An approach of identifying differential nucleosome regions in multiple samples

Lingjie Liu, Jianming Xie, Xiao Sun, Kun Luo, Zhaohui Steve Qin, Hongde Liu

Nucleosome plays a role in transcriptional regulation through occluding the binding of proteins to DNA sites. Nucleosome occupancy varies among different cell types. Identification of such variation will help to understand regulation mechanism. The previous researches focused on the methods for two-sample comparison. However, a multiple-sample comparison (n ≥ 3) is necessary, especially in studying development and cancer. METHODS: Here, we proposed a Chi-squared test-based approach, named as Dimnp, to identify differential nucleosome regions (DNRs) in multiple samples. Dimnp is designed for sequenced reads data and includes the modules of both calling nucleosome occupancy and identifying DNRs. We validated Dimnp on dataset of the mutant strains in which the modifiable histone residues are mutated into alanine in Saccharomyces cerevisiae. Dimnp shows a good capacity (area under the curve > 0.87) compared with the manually identified DNRs. Just by one time, Dimnp is able to identify all the DNRs identified by two-sample method Danpos. Under a deviation of 40 bp, the matched DNRs are above 60% between Dimnp and Danpos. With Dimnp, we found that promoters and telomeres are highly dynamic upon mutating the modifiable histone residues. We developed a tool of identifying the DNRs in multiple samples and cell types. The tool can be applied in studying nucleosome variation in gradual change in development and cancer.