Table 5. Molecular pathways and associated proteins revealed by CIS subgroup analysis.
| MSs-CIS | |||||
|---|---|---|---|---|---|
| KEGG ID | KEGG Term | Term P values Corr Bonf | Times Found | Pathway Associated Genes Found in Subnetworks | Pathway Associated Genes Not Found in Subnetworks |
| KEGG:04930 | Type II diabetes mellitus | 7,73E-07 | 1 | IRS4, MAPK1, IRS2, INSR, PIK3R1, PIK3R2 | ABCC8, ADIPOQ, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, GCK, HK1, HK2, HK3, HKDC1, IKBKB, INS, IRS1, KCNJ11, MAFA, MAPK10, MAPK3, MAPK8, MAPK9, MTOR, PDX1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R3, PIK3R5, PKLR, PKM2, PRKCD, PRKCE, PRKCZ, SLC2A2, SLC2A4, SOCS1, SOCS2, SOCS3, SOCS4, TNF |
| KEGG:04614 | Renin-angiotensin system | 6,88E-06 | 4 | AGT, MAS1 | ACE, ACE2, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MME, NLN, REN, THOP1 |
| KEGG:04330 | Notch signaling pathway | 3,89E-10 | 1 | NOTCH3, NCSTN, NOTCH2, APH1A, RBPJ | ADAM17, CIR1, CREBBP, CTBP1, CTBP2, DLL1, DLL3, DLL4, DTX1, DTX2, DTX3, DTX3L, DTX4, DVL1, DVL2, DVL3, EP300, HDAC1, HDAC2, HES1, HES5, JAG1, JAG2, KAT2A, KAT2B, LFNG, MAML1, MAML2, MAML3, MFNG, NCOR2, NOTCH1, NOTCH4, NUMB, NUMBL, PSEN1, PSEN2, PSENEN, PTCRA, RBPJL, RFNG, SNW1 |
| KEGG:04610 | Complement and coagulation cascades | 1,05E-08 | 1 | KNG1, C7, A2M, SERPINE1, SERPING1, SERPINA1, PLG | BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PROC, PROS1, SERPINA5, SERPINC1, SERPIND1, SERPINF2, TFPI, THBD, VWF |
| KEGG:04960 | Aldosterone-regulated sodium reabsorption | 1,78E-04 | 1 | MAPK1, INSR, PIK3R1, PIK3R2 | ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP1B4, FXYD2, FXYD4, HSD11B2, IGF1, INS, IRS1, KCNJ1, KRAS, MAPK3, NEDD4L, NR3C2, PDPK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R3, PIK3R5, PRKCA, PRKCB, PRKCG, SCNN1A, SCNN1B, SCNN1G, SFN, SGK1, SLC9A3R2 |
| SA-MS | |||||
| KEGG:04621 | NOD-like receptor signaling pathway | 6,69E-08 | 1 | HSP90AA1, RELA, NFKBIA, TRAF6, TNFAIP3, IKBKB | BIRC2, BIRC3, CARD18, CARD6, CARD8, CARD9, CASP1, CASP5, CASP8, CCL2, CCL5, CHUK, CXCL1, CXCL2, ERBB2IP, HSP90AB1, HSP90B1, IKBKG, IL18, IL1B, IL6, IL8, MAP3K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MEFV, NAIP, NFKB1, NFKBIB, NLRC4, NLRP1, NLRP3, NOD1, NOD2, PSTPIP1, PYCARD, PYDC1, RIPK2, SUGT1, TAB1, TAB2, TAB3, TNF, TRIP6 |
| KEGG:04614 | Renin-angiotensin system | 6,88E-09 | 7 | AGT, MAS1 | ACE, ACE2, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MME, NLN, REN, THOP1 |
| KEGG:04610 | Complement and coagulation cascades | 7,89E-02 | 2 | A2M, THBD, F5, F2, SERPING1, SERPINA1, F7, PROC | BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2R, F3, F8, F9, FGA, FGB, FGG, KLKB1, KNG1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PLG, PROS1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, TFPI, VWF |
| CDMS | |||||
| KEGG:04610 | Complement and coagulation cascades | 3,80E-07 | 1 | KNG1, F12, A2M, F2, SERPING1, SERPINA1, PLG | BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F13A1, F13B, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PROC, PROS1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, TFPI, THBD, VWF |
| KEGG:05130 | Pathogenic Escherichia coli infection | 1,61E-10 | 1 | PRKCA, ARPC3, FYN, ABL1, NCL, ITGB1 | ACTB, ACTG1, ARHGEF2, ARPC1A, ARPC1B, ARPC2, ARPC4, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, HCLS1, KRT18, LOC100506658, LY96, NCK1, NCK2, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ |
| KEGG:04614 | Renin-angiotensin system | 6,88E-09 | 6 | AGT, MAS1 | ACE, ACE2, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MME, NLN, REN, THOP1 |
| KEGG:05020 | Prion diseases | 1,45E-10 | 1 | NOTCH1, C9, SOD1, PRNP | BAX, C1QA, C1QB, C1QC, C5, C6, C7, C8A, C8B, C8G, CCL5, EGR1, ELK1, FYN, HSPA1A, HSPA5, IL1A, IL1B, IL6, LAMC1, LOC100506742, MAP2K1, MAP2K2, MAPK1, MAPK3, NCAM1, NCAM2, PRKACA, PRKACB, PRKACG, PRKX, STIP1 |
Analysis with in the CIS subgroup revealed the important pathways in the transmission of disease subtypes. MS suggestive CIS (MSs-CIS) group indicated the importance of Aldosterone regulated sodium reabsorption pathway. Single attack (SA-MS) showed the increased activation of NOD-like receptor signaling pathway and clinically definite MS (CDMS) showed shared pathways with RRMS and CIS subtypes.