Format

Send to

Choose Destination
Cell Syst. 2016 Jul;3(1):21-34. doi: 10.1016/j.cels.2016.05.007. Epub 2016 Jul 21.

Allele-Specific Quantification of Structural Variations in Cancer Genomes.

Author information

1
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
2
Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
3
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.

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.

PMID:
27453446
PMCID:
PMC4965314
DOI:
10.1016/j.cels.2016.05.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center