Abstract 5117: Comprehensive structural analysis of cancer genomes by genome mapping

Abstract

Abstract Tumors are often comprised of heterogeneous populations of cells, with certain cancer-driving mutations at low allele fractions in early stages of cancer development. Effective detection of such variants is critical for diagnosis and targeted treatment. However, typical short sequence reads are limited in their ability to span across repetitive regions of the genome and to facilitate structural variant (SV) analysis. Based on specific labeling and mapping of ultra-high molecular weight (UHMW) DNA, we developed a single-molecule platform that has the potential to detect disease-relevant SVs and give a high-resolution view of tumor heterogeneity. We developed a DNA isolation and sample preparation workflow that preserves the DNA integrity and conserves structural variation information from blood, cells and preserved tissue. Single molecules are labeled at specific motifs and analyzed in massively parallel nanochannels. The single-molecule maps are used in a bioinformatics pipeline that effectively detects structural variants at low allele fractions. It includes single-molecule based SV calling and fractional copy number analysis. Preliminary analyses using simulated and well-characterized cancer samples showed high sensitivity for variants of different types at as low as 5% allele fractions. The candidate variants are then annotated and further prioritized based on control data and publicly available annotations. The data are imported into a graphical user interface tool that includes new visualization tools (such as Circos diagrams) for real-time interactive visualization and curation. Bionano offers sample preparation, DNA imaging and genomic data analysis technologies combined into one streamlined workflow that enables high-throughput genome mapping on the Bionano Saphyr system. Together, these components allows for efficient analysis of any genome of interest. Citation Format: Ernest Lam, Yannick Delpu. Comprehensive structural analysis of cancer genomes by genome mapping [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5117.