Table 2.
Interactome model predicted protein–protein interactions (PPIs) between bovine host and B. melitensis pathogen.
| B. melitensis gene | B. melitensis gene description | Normalized correlation weight | Bovine host gene | Bovine Gene Description | Host gene significantly perturbed | Prediction type | Perturbed Host Pathways |
|---|---|---|---|---|---|---|---|
| MotB BMEI0324 (BME_RS01570) | Chemotaxis MotB protein | 0.268 | JUN | jun oncogene | Yes | PD | Toll-like receptor, MAPK, Epithelial cell signaling, GnRH signaling, ErbB signaling, Wnt signaling, BRC signaling, B cell receptor, T cell receptor |
| MotB BMEI0324 (BME_RS01570) | −0.221 | ROCK2 | Rho-associated, coiled-coil containing protein kinase 2 | Yes | PD | Regulation of actin cytoskeleton, Axon guidance, Integrin-mediated cell adhesion, TGF-beta signaling, CCR@ signaling, Wnt signaling | |
| BMEI0717 (BME_RS03560) | 22 kDa OMP precursor | 0.208 | BAD | BCL2-antagonist of cell death | Yes | BSS | Trefiol Factors Mucosal Healing, VEGF signaling, Apoptosis |
| BMEI0717 (BME_RS03560) | 0.188 | MAP2K3 | Mitogen-activated protein kinase kinase 3 | Yes | BSS | MAPK, GnRH, Toll-like receptor, Fc epsilon RI signaling, Integrin-mediated cell adhesion | |
| BMEI0890 (BME_RS04435, tgt) | tRNA guanosine transglycosylase | 0.159 | RAP1A | RAP1A, member of RAS oncogene family | No | BSS | MAPK, Integrin-mediated cell adhesion, Leukocyte transendothelial migration |
| BMEI1077 (BME_RS05395) | Immunogenic membrane protein YajC | −0.206 | NRAS | Neuroblastoma RAS viral (v-ras) oncogene homolog | Yes | PD | ErbB signaling, Regulation of actin cytoskeleton, Natural killer cell mediated cytotoxicity, Tight junction, Fc epsilon RI signaling, T cell receptor signaling, GnRH signaling |
| BMEI1077 (BME_RS05395) | −0.225 | CBL | Cas-Br-M (murine) ecotropic retroviral tranforming sequence | No | PD | Jak-Stat signaling, ErbB signaling, Insulin signaling, T cell receptor signaling | |
| BMEI1077 (BME_RS05395) | −0.238 | RHOA | ras homolog gene family, member A | Yes | PD | Trefoil factors, Tight junction, TGF-beta signaling, Wnt signaling, Adherens junction, Integrin-mediated cell adhesion, etc. | |
| BMEI1086 (BME_RS05450) | Segregation and condensation protein A | −0.214 | CRKL | v-crk sarcoma virus CT10 oncogene homolog | No | BSS | Regulation of actin cyctoskeleton, Insulin signaling, ErbB signaling, MAPK |
| BMEI1582 (BME_RS07890, narL) | Two-component system nitrate/nitrite response regulator | 0.145 | MKNK1 | MAP kinase interacting serine/threonine kinase 1 | Yes | BSS | MAPK, Insulin signaling |
| BMEI1751 (BME_RS08690) | LuxR family transcriptional regulator | −0.102 | IRF3 | Interferon regulatory factor 3 | No | BSS | Toll-like receptor signaling |
| BMEI1846 (BME_RS09140) | Response regulator receiver protein ExsF | 0.202 | FLNA | Fliamin A, alpha (Actin binding protein 280) | Yes | BSS | MAPK |
| BMEI1846 (BME_RS09140) | −0.157 | CRK | v-crk sarcoma virus CT10 oncogene homolog | Yes | BSS | Regulation of actin cytoskeleton, Insulin signaling, ErbB signaling, MAPK, Integrin-mediated cell adhesion | |
| BtaE (BMEI1873) | trimeric autotransporter adhesin | −0.018 | NFKBIA | nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha | No | PD | CD40L Signaling, Apoptosis, Toll-like receptor signaling, Adipocytokine signaling, Epithelial cell signaling in Helicobacter pylori infection, Chronic myeloid leukemia, Prostate cancer, T cell receptor signaling with Antigen Processing, B cell receptor signaling, T cell receptor signaling |
