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ChIPnorm: A Statistical Method for Normalizing and Identifying Differential Regions in Histone Modification ChIP-seq Libraries

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  • Nishanth Ulhas Nair
  • Avinash Das Sahu
  • Philipp Bucher
  • Bernard M E Moret

Abstract

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.

Suggested Citation

  • Nishanth Ulhas Nair & Avinash Das Sahu & Philipp Bucher & Bernard M E Moret, 2012. "ChIPnorm: A Statistical Method for Normalizing and Identifying Differential Regions in Histone Modification ChIP-seq Libraries," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-14, August.
  • Handle: RePEc:plo:pone00:0039573
    DOI: 10.1371/journal.pone.0039573
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    Cited by:

    1. Zhaohui Qin & Ben Li & Karen N. Conneely & Hao Wu & Ming Hu & Deepak Ayyala & Yongseok Park & Victor X. Jin & Fangyuan Zhang & Han Zhang & Li Li & Shili Lin, 2016. "Statistical Challenges in Analyzing Methylation and Long-Range Chromosomal Interaction Data," Statistics in Biosciences, Springer;International Chinese Statistical Association, vol. 8(2), pages 284-309, October.

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