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. 2021 Oct 15;12:6023. doi: 10.1038/s41467-021-26299-4

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a The computation pipeline of model construction based on pre-treatment samples in the Riaz et al. cohort. b The volcano plot of differential gene expression analysis between pre-treatment responders (R) and nonresponders (NR) in the Riaz et al. cohort. Log2Fold change (FC) was calculated. The two-sided Wald test was implemented to test if no differential expression between responder and nonresponders. The blue dots represent significantly downregulated (Signif. downregulated) genes (log2Fold Change < −1, P-value < 0.05). The red dots represent significantly upregulated (Signif. upregulated) genes (log2Fold Change > 1, P-value < 0.05). The gray dots represent nonsignificant (NS) genes. c GSEA results of 15 top ranked candidate pathways. Normalized Enrichment Score (NES) and the size of leading-edge geneset are calculated. The permutation based P-value shows the statistical significance of the enrichment score. The number of permutation is 10,000. False discovery rate (FDR) is the estimated probability that the normalized enrichment score represents a false positive finding. d The heatmap of ssGSEA values of pre-treatment responders (R) and nonresponders (NR) in the Riaz et al. cohort. Nonresponders are presented with the number of samples on the left side, and responders are presented with the number of samples on the right side. FDR-corrected two-sided Welch t-test was conducted to compare ssGSEA values between R and NR samples, only FDR < 0.05 showed here. e The boxplot of pre-treatment sample’s Pathway-based super signatures (PASS-PRE) signature score of responders (R) and nonresponders (NR) in the Riaz et al. cohort. The P-value was computed via a one-sided rank-sum test. Boxplot center lines indicate median, box edges represent the interquartile range, whiskers extend to the minimum and maximum, and the outliers are plotted individually using the ‘*’ symbol. f ROC and AUC of PASS-PRE on the pre-treatment samples in the Riaz et al. cohort. g, h The Kaplan–Meier survival analysis of overall survival (OS) (g) and progression-free survival (PFS) (h) of pre-treatment samples in the Riaz et al. cohort. The two-sided log-rank test compared high and low subgroups based on the mean of pre-treatment samples odd ratio as cutoff. Hazard ratio (HR) was calculated and shown with confidence interval (CI). Source data are provided as a Source Data file.