| BtaE (BMEI1873) | 0.035 | NFATC2 | nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 | No | PD | Wnt signaling, VEGF signaling, T cell receptor signaling with Antigen Processing, T cell receptor signaling, MAPK signaling, Calcium signaling, Natural killer cell mediated cytotoxicity, Axon guidance | |
| BtaE | −0.037 | MAPK8IP1 | mitogen-activated protein kinase 8 interacting protein 1 | No | MAPK signaling | ||
| BtaE | 0.014 | RRAS2 | related RAS viral (r-ras) oncogene homolog 2 | No | BSS | Regulation of actin cytoskeleton, MAPK signaling, Insulin signaling, Axon guidance, Long-term depression, T cell receptor signaling, Natural killer cell mediated cytotoxicity, Gap junction, Tight junction, B cell receptor signaling, Long-term potentiation | |
| BtaE | 0.03 | RAC3 | ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) | No | BSS | Integrin-mediated cell adhesion, Colorectal cancer, Pancreatic cancer, VEGF signaling, MAPK signaling, Fc epsilon RI signaling, Toll-like receptor signaling, Regulation of actin cytoskeleton, Adherens junction, Wnt signaling, B cell receptor signaling, Axon guidance | |
| BtaE | −0.028 | CCND1 | cyclin D1 | No | BSS | Colorectal cancer, Wnt signaling, Acute myeloid leukemia, Thyroid cancer, Prostate cancer, Endometrial cancer, Non-small cell lung cancer, Chronic myeloid leukemia, Bladder cancer, Glioma, Pancreatic cancer, Melanoma, Small cell lung cancer, Jak-STAT signaling, Cell cycle | |
| BMEI1872 (BME_RS09280) | Cell surface protein | −0.153 | JUND | jun D proto-oncogene | Yes | BSS | MAPK |
| BMEII0035 (BME_RS10365, virB11) | P-type DNA transfer ATPase VirB11 | −0.134 | PIK3R2 | Phosphoinositide 3 kinase, regulatory subunit 2 | Yes | BSS | T cell receptor, mTOR signaling, VEGF signaling, ErbB signaling, Toll-like receptor, Apoptosis, Jak-STAT signaling, Phosphatidylinositol signaling, etc. |
| BMEII0035 (BME_RS10365, virB11) | −0.168 | MAPK8IP1 | Mitogen-activated protein kinase 8 interacting protein 1 | Yes | PD | MAPK | |
| BMEII0926 (BME_RS14720, minD) | Septum site-determining protein MinD | 0.121 | RASGRP3 | RAS guanyl releasing protein 3 | Yes | BSS | MAPK, B cell receptor signaling |
| BMEII0926 (BME_RS14720, minD) | 0.102 | CBLB | Cas-Br-M (murine) ecotropic retroviral tranforming sequence | Yes | BSS | T cell receptor signaling, Insulin signaling, ErbB signaling, Jak-STAT signaling | |
| BMEII0951 (BME_RS14810, narH) | Nitrate reductase beta subunit | 0.13 | CRK | v-crk sarcoma virus CT10 oncogene homolog | Yes | BSS | Regulation of actin cytoskeleton, Insulin signaling, ErbB signaling, MAPK, Integrin-mediated cell adhesion |
| BMEII1085 (BME_RS15470, flgA) | Flagellar basal body P-ring biosynthesis protein FlgA | 0.116 | CASP4 | Caspase 4, apoptosis-related cysteine peptidase | No | BSS | MAPK |
| BMEII1085 (BME_RS15470, flgA) | −0.105 | CASP3 | Caspase 3, apoptosis-related cysteine peptidase | Yes | BSS | Apoptosis, MAPK, Natural killer cell mediated cytotoxicity | |
| BMEII1113 (BME_RS15605, fliG) | Flagellar motor switch protein FliG | −0.112 | MAP4K1 | Mitogen-activated protein kinase kinase kinase kinase 1 | Yes | BSS | MAPK |
Higher evidence of possible interaction is inferred if the host gene is also significantly perturbed and correlated with the pathogen gene expression. Prediction type of “Protein Domain” (PD) means that the same binding domains exist between host-pathogen proteins. “Binding sequence similarity” (BSS) is achieved by finding similar sequence in the pathogen as a binding protein domain existing in the host protein. Correlation weights have been normalized so that comparisons between different pathways can be made. The pathways which contain the host PPI genes are listed for each PPI pair. Both the in vivo pathogen and host gene expressions were employed in training the models for learning the PPIs.