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1 Supplementary Information Gene co-expression network analysis reveals common system-level prognostic genes across cancer types properties of Supplementary Figure 1 The robustness and overlap of prognostic mrna genes in different cancer types (A) The distributions of the proportion of prognostic mrna genes showing significant expression-survival correlations in 100 randomly sampled subsets (75% of the original sample size) in GBM, OV, BRCA and KIRC. The grey lines mark the average proportion across the 100 sample subsets. (B) The Venn diagram of prognostic mrna genes acrosss the four cancer types.
2 Supplementary Figure 2 The relationships of the proportion of prognostic mrna genes and connectivity in the co-expression networks For each cancer type, the proportion curve of prognostic mrnas in different connectivity bins is shown in a solid line; and the average proportion of prognostic mrnas is shown in a dotted line.
3 Supplementary Figure 3 Comparison of prognostic mrnas with a randomly selected same-size set of non-prognostipseudo-prognostic genes for each mrnas in terms of hub depletion (A) For comparison, a randomly selected same-size set of non-prognostic mrnas was chosen as cancer type; and (B) based on true prognostic mrna genes. In (A) and (B), solid bars represent the proportions of hub genes among (pseudo-)prognostic mrna genes; striped bars represent the proportions of hub genes among non-prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-valuess were calculated based on Fisher s exact tests.
4 Supplementary Figure 4 The depletion of prognostic mrna genes in the hubs (top 5%) The 5% of nodes with the highest connectivity were defined as hubs. Solid bars represent the proportions of hub genes among prognostic mrna genes; striped bars represent the proportions of hub genes among non-prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
5 Supplementary Figure 5 Hub depletion and module enrichment of prognostic mrnas (top 1000 prognostic mrnas) (A) The P-value distributions of the correlations of mrna expression with overall survival based on the univariate Cox model in the four cancer types. The top prognostic mrna genes were identified. (B) and (C) Prognostic mrna genes are depletedd in the hubs. The 1% and 5% of nodes with the highest connectivity were defined as hubs, respectively. Solid bars represent the proportions of hub genes among prognostic mrna genes; striped bars represent the proportions of hub genes among non-prognostic mrna genes. (D) Prognostic genes are enriched in the modules. Solid bars represent the proportions of module genes among prognostic mrna genes; striped bars represent the proportions of module genes among non-prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
6 Supplementary Figure 6 Comparison of prognostic mrnas with a randomly selected same-size set of non-prognostipseudo-prognostic genes for each mrnas in terms of module enrichment (A) For comparison, a randomly selected same-size set of non-prognostic mrnas was chosen as cancer type; and (B) based on true prognostic mrna genes. In (A) and (B), solid bars represent the proportions of hub genes among (pseudo-)prognostic mrna genes; striped bars represent the proportions of hub genes among non-prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-valuess were calculated based on Fisher s exact tests.
7 Supplementary Figure 7 Target genes of prognostic mirna genes are depleted in the hubs (top 5%) The 5% of nodes with the highest connectivity were defined as hubs. Solid bars represent the proportions of hub genes among target genes of prognostic mirnas; striped bars represent the proportions of hub genes among non-target genes of prognostic mirnas. Errorr bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
8 Supplementary Figure 8 Different sets of target genes of prognostic mirna genes are depletedd in the hubs The 1% of nodes with the highest connectivity were defined as hubs. Solid bars represent the proportions of hub genes among target genes of prognostic mirnas; striped bars represent the proportions of hub genes among non-target genes of prognostic mirnas. Target genes weree defined with different criteria: (A) target genes of two prognostic mirnas, (B) target genes of three prognostic mirnas, and (C) target genes of four prognostic mirnas. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
9 Supplementary Figure 9 Hub depletion and module enrichment of prognostic mirnas target genes (top 50 prognostic mirnas) (A) The P-value distributions of the correlations of mirna expression with overall survival based on the univariate Cox model in the four cancer types. The top 50 prognostic mirna genes were identified. (B) and (C) Target genes of prognostic mirna genes are depleted in the hubs. The 1% and 5% of nodes with the highest connectivity were defined as hubs, respectively. Solid bars represent the proportions of hub genes among target genes of prognostic mirnas; striped bars represent the proportions of hub genes among non-target genes of prognostic mirnas. (D) Target genes of prognostic mirnas are enriched in the modules. Solid bars represent the proportions of target-module enriched mirnas among prognostic mirnas; striped bars represent the proportions of target-module enriched mirnas among non-prognostic mirnas. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
10 Supplementary Figure 10 Clinical relevance of sample clusters based on the gene expression of prognostic modules For each cancer type, the left panel is NMF clusters, and the right panel is the Kaplan-Meier plot showing the P value of the log-rank test.
11 Supplementary Figure 11 Identification of prognostic mrna genes The P-value distributions of the correlations of mrna expression with overall survival based on the univariate Cox model in different cancer types. Based on the signal-to-noise ratio, the profiling platforms for identifying prognostic mrna genes were boxed.
12 Supplementary Figure 12 The connectivity distributionss of gene co-expression networks The top 1% or 5% cutoff well covers the highly connected nodes in the power-law tail.
13 Figure S13 The depletion of prognostic mrna genes in the hubs defined by the adjacency connectivity The 1% and 5% of nodes with the highest connectivity were defined as hubs (A) and (B), respectively. Solid bars represent the proportions of hub genes among prognostic mrna genes; striped bars represent the proportions of hub genes among non-prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
14 Supplementary Figure 14 Module enrichment of prognostic mrnas Module genes were defined with a more sensitive parameter (the SplitDepth value = 4) in WGCNA. Solid bars represent the proportions of module genes among prognostic mrna genes; striped bars represent the proportions of module genes among non- prognostic mrna genes. Error bars indicate ± 1 s.e.m., and P-values were calculated based on Fisher s exact tests.
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Type of file: PDF Size of file: 0 KB Title of file for HTML: Supplementary Information Description: Supplementary Figures
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