期刊
BIOINFORMATICS
卷 31, 期 12, 页码 1889-1896出版社
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btv094
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资金
- National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000454]
- National Human Genome Research Institute of the National Institutes of Health [R01 HG005119]
- National Institute of General Medical Sciences of the National Institutes of Health [P01 GM085354]
Motivation: ChIP-seq is a powerful technology to measure the protein binding or histone modification strength in the whole genome scale. Although there are a number of methods available for single ChIP-seq data analysis (e.g. 'peak detection'), rigorous statistical method for quantitative comparison of multiple ChIP-seq datasets with the considerations of data from control experiment, signal to noise ratios, biological variations and multiple-factor experimental designs is underdeveloped. Results: In this work, we develop a statistical method to perform quantitative comparison of multiple ChIP-seq datasets and detect genomic regions showing differential protein binding or histone modification. We first detect peaks from all datasets and then union them to form a single set of candidate regions. The read counts from IP experiment at the candidate regions are assumed to follow Poisson distribution. The underlying Poisson rates are modeled as an experiment-specific function of artifacts and biological signals. We then obtain the estimated biological signals and compare them through the hypothesis testing procedure in a linear model framework. Simulations and real data analyses demonstrate that the proposed method provides more accurate and robust results compared with existing ones.
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