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- Title
A signal–noise model for significance analysis of ChIP-seq with negative control.
- Authors
Han Xu; Handoko, Lusy; Xueliang Wei; Chaopeng Ye; Jianpeng Sheng; Chia-Lin Wei; Feng Lin; Wing-Kin Sung; Dopazo, Joaquin
- Abstract
Motivation: ChIP-seq is becoming the main approach to the genome-wide study of protein--DNA interactions and histone modifications. Existing informatics tools perform well to extract strong ChIP-enriched sites. However, two questions remain to be answered: (i) to which extent is a ChIP-seq experiment able to reveal the weak ChIP-enriched sites? (ii) are the weak sites biologically meaningful? To answer these questions, it is necessary to identify the weak ChIP signals from background noise. Results: We propose a linear signal--noise model, in which a noise rate was introduced to represent the fraction of noise in a ChIP library. We developed an iterative algorithm to estimate the noise rate using a control library, and derived a library-swapping strategy for the false discovery rate estimation. These approaches were integrated in a general-purpose framework, named CCAT (Control-based ChIP-seq Analysis Tool), for the significance analysis of ChIP-seq. Applications to H3K4me3 and H3K36me3 datasets showed that CCAT predicted significantly more ChIP-enriched sites that the previous methods did. With the high sensitivity of CCAT prediction, we revealed distinct chromatin features associated to the strong and weak H3K4me3 sites.
- Publication
Bioinformatics, 2010, Vol 26, Issue 9, p1199
- ISSN
1367-4803
- Publication type
Academic Journal
- DOI
10.1093/bioinformatics/btq128