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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\u2019 immune, metabolic and neurological phenotypes. By streamlining DNA methylation array analysis for undesigned genomes, our methods extend epigenome research to broad species contexts.<\/jats:p>","DOI":"10.1093\/bib\/bbac617","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T01:56:35Z","timestamp":1673229395000},"source":"Crossref","is-referenced-by-count":44,"title":["Comparative epigenome analysis using Infinium DNA methylation BeadChips"],"prefix":"10.1093","volume":"24","author":[{"given":"Wubin","family":"Ding","sequence":"first","affiliation":[{"name":"Center for Computational and Genomic Medicine, The Children\u2019s Hospital of Philadelphia , PA, 19104 , USA"}]},{"given":"Diljeet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, The Children\u2019s Hospital of Philadelphia , PA, 19104 , USA"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[{"name":"Dept. of Human Genetics, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA, 90095 , USA"},{"name":"Altos Labs , San Diego, CA , USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9126-1932","authenticated-orcid":false,"given":"Wanding","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, The Children\u2019s Hospital of Philadelphia , PA, 19104 , USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA, 19104 , USA"}]}],"member":"286","published-online":{"date-parts":[[2023,1,8]]},"reference":[{"key":"2023042822170486200_ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1098\/rstb.1990.0002","article-title":"DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes","volume":"326","author":"Bestor","year":"1990","journal-title":"Philos Trans R Soc Lond B Biol 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