title: Allele-Specific Quantification of Structural Variations in Cancer Genomes.
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.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Shiguo
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Schwartz
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address: jianma@cs.cmu.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
mesh_terms: D000465:Algorithms; D000483:Alleles; D056915:DNA Copy Number Variations; D056914:Genomic Structural Variation; D023281:Genomics; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009369:Neoplasms; D017422:Sequence Analysis, DNA