MSA: Scalable DNA methylation BeadChip for human trait screening

We designed and introduced a new methylation array concentrating on human trait screening and discovery. The new MSA (Methylation Screening Array) leveraged the massive Infinium platform-based data from epigenome-wide association studies, combined with updated knowledge from the latest single cell and cell type-resolution whole genome methylome profiles, 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, biological, and demographical variables, environmental exposures, and common human diseases such as neurodegenerative, genetic, cardiovascular, infectious, and immune diseases. We comprehensively evaluated this array's reproducibility, accuracy, and capacity in supporting 5-hydroxymethylation profiling and comprehensive cell-type deconvolution in diverse human tissues. Our first data using this platform uncovered dynamic chromatin and tissue contexts of DNA modification variations and genetic variants with human trait associations. Cell line (GM12878, K562, LNCaP, HeLa, Raji, MCF7, Jurkat, HCT116 and other Coriell cell lines), and 25 human tissue (Adrenal, Bladder, Cerebellum, Colon, Esophagus, Eye, Heart, Kidney, Larynx, Liver, Lung, Lymph Node, Motor cortex, Ovary, PBMC, Pancreas, Placenta, Prostate, Skin, Spinal Cord, Spleen, Stomach, Testis, Thymus, Thyroid, Trachea) and purified cell DNA (CD4+ T cells, CD8+ T cells, total T cell, NK cells, monocytes) and methylation titration control DNA is run on the MSA BeadChip to evaluate MSA reproducibility, accuracy, performance at low input ranges, and capability at capturing biological methylation variation. Tissues including cerebellum, motor cortex, colon, pancreas, skin, heart are additionally processed with bACE conversion to obtain 5hmC profiles.