CONSERTING: an accurate method for detecting somatic DNA copy number alterations in whole genome sequencing data

Whole genome sequencing (WGS) enables comprehensive identification of DNA copy number alterations (CNAs) in cancer genomes. The recently described phenomenom of “chromothripsis” shows that oscilliating CNAs at multiple genomic loci may arise from a single complex re-arrangement, thereby requiring integration of structural variations (SVs) to fully understand their pathological effect. Here we describe CONSERTING, a novel algorithm for integrative WGS analysis of CNAs and SVs in cancer through iterative analysis of segmentation by read depth change and local SV detection. Analysis of 43 paired tumor/normal WGS cancer datasets from pediatric and adult cancer demonstrated much higher sensitivity and accuracy for CONSERTING than four commonly used somatic CNA detection algorithms or single nucleotide polymorphism arrays. Discovery of a novel oncogenic deletion in NOTCH1 and chromothripsis-like SVs and CNAs in tumor subclones demonstrates the power of this approach in cancer genome analysis.

• Type: Other
• Archiver: European Genome-Phenome Archive (EGA)