Prioritization of CIS genes that are candidate mechanistic determinants of NEPC
| Gene | Name | Function | Total # of tumors with CIS | % of tumors with CIS (by phenotype) | CIS FDR | DGE logFC | DGE FDR | VIPER FDR | CINDy FDR | Fisher’s P value | VIPER score | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NEPC | Non-NEPC | |||||||||||
| Ezh2 | Enhancer of zeste homolog 2 | Histone methyltransferase | 16 | 38% | 62% | 5.15E-19 | 1.363 | 2.57E-06 | 5.34E-28 | 2.225E-308 | 5.00E-48 | 10.907 |
| Sirt1 | Sirtuin 1 | NAD-dependent deacetylase | 6 | 67% | 33% | 3.41E-08 | 0.834 | 1.07E-04 | 4.20E-18 | 6.434E-140 | 3.47E-26 | 8.594 |
| Arid1a | AT-Rich Interaction Domain 1A | Chromatin remodeler | 8 | 50% | 50% | 6.68E-14 | 0.747 | 5.80E-05 | 1.40E-12 | 2.225E-308 | 1.27E-26 | 6.987 |
| Aifm3 | Apoptosis Inducing Factor Mitochondria Associated 3 | Apoptotic regulator, mitochondria | 8 | 38% | 62% | 8.51E-14 | 3.733 | 7.40E-06 | 5.78E-11 | 2.225E-308 | 8.04E-26 | 6.445 |
| Rad21 | Double-Strand-Break Repair Protein Rad21 Homolog | DNA repair | 8 | 17% | 83% | 1.21E-10 | 0.697 | 4.56E-04 | 5.93E-10 | 5.055E-124 | 4.57E-20 | 6.082 |
| Msi2 | Musashi RNA Binding protein 2 | Cell cycle regulation | 10 | 80% | 20% | 1.56E-12 | 1.727 | 7.71E-06 | 1.76E-09 | 1.3778E-80 | 3.84E-23 | 5.905 |
| Cxxc5 | CXXC Finger Protein 5 | DNA damage, WNT signaling | 15 | 47% | 53% | 6.81E-14 | 0.860 | 5.35E-04 | 9.90E-02 | 2.225E-308 | 3.06E-15 | 1.287 |
| Golph3 | Golgi Phosphoprotein 3 | Golgi trafficking | 11 | 36% | 64% | 2.29E-04 | −0.520 | 7.31E-04 | 9.56E-02 | 2.340E-304 | 2.89E-06 | −1.307 |
| Gdi2 | GDP Dissociation Inhibitor 2 | Vesicular trafficking | 8 | 25% | 75% | 4.96E-11 | −0.627 | 1.27E-05 | 6.76E-07 | 2.225E-308 | 5.38E-19 | −4.832 |
| Prkci | Protein Kinase C Iota | Cytoskeleton, cell migration | 8 | 25% | 75% | 7.38E-06 | −0.813 | 1.84E-04 | 1.63E-07 | 2.225E-308 | 1.52E-13 | −5.108 |
| Nisch | Nischarin | Cell migration | 13 | 31% | 69% | 6.95E-13 | −0.632 | 4.49E-04 | 3.83E-10 | 2.225E-308 | 2.03E-22 | −6.152 |
| Spred1 | Sprouty Related EVH1 Domain Containing 1 | Activation of MAPK | 7 | 29% | 71% | 4.49E-05 | −2.043 | 3.75E-07 | 4.57E-27 | 2.225E-308 | 2.88E-34 | −10.710 |
| Tgfbr2 | Transforming Growth Factor Beta Receptor 2 | Cell proliferation | 7 | 29% | 71% | 8.99E-13 | −2.219 | 4.64E-05 | 4.19E-27 | 3.610E-249 | 8.65E-40 | −10.718 |
| Ppp2r2a | Protein Phosphatase 2 Regulatory Subunit B alpha | Cell growth and division | 9 | 11% | 89% | 4.53E-14 | −1.233 | 1.78E-06 | 3.84E-27 | 2.225E-308 | 1.73E-42 | −10.726 |
| Evi2a | Ecotropic Viral Integration Site 2A | Cell surface receptor | 19 | 11% | 89% | 1.99E-42 | −2.250 | 1.89E-04 | 1.09E-38 | 2.225E-308 | 7.63E-80 | −12.956 |
| Gene | Name | Function | Total # of tumors with CIS | % of tumors with CIS (by phenotype) | CIS FDR | DGE logFC | DGE FDR | VIPER FDR | CINDy FDR | Fisher’s P value | VIPER score | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NEPC | Non-NEPC | |||||||||||
| Histone methyltransferase | 16 | 38% | 62% | 5.15E-19 | 1.363 | 2.57E-06 | 5.34E-28 | 2.225E-308 | 5.00E-48 | 10.907 | ||
| NAD-dependent deacetylase | 6 | 67% | 33% | 3.41E-08 | 0.834 | 1.07E-04 | 4.20E-18 | 6.434E-140 | 3.47E-26 | 8.594 | ||
| Chromatin remodeler | 8 | 50% | 50% | 6.68E-14 | 0.747 | 5.80E-05 | 1.40E-12 | 2.225E-308 | 1.27E-26 | 6.987 | ||
| Apoptotic regulator, mitochondria | 8 | 38% | 62% | 8.51E-14 | 3.733 | 7.40E-06 | 5.78E-11 | 2.225E-308 | 8.04E-26 | 6.445 | ||
| DNA repair | 8 | 17% | 83% | 1.21E-10 | 0.697 | 4.56E-04 | 5.93E-10 | 5.055E-124 | 4.57E-20 | 6.082 | ||
| Cell cycle regulation | 10 | 80% | 20% | 1.56E-12 | 1.727 | 7.71E-06 | 1.76E-09 | 1.3778E-80 | 3.84E-23 | 5.905 | ||
| DNA damage, WNT signaling | 15 | 47% | 53% | 6.81E-14 | 0.860 | 5.35E-04 | 9.90E-02 | 2.225E-308 | 3.06E-15 | 1.287 | ||
| Golgi trafficking | 11 | 36% | 64% | 2.29E-04 | −0.520 | 7.31E-04 | 9.56E-02 | 2.340E-304 | 2.89E-06 | −1.307 | ||
| Vesicular trafficking | 8 | 25% | 75% | 4.96E-11 | −0.627 | 1.27E-05 | 6.76E-07 | 2.225E-308 | 5.38E-19 | −4.832 | ||
| Cytoskeleton, cell migration | 8 | 25% | 75% | 7.38E-06 | −0.813 | 1.84E-04 | 1.63E-07 | 2.225E-308 | 1.52E-13 | −5.108 | ||
| Cell migration | 13 | 31% | 69% | 6.95E-13 | −0.632 | 4.49E-04 | 3.83E-10 | 2.225E-308 | 2.03E-22 | −6.152 | ||
| Activation of MAPK | 7 | 29% | 71% | 4.49E-05 | −2.043 | 3.75E-07 | 4.57E-27 | 2.225E-308 | 2.88E-34 | −10.710 | ||
| Cell proliferation | 7 | 29% | 71% | 8.99E-13 | −2.219 | 4.64E-05 | 4.19E-27 | 3.610E-249 | 8.65E-40 | −10.718 | ||
| Cell growth and division | 9 | 11% | 89% | 4.53E-14 | −1.233 | 1.78E-06 | 3.84E-27 | 2.225E-308 | 1.73E-42 | −10.726 | ||
| Cell surface receptor | 19 | 11% | 89% | 1.99E-42 | −2.250 | 1.89E-04 | 1.09E-38 | 2.225E-308 | 7.63E-80 | −12.956 | ||
CIS FDR: adjusted P value using false discovery rate for each common-insertion site from TAPDANCE analysis. DGE logFC: logFold-change between NEPC versus non-NEPC tumors from differential gene expression analysis. DGE FDR: adjusted P value using false discovery rate for differential gene expression between NEPC versus non-NEPC tumors. VIPER FDR: adjusted P value using false discovery rate for MRs from VIPER analysis. CINDy FDR: adjusted P value using false discovery rate for each candidate modulator gene from CINDy analysis. VIPER score: VIPER score from differential protein activity analysis between NEPC versus non-NEPC tumors.