FACETS: Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing

Abstract

Clinical sequencing studies routinely involve molecular profiling of patients for mutations and copy number alterations. However, detection of "actionable" aberrations to guide treatment decisions require accurate, tumor purity-, ploidy-, and clonal heterogeneity-adjusted integer copy number calls. In this chapter, we describe the FACETS algorithm, an Allele-Specific Copy Number (ASCN) analysis tool with a broad application to whole-genome, whole-exome, as well as targeted panel sequencing platforms to annotate the genome for the detection of copy number alterations including homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH) events, allele-specific gains/amplifications, and cellular fraction profiles.We will describe some methodological details on joint segmentation of total and allele-specific copy number, on the estimation of integer copy number calls adjusting for tumor purity, ploidy, and intratumor heterogeneity, along with comprehensive output and integrated visualization. We also provide a tutorial on the installation, application, and tips to run and interpret FACETS.

Keywords: Allele-specific copy number analysis; High-throughput DNA sequencing; Integer copy number; Ploidy; Purity.