geneshot: gene-level metagenomics identifies genome islands associated with immunotherapy response

Genome Biol. 2021 May 5;22(1):135. doi: 10.1186/s13059-021-02355-6.

Abstract

Researchers must be able to generate experimentally testable hypotheses from sequencing-based observational microbiome experiments to discover the mechanisms underlying the influence of gut microbes on human health. We describe geneshot, a novel bioinformatics tool for identifying testable hypotheses based on gene-level metagenomic analysis of WGS microbiome data. By applying geneshot to two independent previously published cohorts, we identify microbial genomic islands consistently associated with response to immune checkpoint inhibitor (ICI)-based cancer treatment in culturable type strains. The identified genomic islands are within operons involved in type II secretion, TonB-dependent transport, and bacteriophage growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genomic Islands / genetics*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy*
  • Metagenomics*
  • Microbiota / genetics
  • Software*
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors

Associated data

  • figshare/10.6084/m9.figshare.14417120
  • figshare/10.6084/m9.figshare.14417222.v1