sCNAphase: using haplotype resolved read depth to genotype somatic copy number alterations from low cellularity aneuploid tumors

摘要: Accurate identification of copy number alterations is an essential step in understanding the events driving tumor progression. While a variety algorithms have been developed to use high-throughput sequencing data profile changes, no tool able reliably characterize ploidy and genotype absolute from tumors which contains less than 40% DNA. To increase our power resolve these low cellularity genomes, we novel approach pre-phases heterozygote germline SNPs order replace commonly used 'B-allele frequency' with more powerful 'parental-haplotype frequency'. We also describe 'digital spectral karyotyping' for visualization alterations. apply - sCNAphase loss-of-heterozygosity profiles four publicly available breast cancer cell-lines. Comparisons previous karyotyping microarray studies revealed that identified overall individual changes each cell-line. Analysis tumor-normal cell-line mixtures demonstrated capacity this method determine level purity as little 5% DNA consistently identify sCNAs samples at 10% purity. This methodology has potential bring sCNA profiling low-cellularity tumors, form unable be profiled by current methods.