Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle
Abstract
1. Introduction
Master Regulators as Drug Targets
2. Materials and Methods
2.1. Gene Sets
2.2. Microarray Data Set
2.3. Monotonically Expressed Genes
2.4. Finding Master Regulators and Over-Represented Pathways
3. Results
3.1. Master Regulator Analysis
3.1.1. Master Regulators in Liver
3.1.2. Master Regulators in Spleen
3.1.3. Master Regulators in Lymph Node
3.2. Pathway Analyses
3.2.1. Over-Represented Pathways Found for Liver Tissue
3.2.2. Over-Represented Pathways Found for Spleen Tissue
3.2.3. Over-Represented Pathways Found for Lymph Node Tissue
3.3. Analysis of Gene Expression Profiles of DBP and MYC
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Boran | N’Dama | |||
---|---|---|---|---|
Ascending | Descending | Ascending | Descending | |
Liver | 741 | 308 | 757 | 124 |
Spleen | 669 | 126 | 13 | 139 |
Lymph node | 87 | 5 | 119 | 114 |
Boran | N’Dama | |
---|---|---|
Liver | MYC, E2F1, PPARG | DBP, PBX1, HOXA4, PPARA |
Spleen | PITX2, E2F1, PBX1 | PBX1 |
Lymph node | MYC, pSTAT1, PBX1 | DBP, PPARA |
Liver | |||
---|---|---|---|
Pathway Name | Hit Names | Adjusted p-Value | |
Boran | Cellular responses to external stimuli | Arnt, Fos, Hif1a, Hsf1 | 4.64 × 10 |
Regulation of beta-cell development | Foxo1, Hnf4g, Nkx2.2 | 0.0032 | |
Regulation of Hypoxia-inducible Factor (HIF) by oxygen | Arnt, Hif1a | 0.0033 | |
Cellular response to hypoxia | Arnt, Hif1a | 0.0033 | |
Signaling by TGF-beta Receptor Complex | Myc, Smad3, Smad4 | 0.0036 | |
Signaling by TGF-beta family members | Myc, Smad3, Smad4 | 0.0063 | |
Signaling by NOTCH1 | Hif1a, Myc | 0.0105 | |
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | Myc, Smad4 | 0.0147 | |
Signaling by NOTCH | Hif1a, Myc | 0.0349 | |
Interleukin-1 family signaling | Nfkb1, Smad3 | 0.0371 | |
Cellular Senescence | Fos, Jun | 0.0416 | |
N’Dama | PTEN Regulation | Atf, Jun | 0.0025 |
Activation of HOX genes during differentiation | Hoxa4, Jun, Meis1 | 0.0036 | |
Activation of anterior HOX genes in hindbrain development during early embryogenesis | Hoxa4, Jun, Meis1 | 0.0036 | |
BMAL1:CLOCK, NPAS2 activates circadian gene expression | Dbp, Ppara | 0.0161 | |
PIP3 activates AKT signaling | Atf, Jun | 0.0229 | |
Transcriptional regulation of pluripotent stem cells | Pbx1, Pou5f1 | 0.0229 | |
Intracellular signaling by second messengers | Atf2, Jun | 0.0280 | |
Transcriptional regulation by RUNX2 | Sox9, Stat1 | 0.0364 | |
Transcriptional regulation of white adipocyte differentiation | Pparg, Rxra | 0.0424 | |
Circadian Clock | Dbp, Ppara | 0.0488 |
Spleen | |||
---|---|---|---|
Pathway Name | Hit Names | Adjusted p-Value | |
Boran | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | Pou5f1, Stat3 | 0.0034 |
N’Dama | Oxidative Stress Induced Senescence | Fos, Jun | 0.0033 |
BMAL1:CLOCK NPAS2 activates circadian gene expression | Dbp, Ppara | 0.0052 | |
MAPK6/MAPK4 signaling | Foxo1, Jun | 0.0052 | |
Signaling by NOTCH3 | Hes1, Pbx1 | 0.0052 | |
Cellular responses to stress | Fos, Hsf1, Jun | 0.0062 | |
Fc epsilon receptor (FCERI) signaling | Fos, Jun | 0.0067 | |
Cellular responses to external stimuli | Fos, Hsf1, Jun | 0.0135 | |
MAPK family signaling cascades | Foxo1, Jun | 0.0166 | |
Circadian Clock | Dbp, Ppara | 0.0166 | |
Signaling by NOTCH | Hes1, Pbx1 | 0.0203 | |
Generic Transcription Pathway | E2f1, Hes1, Sox9, Stat1, Tead1 | 0.0243 | |
Cellular Senescence | Fos, Jun | 0.0243 | |
