EpiDISH

EpiDISH is a software tool designed to address the challenges arising from intra-sample cellular heterogeneity when identifying biomarkers in large Epigenome-Wide Association Studies (EWAS). It achieves this by leveraging cell-type specific DNAse Hypersensitive Site (DHS) information from the NIH Epigenomics Roadmap to construct an improved reference DNA methylation database.

The software tool uses a combined algorithm that utilizes DHS data and robust partial correlations for inference, which leads to a marginal but statistically significant improvement of cell-count estimates in whole blood and mixtures involving epithelial cell types. EpiDISH provides a comparative evaluation of different reference-based algorithms for estimating cell-type fractions and subsequent inference in EWAS. It concludes that the widely-used constrained projection technique may not always be optimal. Instead, the method based on robust partial correlations is generally more robust across various tissue types and for realistic noise levels.

EpiDISH demonstrates the added value in estimating cell-type fractions and subsequent inference in EWAS of smoking. It is generally more robust across various tissue types and for realistic noise levels when compared to other reference-based algorithms such as constrained projection and CIBERSORT.