Robustness of TRU, Proximal-proliferative (PP), and Proximal-inflammatory (PI) classification. Robustness of TRU, Proximal-proliferative (PP), and Proximal-inflammatory.

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Robustness of TRU, Proximal-proliferative (PP), and Proximal-inflammatory (PI) classification. Robustness of TRU, Proximal-proliferative (PP), and Proximal-inflammatory (PI) classification. A, classification variability due to methodologic alterations or random perturbations of genes or samples. Top, percentage of cases switching GEP when using Spearman correlation instead of Pearson correlation as the similarity metric, or mean gene-centering instead of median gene-centering across all cohorts. For the Shedden et al. (20) cohort the latter analysis was not performed because of reported site-specific expression differences. Center, percentages of cases switching GEP after random selection of different subsets of genes from the 506-gene centroid followed by classification, mimicking the effect of missing data values. Bottom, percentages of cases switching GEP per cohort after random selection of different subsets of cases followed by gene recentering and classification according to the standard approach. Center and bottom, the presented data value for each cohort represents the mean of 20 permutations. B, detailed analysis of the variability in GEP classification caused by proportional changes of a specific GEP in the 230-sample TCGA cohort (14). In a step-by-step process, one TRU-classified tumor (n = 89 originally) was cumulatively removed from the cohort followed by gene recentering and reclassification of the remaining cases. The panel shows how the GEP classification for an individual sample (rows) changes with increasing fractions of originally TRU-classified cases excluded (columns). C, the same analysis as in B is shown, but across all 17 cohorts. Each line corresponds to a unique cohort. Variance is binned in 5% bins (x-axis). A box plot for each bin is superimposed in red. Markus Ringnér et al. Clin Cancer Res 2016;22:218-229 ©2016 by American Association for Cancer Research