Gastric cancer genomics study using reference human pangenomes.

Abstract

A pangenome is the sum of the genetic information of all individuals in a species or a population. Genomics research has been gradually shifted to a paradigm using a pangenome as the reference. However, in disease genomics study, pangenome-based analysis is still in its infancy. In this study, we introduced a graph-based pangenome GGCPan from 185 patients with gastric cancer. We then systematically compared the cancer genomics study results using GGCPan, a linear pangenome GCPan, and the human reference genome as the reference. For small variant detection and microsatellite instability status identification, there is little difference in using three different genomes. Using GGCPan as the reference had a significant advantage in structural variant identification. A total of 24 candidate gastric cancer driver genes were detected using three different reference genomes, of which eight were common and five were detected only based on pangenomes. Our results showed that disease-specific pangenome as a reference is promising and a whole set of tools are still to be developed or improved for disease genomics study in the pangenome era.