Comparative epigenome analysis using Infinium DNA methylation BeadChips

Author:

Ding Wubin1,Kaur Diljeet1,Horvath Steve23,Zhou Wanding14ORCID

Affiliation:

1. Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia , PA, 19104 , USA

2. Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA, 90095 , USA

3. Altos Labs , San Diego, CA , USA

4. Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA, 19104 , USA

Abstract

Abstract The arrival of the Infinium DNA methylation BeadChips for mice and other nonhuman mammalian species has outpaced the development of the informatics that supports their use for epigenetics study in model organisms. Here, we present informatics infrastructure and methods to allow easy DNA methylation analysis on multiple species, including domesticated animals and inbred laboratory mice (in SeSAMe version 1.16.0+). First, we developed a data-driven analysis pipeline covering species inference, genome-specific data preprocessing and regression modeling. We targeted genomes of 310 species and 37 inbred mouse strains and showed that genome-specific preprocessing prevents artifacts and yields more accurate measurements than generic pipelines. Second, we uncovered the dynamics of the epigenome evolution in different genomic territories and tissue types through comparative analysis. We identified a catalog of inbred mouse strain-specific methylation differences, some of which are linked to the strains’ immune, metabolic and neurological phenotypes. By streamlining DNA methylation array analysis for undesigned genomes, our methods extend epigenome research to broad species contexts.

Funder

NIH

NIGMS

Children's Hospital of Philadelphia

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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