Copy number-aware methylation deconvolution analysis of cancers using whole genome bisulfite sequencing data

Le résumé fourni par la source

Aberrant DNA methylation is a molecular feature of metastatic castration-resistant prostate cancer (mCRPC). Although whole genome bisulfite sequencing (WGBS) of bulk tumors is widely used to reveal aberrant methylation at base-pair resolution, bulk tumor methylation signals are confounded by sample-specific variation in tumor purity and ploidy. We developed CAMDAC to address these confounders [2] and present an extension of this method for WGBS analysis. Applied to mCRPC samples, CAMDAC provides pure tumor methylation estimates at each CpG site, increasing our power to detect tumor-normal differential methylation events in cancer evolution. We use SNV-phased reads to demonstrate that CAMDAC-deconvolved methylation rates are superior to bulk methylation. Furthermore, we demonstrate the use of normal tissue methylation panels for deconvolution in the absence of patient-matched normal tissue and use EpiSCORE to highlight sources of heterogeneity between normal reference panels used for deconvolution. CAMDAC is an R package publicly available at https://github.com/VanLoo-lab/CAMDAC/.

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