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bioRxiv
BIORXIV
bioRxiv
Cold Spring Harbor Laboratory

10.1101/2024.05.17.594606
preprint
1
Article
MSA: scalable DNA methylation screening BeadChip for high-throughput trait association studies
Goldberg David C
Cloud Cameron
Lee Sol Moe
Barnes Bret
Gruber Steven
Kim Elliot
Pottekat Anita
Westphal Max
McAuliffe Luana
Majournie Elisa
KalayilManian Manesh
Zhu Qingdi
Tran Christine
Hansen Mark
Parker Jared B
Kohli Rahul M
Porecha Rishi
Renke Nicole
Zhou Wanding
21 5 2024
2024.05.17.594606http://biorxiv.org/lookup/doi/10.1101/2024.05.17.594606
nihpp-2024.05.17.594606.pdf
SUMMARY

The Infinium DNA Methylation BeadChips have significantly contributed to population-scale epigenetics research by enabling epigenome-wide trait association discoveries. Here, we design, describe, and experimentally verify a new iteration of this technology, the Methylation Screening Array (MSA), to focus on human trait screening and discovery. This array utilizes extensive data from previous Infinium platform-based epigenome-wide association studies (EWAS). It incorporates knowledge from the latest single-cell and cell type-resolution whole genome methylome profiles. The MSA is engineered to achieve scalable screening of epigenetics-trait association in an ultra-high sample throughput. Our design encompassed diverse human trait associations, including those with genetic, cellular, environmental, and demographical variables and human diseases such as genetic, neurodegenerative, cardiovascular, infectious, and immune diseases. We comprehensively evaluated this array’s reproducibility, accuracy, and capacity for cell-type deconvolution and supporting 5-hydroxymethylation profiling in diverse human tissues. Our first atlas data using this platform uncovered the complex chromatin and tissue contexts of DNA modification variations and genetic variants linked to human phenotypes.

Availability

Informatics for MSA data preprocessing and functional analysis is available in the R/Bioconductor package SeSAMe (version 3.22+): https://bioconductor.org/packages/release/bioc/html/sesame.html

The complete MSA manifest, design criteria, technical, human trait, and functional annotations are available at https://zwdzwd.github.io/InfiniumAnnotation

The generated human cell line, primary tissue methylome profiles (N=420), and EM-seq data are available in the Gene Expression Omnibus with accession GSE264438 and GSE267407.
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