Segmentum: a tool for copy number analysis of cancer genomes

Ebrahim Afyounian, Matti Annala, Matti Nykter

Somatic alterations, including loss of heterozygosity, can affect the expression of oncogenes and tumor suppressor genes. Whole genome sequencing enables detailed characterization of such aberrations. However, due to the limitations of current high throughput sequencing technologies, this task remains challenging. Hence, accurate and reliable detection of such events is crucial for the identification of cancer-related alterations. We introduce a new tool called Segmentum for determining somatic copy numbers using whole genome sequencing from paired tumor/normal samples. In our approach, read depth and B-allele fraction signals are smoothed, and double sliding windows are used to detect breakpoints, which makes our approach fast and straightforward. Because the breakpoint detection is performed simultaneously at different scales, it allows accurate detection as suggested by the evaluation results from simulated and real data. We applied Segmentum to paired tumor/normal whole genome sequencing samples from 38 patients with low-grade glioma from the TCGA dataset and were able to confirm the recurrence of copy-neutral loss of heterozygosity in chromosome 17p in low-grade astrocytoma characterized by IDH1/2 mutation and lack of 1p/19q co-deletion, which was previously reported using SNP array data. Segmentum is an accurate, user-friendly tool for somatic copy number analysis of tumor samples. We demonstrate that this tool is suitable for the analysis of large cohorts, such as the TCGA dataset.