Journal
JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 20, Issue 11, Pages 933-944Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2013.0106
Keywords
cancer evolution; genetic variations; tumor phylogeny
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Funding
- NSERC
- STMi-croelectronics Stanford Graduate Fellowship
- Stanford CURIS program
- NIH/NLM
- Bio-X Stanford Interdisciplinary Graduate Fellowship
- KAUST
- Sequencing Initiative of the Stanford Department of Pathology
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Next-generation sequencing technologies provide a powerful tool for studying genome evolution during progression of advanced diseases such as cancer. Although many recent studies have employed new sequencing technologies to detect mutations across multiple, genetically related tumors, current methods do not exploit available phylogenetic information to improve the accuracy of their variant calls. Here, we present a novel algorithm that uses somatic single-nucleotide variations (SNVs) in multiple, related tissue samples as lineage markers for phylogenetic tree reconstruction. Our method then leverages the inferred phylogeny to improve the accuracy of SNV discovery. Experimental analyses demonstrate that our method achieves up to 32% improvement for somatic SNV calling of multiple, related samples over the accuracy of GATK's Unified Genotyper, the state-of-the-art multisample SNV caller.
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