CNAViz: An interactive webtool for user-guided segmentation of tumor DNA sequencing data

Abstract

Copy-number aberrations (CNAs) are genetic alterations that amplify or delete the number of copies of large genomic segments. Although they are ubiquitous in cancer and, thus, a critical area of current cancer research, CNA identification from DNA sequencing data is challenging because it requires partitioning of the genome into complex segments with the same copy-number states that may not be contiguous. Existing segmentation algorithms address these challenges either by leveraging the local information among neighboring genomic regions, or by globally grouping genomic regions that are affected by similar CNAs across the entire genome. However, both approaches have limitations: overclustering in the case of local segmentation, or the omission of clusters corresponding to focal CNAs in the case of global segmentation. Importantly, inaccurate segmentation will lead to inaccurate identification of important CNAs. For this reason, most pan-cancer research studies rely on manual procedures of quality control and anomaly correction. To improve copy-number segmentation and their control, we introduce CNAVO_SCPLOWIZC_SCPLOW, a web-based tool that enables the user to simultaneously perform local and global segmentation, thus overcoming the limitations of each approach. Using simulated data, we demonstrate that by several metrics, CNAVO_SCPLOWIZC_SCPLOW allows the user to obtain more accurate segmentation relative to existing local and global segmentation methods. Moreover, we analyze six bulk DNA sequencing samples from three breast cancer patients. By validating with parallel singlecell DNA sequencing data from the same samples, we show that by using CNAVO_SCPLOWIZC_SCPLOW, our user was able to obtain more accurate segmentation and improved accuracy in downstream copy-number calling. CNAVO_SCPLOWIZC_SCPLOW is available at https://github.com/elkebir-group/cnaviz.