Seminar — Dr Hao Chen — Allele-specific copy number profiling by next-generation DNA sequencing
Starts: 9:00 am
Ends: February 20, 2015 - 10:00 am
Location: GBSF Room 4202
Description: Part of the Genome Center Structural and Functional Genomics Seminar Series
The progression and clonal development of tumors often involve amplifications and deletions 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 giving a more complete portrait of tumor genomes and the inference of their clonal history. We propose a novel method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normal. Falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. We applied this method in 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 allow us to draw detailed conclusions regarding the clonal history of the individual’s colon cancer.