Complex rearrangement detection in cancer genomes using long reads

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Many recent studies highlighted the improved capability of long-read sequencing to detect structural variation in the human genome. For example, these technologies was also recently utilized to produce the first complete assembly of the human genome by the Telomere-to-Telomere consortium. Further, Human Pangenome Reference Consortium has recently released 47 nearly-complete haplotype-resolved human genomes from diverse backgrounds. A few recent studies have utilized long-read sequencing to discover complex genomic changes such as chromothripsis or ecDNA formation. However the broad application of the technology is facing additional hurdles, such as patient sample availability, high-molecular weight DNA extraction, tumor heterogeneity and purity among others. Compared to short-read sequencing, there are little-to-no existing computational approaches to analyze cancer long-read data either. In this project, we aim to capitalize on the recent successes of long-read sequencing for germline variation analyzis, and develop a set of methods for profiling cancer genomes using long reads. This work will open possibilities to detect structural variants and complex rearrangements in cancer genomics with high confidence, study their role in cancer progression and development of drug resistance and potentially discover new actionable mutations and therapeutic targets.