Cancer can be generally defined as a cluster of systematic diseases triggered by abnormal cell proliferation and growth. With the development of biological sciences and biotechnologies, the etiology of cancer is partially revealed, including some of the most substantial pathogenic factors (either endogenous [genetics] or exogenous [environmental]). However, some remaining factors that contribute to the tumorigenesis but have not been analyzed and discussed in detail remain. For instance, some typical correlations between microorganisms and tumorigenesis have been reported already, but previous studies are just sporadic studies on single microorganism–cancer subtype pairs and do not explain and validate the specific contribution of microbiome on tumorigenesis. On the basis of the systematic microbiome analyses of blood and cancer-associated tissues in cancer patients/controls in public domain, we performed interpretable analyses. We identified several core regulatory microorganisms that contribute to the classification of multiple tumor subtypes and established quantitative predictive models for interpretable prediction by using multiple machine learning methods. We also compared the optimal features (microorganisms) and rules identified from microbiome profiles processed using the Kraken and the SHOGUN. Collectively, our study identified new microbiome signatures and their interpretable classification rules for cancer discrimination and carried out reliable methodological comparison for robust cancer microbiome analyses, thereby promoting the development of tumor etiology at the microbiome level.
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