recountmethylationenables flexible analysis of public blood DNA methylation array data

Abstract

Thousands of DNA methylation (DNAm) array samples from human blood are publicly available on the Gene Expression Omnibus (GEO), but they remain underutilized for experiment planning, replication, and cross-study and cross-platform analyses. To facilitate these tasks, we augmented our recountmethylation R/Bioconductor package with 12,537 uniformly processed EPIC and HM450K blood samples on GEO as well as several new features. We subsequently used our updated package in several illustrative analyses, finding (1) study ID bias adjustment increased variation explained by biological and demographic variables, (2) most variation in autosomal DNAm was explained by genetic ancestry and CD4+ T-cell fractions, and (3) the dependence of power to detect differential methylation on sample size was similar for each of peripheral blood mononuclear cells (PBMC), whole blood, and umbilical cord blood. Finally, we used PBMC and whole blood to perform independent validations, and we recovered 38-46% of differentially methylated probes (DMPs) between sexes from two previously published epigenome-wide association studies (EWAS).

Ultrasensitive amplification-free quantification of a methyl CpG-rich cancer biomarker by single-molecule kinetic fingerprinting

“…Maden et al published an R/Bioconductor package called “recountmethylation,” allowing easy access to preprocessed methylation beta values measured by the Illumina Infinium MethylationEPIC microarray (EPIC array). Using recountmethylation, we compiled methylation beta values at the BCAT1 promoter from 12,392 samples on blood samples available in GEO 42 . On the EPIC array, three degenerate cg probes are available within the 102 nt BCAT1 promoter ( Fig.…”

“…8). 42 . On the EPIC array, three degenerate cg probes are available within the 102 nt BCAT1 promoter (Fig.…”

“…Compilation of blood DNA methylation using recountmethylation. Recountmethylation is a R/Bioconductor package with 12, 537 uniformly processed EPIC and HM450K blood samples from GEO 42,51 .…”

“…Recountmethylation is a R/Bioconductor package with 12, 537 uniformly processed EPIC and HM450K blood samples from GEO 42, 51 . All data on GEO as of December of 2022 measured by Illumina EPIC array and Illumina HM450K array are compiled and made available on its public data server (https://recount.bio/data/).…”