Performance analysis of MIL models
(A and B) MIL models perform better than percentage tumor nuclei estimates and successfully classify samples into tumor versus normal. (A) Spearman's correlation coefficient versus mean-absolute-error plot is given for MIL models' tumor purity predictions (represented by triangles) and pathologists' percentage tumor nuclei estimates (represented by circles) in the test sets of different cohorts (showed in different colors). MIL models' predictions achieve lower mean absolute error and higher Spearman's correlation coefficient than percentage tumor nuclei estimates. See also Tables S3 and S5. (B) ROC curve analysis over MIL models' predictions for tumor versus normal sample classification. The area under curve values with 95% CIs are given in the legend. MIL models successfully classified samples into tumor versus normal in all cohorts.
(C and D) The top and bottom slides of a tumor sample are different in tumor purity. In the test set of each cohort, for a tumor sample having top and bottom slides, we conducted two experiments. (C) The trained MIL model's predictions from the top and bottom slides of a sample are statistically compared using Wilcoxon signed-rank test.53 Each box plot summarizes the p values obtained in a cohort. For at least 95% of the samples in each cohort, the top and bottom slides are significantly different (p < 0.05) in tumor purity. The dashed line shows p = 0.05. See also Table S6. (D) For each sample, the absolute error between genomic tumor purity value and the MIL model's prediction using both slides and the expected value of absolute errors between genomic tumor purity value and the MIL model's predictions over individual slides are calculated. Box plots summarize the absolute errors in two approaches. They are statistically compared using Wilcoxon signed-rank test,53 and the results are presented on top of the plots such that p > 0.05 (ns, not significant), ∗p ≤ 0.05, ∗∗p ≤ 0.01, and ∗∗∗p ≤ 0.001. See also Table S7. Whiskers show 5th and 95th percentiles, and red lines show median values. n, number of tumor samples with two slides.