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Abstract:
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Cancer progression is driven by both somatic copy number aberrations (CNAs) and chromatin remodeling, yet little is known about the interplay between these two classes of events in shaping the diversity of tumor cell lineages. In this talk I will present a new method, Alleloscope, for allele-specific copy number estimation that can be applied to single cell DNA and ATAC sequencing data, separately or in combination. Alleloscope enables integrative multi-omic analysis of allele-specific copy number and chromatin accessibility for the same cell. On scDNA-seq data from gastric, colorectal, and breast cancer samples, with extensive validation using matched linked-read sequencing, Alleloscope finds pervasive occurrence of highly complex, multi-allelic copy number aberrations, where cells that carry varying allelic configurations adding to the same total copy number co-evolve within a tumor. The contributions of such allele-specific events to intratumor heterogeneity have been under-reported and under-studied due to the lack of methods for their detection. On scATAC-seq from two basal cell carcinoma samples and a gastric cancer cell line, Alleloscope detects multi-allelic copy number ev
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