Oct 30, 2018

Accurate prediction of cell composition, age, smoking consumption and infection serostatus based on blood DNA methylation profiles

BioRxiv : the Preprint Server for Biology
Jacob BergstedtEtienne Patin

Abstract

DNA methylation is a stable epigenetic alteration that plays a key role in cellular differentiation and gene regulation, and that has been proposed to mediate environmental effects on disease risk. Epigenome-wide association studies have identified and replicated associations between methylation sites and several disease conditions, which could serve as biomarkers in predictive medicine and forensics. Nevertheless, heterogeneity in cellular proportions between the compared groups could complicate interpretation. Reference-based cell-type deconvolution methods have proven useful in correcting epigenomic studies for cellular heterogeneity, but they rely on reference libraries of sorted cells and only predict a limited number of cell populations. Here we leverage >850,000 methylation sites included in the MethylationEPIC array and use elastic net regularized and stability selected regression models to predict the circulating levels of 70 blood cell subsets, measured by standardized flow cytometry in 962 healthy donors of western European descent. We show that our predictions, based on a hundred of methylation sites or lower, are less error-prone than other existing methods, and extend the number of cell types that can be accuratel...Continue Reading

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Mentioned in this Paper

Biological Markers
Genome-Wide Association Study
Study
Flow Cytometry
DNA Methylation [PE]
Protein Methylation
Pathogenic Organism
Environment
DNA Methylation
Cell Differentiation Process

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