Identification of Mycobacterium tuberculosis Antigens with Vaccine Potential Using a Machine Learning-Based Reverse Vaccinology Approach
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Novel Protective Antigens Predicted by Vaxign-ML
3.2. Antigens Belonging to Protein Families of Previously Established MTB PAgs
3.3. Antigens Having Biological Processes Associated with MTB Virulence or LTBI
3.4. Antigens with the Greatest Number of Promiscuous MHC-I and MHC-II Epitopes
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein Family | Protein | Tuberculist ID |
---|---|---|
mycobacterial A85 antigen | FbpC (Ag85C) | Rv0129c |
mycobacterial PE | PE_PGRS11 | Rv0754 |
PE4 | Rv0160c | |
PE26 | Rv2519 | |
mycobacterial PPE | Hypothetical protein Rv3822 | Rv3822 |
PPE28 | Rv1800 | |
PPE8 | Rv0355c | |
PPE12 | Rv0755c | |
PPE30 | Rv1802 | |
peptidase S1C | HtrA | Rv1223 |
PepD | Rv0983 | |
PstS | PstS2 | Rv0932c |
RsiV | Hypothetical protein Rv3036c | Rv3036c |
WXG100 | EsxI | Rv1037c |
Biological Process Category | Proteins (Tuberculist IDs) |
---|---|
Cell envelope biogenesis and maintenance | PonA2 (Rv3682), PonA1 (Rv0050), FadD15 (Rv2187), LdtB (Rv2518c), PbpB (Rv2163c), FadD30 (Rv0404), FbpC (Ag85C) (Rv0129c), AccD4 (Rv3799c), FadD32 (Rv3801c), hypothetical protein Rv3811 (Rv3811), LprQ (Rv0483), PbpA (Rv0016c), FadD19 (Rv3515c) |
DNA Repair | RecA (Rv2737c), HtpG (Rv2299c), UvrA (Rv1638), LigD (Rv0938), RecG (Rv2973c), UvrB (Rv1633) |
Interaction with host immune system | FadE5 (Rv0244c), Mce1A (Rv0169), probable aldehyde dehydrogenase (Rv0458), CaeA (Rv2224c), LprA (Rv1270c), FadD30 (Rv0404), EccCa1 (Rv3870), Icl1 (Rv0467), PknH (Rv1266c), MmpL12 (Rv1522c), UvrB (Rv1633), EccB1 (Rv3869), halimadienyl diphosphate synthase (Rv3377c), FadD19 (Rv3515c) |
Fatty acid beta-oxidation | FadB (Rv0860), FadA3 (Rv1074c), Ltp1 (Rv2790c), probable nonspecific lipid-transfer protein (Rv1627c) |
Growth in host | FadD13 (Rv3089), Mce2C (Rv0591), Mce4A (Rv3499c), Mce1A (Rv0169), Mce1F (Rv0174), Tgs4 (Rv3088), Mce3C (Rv1968), Mce1C (Rv0171), Mce3D (Rv1969), Mce3A (Rv1966), EccCa (Rv3870), Mce4C (Rv3497c), Mce2F (Rv0594), Mce4D (Rv3496c), Mce2A (Rv0589), EccA1 (Rv3868), Mce2D (Rv0592), Mce1D (Rv0172), FadA (Rv0243), Mce4F (Rv3494c) |
Protein folding | GroEL2 (Rv0440), Mpa (Rv2115c), GroEL1 (Rv3417c), ClpX (Rv2457c), HtpG (Rv2299c), ClpB (Rv0384c) |
Response to antibiotic | PonA2 (Rv3682), GyrB (Rv0005), RecA (Rv2737c), RpoB (Rv0667), PonA1 (Rv0050), FbpC (Ag85C) (Rv0129c), possible penicillin-binding lipoprotein (Rv2864c), PepD (Rv0983), IleS (Rv1536), LprG (Rv1411c) |
Response to acidic pH | FadD13 (Rv3089), Tgs4 (Rv3088), Icl1 (Rv0467), AccD4 (Rv3799c) |
Response to hypoxia | GroEL2 (Rv0440), PonA1 (Rv0050), Tgs4 (Rv3088), Icl1 (Rv0467), AccD4 (Rv3799c), PE_PGRS11 (Rv0754), Tuf (Rv0685), SdhA (Rv3318), probable succinate dehydrogenase (Rv0248c) |
Response to nitrosative or oxidative stress | Mpa (Rv2115c), FtsH (Rv3610c), HtpG (Rv2299c), Tgs4 (Rv3088), Mpt53 (Rv2878c), AccD4 (Rv3799c), UvrB (Rv1633), CysN (Rv1286) |
Response to starvation | halimadienyl diphosphate synthase (Rv3377c), PknD (Rv0931c), CysN (Rv1286) |
