A mammalian methylation array for profiling methylation levels at conserved sequences

Author:

Arneson Adriana,Haghani Amin,Thompson Michael J.ORCID,Pellegrini Matteo,Kwon Soo BinORCID,Vu Ha,Maciejewski Emily,Yao Mingjia,Li Caesar Z.ORCID,Lu Ake T.,Morselli MarcoORCID,Rubbi Liudmilla,Barnes Bret,Hansen Kasper D.,Zhou Wanding,Breeze Charles E.ORCID,Ernst JasonORCID,Horvath SteveORCID

Abstract

AbstractInfinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

National Science Foundation

UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Ablon Scholars Program

Paul G. Allen Family Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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