Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc
Alice Antonello, Riccardo Bergamin, Nicola Calonaci, Jacob Househam, Salvatore Milite, Marc Williams, Fabio Anselmi, Alberto d’Onofrio, Vasavi Sundaram, Alona Sosinsky, William Cross, Giulio Caravagna
Abstract
Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated using single-cell data and simulations, is applied to over 4000 TCGA and PCAWG samples, and is incorporated into the validation process for the clinically accredited bioinformatics pipeline at Genomics England. CNAqc is designed to support automated quality control procedures for tumor somatic data validation.