An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data
An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data
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DOI：
10.1093/bioinformatics/btn402
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发表时间：
2008-10-15
期刊：
影响因子：
5.8
通讯作者：
Sung, Wing-Kin
中科院分区：
文献类型：
--
作者：
Xu, Han;Wei, Chia-Lin;Sung, Wing-Kin
动机：表观遗传修饰是调控基因表达和基因组功能的关键因素之一。在不同的表观遗传修饰中，差异组蛋白修饰位点（DHMS）是研究不同细胞类型、阶段或环境响应的表观遗传和基因表达调控的动态本质的重要研究对象。为了在全基因组规模上捕获组蛋白修饰，ChIP-seq技术正在成为一种强大而全面的方法。因此，通过比较两个ChIP-seq文库，DHMS可能是可识别的。然而，在这个问题上已经解决了literature.Results：针对确定DHMS，我们提出了一种方法，称为ChIPDiff的全基因组比较的组蛋白修饰位点的ChIP-seq。基于ChIP片段计数的观察，所提出的方法采用隐马尔可夫模型（HMM）来推断每个基因组位置处的组蛋白修饰变化的状态。我们通过比较小鼠胚胎干细胞（ESC）和神经祖细胞（NPC）之间的H3 K27 me 3修饰位点来评估ChIPDiff的性能。我们证明了我们的方法鉴定的H3 K27 me 3 DHMS具有高灵敏度，特异性和技术重现性。进一步应用ChIPDiff来揭示不同细胞状态之间的差异H3 K4 me 3和H3 K36 me 3位点。在我们的研究中，从这种比较中获得了有趣的生物学发现。
Motivation: Epigenetic modifications are one of the critical factors to regulate gene expression and genome function. Among different epigenetic modifications, the differential histone modification sites (DHMSs) are of great interest to study the dynamic nature of epigenetic and gene expression regulations among various cell types, stages or environmental responses. To capture the histone modifications at whole genome scale, ChIP-seq technology is becoming a robust and comprehensive approach. Thus the DHMSs are potentially identifiable by comparing two ChIP-seq libraries. However, little has been addressed on this issue in literature.Results: Aiming at identifying DHMSs, we propose an approach called ChIPDiff for the genome-wide comparison of histone modification sites identified by ChIP-seq. Based on the observations of ChIP fragment counts, the proposed approach employs a hidden Markov model (HMM) to infer the states of histone modification changes at each genomic location. We evaluated the performance of ChIPDiff by comparing the H3K27me3 modification sites between mouse embryonic stem cell (ESC) and neural progenitor cell (NPC). We demonstrated that the H3K27me3 DHMSs identified by our approach are of high sensitivity, specificity and technical reproducibility. ChIPDiff was further applied to uncover the differential H3K4me3 and H3K36me3 sites between different cell states. Interesting biological discoveries were achieved from such comparison in our study.