Biostatistics Seminar: Hao Chen
DATE: Tuesday, May 27th, 2014
TIME: 4:10pm (refreshments at 3:30pm, MSB 4110)
LOCATION: Mathematical Sciences Building 1143 (note location change)
SPEAKER: Hao Chen, Dept of Statistics, UC Davis
TITLE: Allele-specific copy number profiling by next-generation DNA sequencing
ABSTRACT: The progression and clonal development of tumors often involve gains and losses of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals. Falcon is based on a change-point model on a bivariate mixed Binomial processes, which explicitly models the copy numbers of the two homologous chromosomes and corrects for local allele-specific coverage biases in the tumor sample by conditioning on a matched control sample. By using the Binomial rather than the normal distribution, falcon correctly pools evidence from sites with low coverage. A modified Bayesian information criterion (mBIC) is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in-silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer.