Fig. 2: SHAP analysis of gene-gene interactions in immune response prediction.

a 20 Top genes with highest absolute Shapley score identified in the model. b SHAP value summary plot depicting the impact of each of the most important genes on model output. Gene expression (shown by coloring) as a function of SHAP value (x-axis) showing the relation between expression pattern and model’s prediction. c Scatter plots showing the relationship between gene expression and SHAP values for key genes (GAPDH, STAT1, IFITM2, and HSPA1A). d Interaction plots illustrating the SHAP value dependencies between specific gene pairs: GAPDH & STAT1 (left), CD38 & CCL5 (middle), CCR7 & HLA-B (right). Expression of the first gene shown as x-axis position, and the expression of the interacting gene shown as coloring; SHAP value shown as y-axis position. Decision trees beneath the plots show the simplified relation of the gene-pairs conditional expression with response to ICI. e Interaction plots comparing SHAP value dependencies between gene pairs trained on all cells vs T cells: CCL5 & CD38 (left), CCL4 & HLA-B (right). Expression of the first gene shown as x-axis position, and the expression of the interacting gene shown as coloring; SHAP value shown as y-axis position. f Waterfall plots showing SHAP value contributions to individual model predictions (sample prediction). Four examples of patients predicted as responders or non-responders, with differences in gene expression patterns contributing to the outcome predictions. Pre_P35 – Responder predicted correctly, Pre_P2 – Non-Responder predicted correctly, Pre_P28 – Responder predicted as Non-Responder, Pre_P3 – Non-Responder predicted as Responder.