Title: Reconstruction of clone- and haplotype-specific cancer genomes karyotypes from tumor mixtures
Presenter: Sergey Aganezov, PhD, CBI
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Abstract: We introduce a novel method, Reconstructing Cancer Karotypes (RCK), for reconstructing one or more rearranged cancer genomes, or clones, that best explain the read alignments from a bulk tumor sample. RCK leverages specific evolutionary constraints on the somatic mutation process in cancer in order to reduce ambiguity in the deconvolution of admixed DNA sequence data into multiple haplotype-specific cancer clones. In particular, RCK relies on the infinite sites assumption that a genome rearrangement is highly unlikely to occur at the same nucleotide position more than once during somatic evolution. Earlier methods for analyzing cancer genome rearrangements (e.g.PREGO,Weaver,andReMixT) rely on weaker forms on the infinite sites assumption that do not account for the diploid nature of the human genome and the presence of multiple clones within a tumor. As a result, we show that these other methods can yield highly improbable reconstructions.