ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries

The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This p...

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Bibliographic Details
Published in:PloS one 2012-08, Vol.7 (8), p.e39573-e39573
Main Authors: Nair, Nishanth Ulhas, Sahu, Avinash Das, Bucher, Philipp, Moret, Bernard M E
Format: Article
Language:English
Subjects:
Analysis
Animals
Bias
Binding sites
Bioinformatics
Biology
Cells, Cultured
Chromatin
Computer programs
Deoxyribonucleic acid
DNA
DNA methylation
Gene expression
Genes
Genomes
Genomics
Histones - chemistry
Histones - genetics
Histones - metabolism
Laboratories
Libraries
Mathematics
Methods
Mice
Models, Theoretical
Noise
Normalizing (statistics)
Peptide Library
Protein Processing, Post-Translational - physiology
Software
Statistical methods
Statistics
Stem cells
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Summary:The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039573