Allele-Specific Quantification of Structural Variations in Cancer Genomes

Overview

Journal Cell Syst

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Jul 26

PMID 27453446

Citations 25

Authors

Yang Li

Shiguo Zhou

David C Schwartz

Jian Ma

Affiliations

Soon will be listed here.

Abstract

Aneuploidy and structural variations (SVs) generate cancer genomes containing a mixture of rearranged genomic segments with extensive somatic copy number alterations. However, existing methods can identify either SVs or allele-specific copy number alterations but not both simultaneously, which provides a limited view of cancer genome structure. Here, we introduce Weaver, an algorithm for the quantification and analysis of allele-specific copy numbers of SVs. Weaver uses a Markov random field to estimate joint probabilities of allele-specific copy numbers of SVs and their inter-connectivity based on paired-end whole-genome sequencing data. Weaver also predicts the timing of SVs relative to chromosome amplifications. We demonstrate the accuracy of Weaver using simulations and findings from whole-genome optical mapping. We apply Weaver to generate allele-specific copy numbers of SVs for MCF-7 and HeLa cell lines and identify recurrent SV patterns in 44 TCGA ovarian cancer whole-genome sequencing datasets. Our approach provides a more complete assessment of the complex genomic architectures inherent to many cancer genomes.

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