RT Journal Article
SR Electronic
T1 Gastric cancer genomics study using reference human pangenomes
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402977
DO 10.26508/lsa.202402977
VO 8
IS 4
A1 Jiao, Du
A1 Dong, Xiaorui
A1 Fan, Shiyu
A1 Liu, Xinyi
A1 Yu, Yingyan
A1 Wei, Chaochun
YR 2025
UL http://www.life-science-alliance.org/content/8/4/e202402977.abstract
AB 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.The sequencing data in this article have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation (GSA-Human), HRA002344 for normal gastric mucosa and HRA002333 for gastric cancer. The codes and somatic structural variants for this study are available at dudududu12138/GGCPan (github.com).