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Title: Broad-Enrich: functional interpretation of large sets of broad genomic regions.

Authors: Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A

Published In Bioinformatics, (2014 Sep 01)

Abstract: MOTIVATION: Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. RESULTS: To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. AVAILABILITY AND IMPLEMENTATION: http://broad-enrich.med.umich.edu for Web version and R package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PubMed ID: 25161225 Exiting the NIEHS site

MeSH Terms: Cell Line; Chromatin Immunoprecipitation/methods*; Genetic Loci; Genomics/methods*; High-Throughput Nucleotide Sequencing; Histones/metabolism*; Humans; Logistic Models; Sequence Analysis, DNA; Transcription Factors/metabolism

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