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 with original TCGA samples. "Mixed-evidence"species can be further distinguished by gene copy and nucleotide variants. 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 discovery of prognostic species and blood signatures of mucosal barrier injuries and enabled systematic matched microbe-host multi-omics analyses which will help guide future studies of the microbiome's role in human health and disease.
