A mammalian methylation array for profiling methylation levels at conserved sequences

A Arneson(University of California, Los Angeles), Amin Haghani(University of California, Los Angeles), Michael J. Thompson(University of California, Los Angeles), Matteo Pellegrini(University of California, Los Angeles), Soo Bin Kwon(University of California, Los Angeles), Ha Vu(University of California, Los Angeles), Emily Maciejewski(University of California, Los Angeles), M. Yao(University of California, Los Angeles), Caesar Z. Li(University of California, Los Angeles), Ake T. Lu(University of California, Los Angeles), Marco Morselli(University of California, Los Angeles), Liudmilla Rubbi(University of California, Los Angeles), Bret Barnes(Illumina (United States)), Kasper D. Hansen(Johns Hopkins University), Wanding Zhou(Children's Hospital of Philadelphia), Charles E. Breeze(Altius Institute for Biomedical Sciences), Jason Ernst(University of California, Los Angeles), Steve Horvath(University of California, Los Angeles)
Nature Communications
February 10, 2022
10.1038/s41467-022-28355-z
Cited by 213Open Access
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Abstract

Infinium 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.

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