Beata Świątkowska

Supplementary Figure S23 shows heatmap columns that define enriched pathways and rows define signature genes. Enrichment significance is indicated by color intensity. The annotation bar on the top denotes the gene databases used for the enrichment test, and the annotation bar on the right indicates the subtypes of signature genes. Signature genes not associated with any significantly enriched pathway are listed at the bottom of the heatmap.

Supplementary Figure S21 shows (A) Estimation of the minimum gene set per NS-LUAD expression subtype by cross validation in the Sherlock cohort, evaluating 1 to 30 genes per subtype. Box plots show the number of genes per NS-LUAD subtype (x-axis) versus cross-validation error rates (y-axis). (B) Distribution of the error rates for predicting NS-LUAD expression subtypes using the 60-gene signature by cross validation in the Sherlock cohort. Training and testing set error rates are indicated by colors, and median values are marked by dashed lines.

Supplementary Figure S19 shows (A) Comparison of TIDE scores predicting response to ICB across NS-LUAD expression subtypes. B-E, Comparison of (B) predicted cytotoxic T lymphocyte (CTL) levels, (C) tumor mutational burden (TMB), (D) myeloid-derived suppressor cells (MDSC), and (E) cancer associated fibroblast (CAF) abundances across NS-LUAD expression subtypes. Mean values are indicated by the yellow lines. P-values from two-sided Mann-Whitney U-test are shown.

Supplementary Figure S6 shows violin plots that depict the expression levels of (A) the proliferation marker MKI67, and the mesenchymal markers (B) CDH2 and (C) TWIST1 in tumor samples with estimated purity of greater than 0.8. Mean values are indicated by the yellow lines in the violin plots. P-values from two-sided Mann-Whitney U-test are shown in corresponding figures.

Supplementary Figure S4 shows Summary of (A) IPA and (B) GSEA analyses of differentially expressed genes associated with the steady subtype. C-D, Summary of (C) IPA and (D) GSEA analyses of differentially expressed genes associated with the proliferativesubtype. E-F, Summary of (E) IPA and (F) GSEA analyses of differentially expressed genes associated with the chaoticsubtype. In IPA plots, orange and blue indicate positive and negative associations, respectively. In GSEA plots, bar height represents the normalized enrichment score, bar color indicates the FDR-adjusted p-value (FDR <0.1), and pathway annotations are shown on the left.

Supplementary Table S1 s shows summary of RNA-seq-based studies for NS-LUAD.

Supplementary Table S2 shows characteristics and clinical data of patients in the Sherlock cohort.

Supplementary Figure S10 shows proportion of fibroblasts and lepidic components with NS-LUAD expression subtypes are indicated by colors. P-value from Pearson correlation test is shown.