The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants

Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types from The Cancer Genome Atlas (TCGA), revealing that species equiprevalent across sample types are predominantly contaminants, bearing unique signatures from each TCGA-designated sequencing center. Removing such species mitigated batch effects and isolated the tissue-resident microbiome, which was validated by original matched TCGA samples. Gene copies and nucleotide variants can further distinguish mixed-evidence species. We, thus, present The Cancer Microbiome Atlas (TCMA), a collection of curated, decontaminated microbial compositions of oropharyngeal, esophageal, gastrointestinal, and colorectal tissues. This led to the discovery of prognostic species and blood signatures of mucosal barrier injuries and enabled systematic matched microbe-host multi-omic analyses, which will help guide future studies of the microbiome’s role in human health and disease. [Display omitted] •Decontaminated microbial compositions for 3,689 gastrointestinal cancer samples•Resolved “mixed-evidence” species with gene and nucleotide resolution•Identified prognostic species and blood signatures of mucosal barrier injury•Enabled matched multi-omic, pan-cancer analyses of host-microbe interactions Dohlman et al. present The Cancer Microbiome Atlas, a public database of decontaminated, tissue-resident microbial profiles of TCGA gastrointestinal cancer tissues. As these profiles are matched to specific TCGA tissue samples, this work allows identification of prognostic species and provides a resource for performing multi-omic, pan-cancer analyses of host-microbe interactions.