The Annals of Applied Statistics

Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains

Mengjie Chen, Haifan Lin, and Hongyu Zhao

Full-text: Open access

Abstract

Histone modification is a vital epigenetic mechanism for transcriptional control in eukaryotes. High-throughput techniques have enabled whole-genome analysis of histone modifications in recent years. However, most studies assume one combination of histone modification invariantly translates to one transcriptional output regardless of local chromatin environment. In this study we hypothesize that the genome is organized into local domains that manifest a similar enrichment pattern of histone modification, which leads to orchestrated regulation of expression of genes with relevant biological functions. We propose a multivariate Bayesian Change Point (BCP) model to segment the Drosophila melanogaster genome into consecutive blocks on the basis of combinatorial patterns of histone marks. By modeling the sparse distribution of histone marks with a zero-inflated Gaussian mixture, our partitions capture local BLOCKs that manifest a relatively homogeneous enrichment pattern of histone marks. We further characterized BLOCKs by their transcription levels, distribution of genes, degree of co-regulation and GO enrichment. Our results demonstrate that these BLOCKs, although inferred merely from histone modifications, reveal a strong relevance with physical domains, which suggest their important roles in chromatin organization and coordinated gene regulation.

Article information

Source
Ann. Appl. Stat., Volume 10, Number 1 (2016), 506-526.

Dates
Received: May 2014
Revised: August 2015
First available in Project Euclid: 25 March 2016

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1458909925

Digital Object Identifier
doi:10.1214/16-AOAS905

Mathematical Reviews number (MathSciNet)
MR3480505

Zentralblatt MATH identifier
1358.62088

Keywords
Bayesian change point model Histone modification chromosomal domain

Citation

Chen, Mengjie; Lin, Haifan; Zhao, Hongyu. Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains. Ann. Appl. Stat. 10 (2016), no. 1, 506--526. doi:10.1214/16-AOAS905. https://projecteuclid.org/euclid.aoas/1458909925


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