RT Journal Article SR Electronic(1) A1 Tan, Cedric Chih Shen A1 Acman, Mislav A1 van Dorp, Lucy A1 Balloux, FrancoisYR 2021 T1 Metagenomic evidence for a polymicrobial signature of sepsis JF Microbial Genomics, VO 7 IS 9 OP SP 000642 DO https://doi.org/10.1099/mgen.0.000642 PB Microbiology Society, SN 2057-5858, AB Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterize the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera [area under the receiver operating characteristic (AUROC=0.995)], including after removal of species ‘culture-confirmed’ as the cause of sepsis through clinical testing (AUROC=0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls. While prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis, and ultimately support the development of clinical diagnostic or even prognostic tools., UL https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000642