexible suite of utilities for comparing genomic features journal January 2010
In vivo enhancer analysis of human conserved non-coding sequences journal November 2006
Transcriptional enhancers in development and disease journal January 2012
Non-CG Methylation in the Human Genome journal August 2015
‘Leveling’ the playing field for analyses of single-base resolution DNA methylomes journal December 2012
Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits journal November 2016
Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells journal May 2013
PEDLA: predicting enhancers with a deep learning-based algorithmic framework journal June 2016
Integrating Diverse Datasets Improves Developmental Enhancer Prediction journal June 2014
Base-resolution methylation patterns accurately predict transcription factor bindings in vivo journal February 2015
VISTA Enhancer Browser--a database of tissue-specific human enhancers journal January 2007
Integrative analysis of 111 reference human epigenomes journal February 2015
A comparative encyclopedia of DNA elements in the mouse genome journal November 2014
Estimation of False Discovery Rate Using Sequential Permutation p -Values : Sequential Permutation journal February 2013
CTCF: an architectural protein bridging genome topology and function journal March 2014
Discover regulatory DNA elements using chromatin signatures and artificial neural network journal May 2010
Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains journal June 2016
Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities journal May 2010
Prediction of regulatory elements in mammalian genomes using chromatin signatures journal January 2008
Random Forests journal January 2001
Unsupervised pattern discovery in human chromatin structure through genomic segmentation journal March 2012
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA journal September 2012
Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome journal December 2015