Abstract
Abstract Recent advances in sequencing technologies and emerging single cell sequencing promise to profoundly impact cancer studies. One of the most important problems is reconstruction of history of cancer mutations. Existing methods model cells DNA as haplotypes and reconstruct perfect (or almost perfect) phylogeny of mutations from single cell DNA sequencing data. In this paper we propose to reconstruct genotypes (rather than haplotypes) which in absence of repeated and omitted mutations is equivalent to reconstruction of the mutation phylogeny. Single cell genotype reconstruction is proposed to perform in two steps - first the sequencing data are used for imputation of cell genotypes treated as individual human genomes and then the resulted genomes are fitted to perfect phylogeny by eliminating 4-gamete rule violations using integer linear programs. Our simulation results show advantage of single cell genotype imputation over existing methods. Note: This abstract was not presented at the meeting. Citation Format: Alex Zelikovsky, Igor Mandric, Pavel Skums, Ion Mandoiu, Bogdan Pasaniuc, Pramod Srivastava. Imputation of single cell cancer genotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-214.
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