Extended Data Fig. 2: Sensitivity analyses of gut microbial strain-efficacy classifiers.

a, Comparison of the RvsP and PFS12 binary endpoints. Venn diagrams show the overlap between the ‘negative and ‘positive’ outcome populations (P/non-PFS12 and R/PFS12 respectively). Size of circles (area) in proportion to population size, with set differences labelled. b, AUC scores for the best iteration of PFS12 classifiers for each feature-set combination during 20-repeated 5-fold cross-validation (100 folds each): clinical (yellow), microbiome (blue) and combined (green), at different taxonomic resolutions. Mean (circle) and standard deviation (error bars) over the 100 folds. Linear model line-of-best-fit for AUC score and taxonomic rank of microbiome-only feature sets (with shaded 95% confidence interval) superimposed. Kendall τ and p-value for association between AUC score and taxonomic rank of microbiome-only feature sets printed. Mann-Whitney U p-value for comparison of AUCs of specific pairwise feature-sets (depicted by callipers) printed. c, Patient’s predicted RvsP (using strain-RvsP RF classifiers trained on the full evaluable cohort) vs. actual BOR outcome (cPD n = 21, PD n = 30, SD n = 29, PR n = 22, CR n = 4). Boxplot centre line= median; box limits= upper and lower quartiles; whiskers= 1.5x interquartile range. Kendall rank correlation τ and p-value for association between predicted RvsP and actual BOR printed. d, Kaplan-Meier overall survival curves for those patients with a best overall response (BOR) of stable disease (n = 29), stratified by those with above median (blue) and below median (red) strain-RvsP RF classifier predictions. Bottom panel shows number of patients at risk at each marked interval. P-value by log-rank test printed. Acronyms: P= progressors (RECIST progressive disease (PD) or clinical progressive disease (cPD)), R= responders (RECIST complete response (CR) or partial response (PR)), GYN= gynaecological, NEN= neuro-endocrine neoplasm, UGB= upper gastrointestinal & biliary, ROC= receiver operating characteristic, AUC= area under curve, OS= overall survival, SD= stable disease, RvsP= response versus progression, cPD= clinical progressive disease, PD= progressive disease, SD= stable disease, PR= partial response, CR = complete response.