RT Journal Article
SR Electronic
T1 Allele-Specific Quantification of Structural Variations in Cancer Genomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 048207
DO 10.1101/048207
A1 Yang Li
A1 Shiguo Zhou
A1 David C. Schwartz
A1 Jian Ma
YR 2016
UL http://biorxiv.org/content/early/2016/04/12/048207.abstract
AB One of the hallmarks of cancer genome is aneuploidy, resulting in abnormal copy numbers of alleles. Structural variations (SVs) can further modify the aneuploid cancer genomes into a mixture of rearranged genomic segments with extensive range of somatic copy number alterations (CNAs). Indeed, aneuploid cancer genomes have significantly higher rate of CNAs and SVs. However, although methods have been developed to identify SVs and allele-specific copy number of genome (ASCNG) separately, no existing algorithm can simultaneously analyze SVs and ASCNG. Such integrated approach is particularly important to fully understand the complexity of cancer genomes. Here we introduce a new algorithm called Weaver to provide allele-specific quantification of SVs and CNAs in aneuploid cancer genomes. Weaver uses a probabilistic graphical model by utilizing cancer whole genome sequencing data to simultaneously estimate the digital copy number and inter-connectivity of SVs. Our simulation evaluation, comparison with single-molecule Optical Mapping analysis, and real data applications (including MCF-7, HeLa, and TCGA whole genome sequencing samples) demonstrated that Weaver is highly accurate and can greatly refine the analysis of complex cancer genome structure.