RNA Polymerase II Transcription | E2f1, Hes1, Sox9, Stat1, Tead1 | 0.0350 | |
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) | PPara, Rxra | 0.0432 |
Lymph Node | |||
---|---|---|---|
Pathway Name | Hit Names | Adjusted p-Value | |
Boran | MAP kinase activation in TLR cascade | Atf1, Atf2, Fos, Jun, Nfkb1 | 2.37 |
Interleukin-17 signaling | Atf1, Atf2, Fos, Jun, Nfkb1 | 1.83 × 10 | |
MAPK targets/ Nuclear events mediated by MAP kinases | Atf1, Atf2, Fos, Jun | 3.66 × 10 | |
MyD88 cascade initiated on plasma membrane | Atf1, Atf2, Fos, Jun, Nfkb1 | 5.54 × 10 | |
MyD88 dependent cascade initiated on endosome | Atf1, Atf2, Fos, Jun, Nfkb1 | 7.62 × 10 | |
MyD88:Mal cascade initiated on plasma membrane | Atf1, Atf2, Fos, Jun, Nfkb1 | 1.03 × 10 | |
MyD88-independent TLR4 cascade | Atf1, Atf2, Fos, Jun, Nfkb1 | 2.27 × 10 | |
Toll Like Receptor 3 (TLR3) Cascade | Atf1, Atf2, Fos, Jun, Nfkb1 | 2.88 × 10 | |
Toll-Like Receptors Cascades | Atf1, Atf2, Fos, Jun, Nfkb1 | 4.39 × 10 | |
MAPK6/MAPK4 signaling | Foxo1, Jun, Myc | 4.66 × 10 | |
Innate Immune System | Atf1, Atf2, Fos, Jun, Ltf, Nfkb1 | 9.27 × 10 | |
Signaling by Interleukins | Atf1, Atf2, Fos, Jun, Nfkb1, Stat1, Stat3 | 0.0010 | |
PTEN Regulation | Atf2, Jun | 0.0016 | |
MAPK family signaling cascades | Foxo1, Jun, Myc | 0.0028 | |
Oxidative Stress Induced Senescence | Fos, Jun | 0.0069 | |
Cytokine Signaling in Immune system | Atf1, Atf2, Fos, Jun, Nfkb1, Stat1, Stat3 | 0.0081 | |
Fc epsilon receptor (FCERI) signaling | Fos, Jun | 0.0138 | |
PIP3 activates AKT signaling | Atf2, Jun | 0.0154 | |
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | Myc, Smad4 | 0.0171 | |
NGF signalling via TRKA from the plasma membrane | Atf1, Stat3 | 0.0171 | |
Intracellular signaling by second messengers | Atf2, Jun | 0.0189 | |
Immune System | Atf1, Atf2, Fos, Jun, Ltf, Nfkb1, Relb, Stat1, Stat3 | 0.0241 | |
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | Mybl2, Myc | 0.0311 | |
Generic Transcription Pathway | E2f1, Mybl2, Myc, Smad4, Sox9, Stat1 | 0.0338 | |
Mitotic G2-G2/M phases | Foxm1, Mybl2 | 0.0381 | |
Mitotic G1-G1/S phases | E2f1, Mybl2 | 0.0381 | |
Interleukin-1 family signaling | Nfkb1, Stat3 | 0.0430 | |
Signaling by TGF-beta Receptor Complex | Myc, Smad4 | 0.0456 | |
Cellular Senescence | Fos, Jun | 0.0482 | |
N’Dama | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | Pou5f1, Stat3 | 0.0042 |
BMAL1:CLOCK, NPAS2 activates circadian gene expression | Dbp, Ppara | 0.0078 | |
Circadian Clock | Dbp, Ppara | 0.0244 | |
Factors involved in megakaryocyte development and platelet production | Irf1, Irf2 | 0.0354 | |
Interleukin-12 family signaling | Stat1, Stat3 | 0.0375 |
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Rajavel, A.; Schmitt, A.O.; Gültas, M. Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle. Int. J. Mol. Sci. 2021, 22, 562. https://doi.org/10.3390/ijms22020562
Rajavel A, Schmitt AO, Gültas M. Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle. International Journal of Molecular Sciences. 2021; 22(2):562. https://doi.org/10.3390/ijms22020562
Chicago/Turabian StyleRajavel, Abirami, Armin Otto Schmitt, and Mehmet Gültas. 2021. "Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle" International Journal of Molecular Sciences 22, no. 2: 562. https://doi.org/10.3390/ijms22020562
APA StyleRajavel, A., Schmitt, A. O., & Gültas, M. (2021). Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle. International Journal of Molecular Sciences, 22(2), 562. https://doi.org/10.3390/ijms22020562