Protein | Tuberculist ID | GO Biological Process | Subcellular Location | MHC-I Promiscuous Epitopes | MHC-II Promiscuous Epitopes |
---|---|---|---|---|---|
Having highest numbers of both MHC-I and MHC-II promiscuous epitopes | |||||
PPE8 | Rv0355c | not available | not available | 104 | 194 |
IleS | Rv1536 | isoleucyl-tRNA aminoacylation, response to antibiotics | cytoplasm | 92 | 156 |
MmpL12 | Rv1522c | response to host immune response | cell membrane, multi-pass membrane protein | 86 | 263 |
UvrA | Rv1638 | cellular response to DNA damage stimulus, negative regulation of strand invasion, nucleotide-excision repair, SOS response | cytoplasm | 73 | 116 |
RpoB | Rv0667 | response to antibiotic, DNA-templated transcription | cell wall, cytosol, plasma membrane | 72 | 109 |
ClpB | Rv0384c | protein refolding, response to heat | cytoplasm | 62 | 104 |
Having highest number of MHC-I promiscuous epitopes only | |||||
PonA2 | Rv3682 | peptidoglycan biosynthetic process, response to antibiotic | not available | 60 | 88 |
FadE5 | Rv0244c | response to host immune response | extracellular region, plasma membrane | 57 | 86 |
Mce2D | Rv0592 | growth of symbiont in host, growth of symbiont in host vacuole | cell wall | 57 | 84 |
FadD30 | Rv0404 | Actinobacterium-type cell wall biogenesis, fatty acid biosynthetic process, induction by symbiont of host immune response, lipid biosynthetic process | not available | 56 | 85 |
EccCa1 | Rv3870 | evasion of host immune response, growth of symbiont in host, pathogenesis, protein secretion by the type VII secretion system | cell inner membrane, multi-pass membrane protein | 56 | 79 |
Having highest number of MHC-II promiscuous epitopes only | |||||
PPE28 | Rv1800 | not available | not available | 54 | 176 |
PE4 | Rv0160c | not available | not available | 48 | 100 |
FadD15 | Rv2187 | Actinobacterium-type cell wall biogenesis, fatty acid biosynthetic process, lipid biosynthetic process, long-chain fatty acid metabolic process | cell wall, plasma membrane | 48 | 113 |
PknD | Rv0931c | cellular response to phosphate starvation, negative regulation of catalytic activity, negative regulation of fatty acid biosynthetic process, negative regulation of protein binding, pathogenesis, positive regulation of catalytic activity | cell membrane, single-pass membrane protein | 42 | 105 |
Mce2A | Rv0589 | growth of symbiont in host, growth of symbiont in host vacuole | integral component of membrane | 36 | 100 |
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Teahan, B.; Ong, E.; Yang, Z. Identification of Mycobacterium tuberculosis Antigens with Vaccine Potential Using a Machine Learning-Based Reverse Vaccinology Approach. Vaccines 2021, 9, 1098. https://doi.org/10.3390/vaccines9101098
Teahan B, Ong E, Yang Z. Identification of Mycobacterium tuberculosis Antigens with Vaccine Potential Using a Machine Learning-Based Reverse Vaccinology Approach. Vaccines. 2021; 9(10):1098. https://doi.org/10.3390/vaccines9101098
Chicago/Turabian StyleTeahan, Blaine, Edison Ong, and Zhenhua Yang. 2021. "Identification of Mycobacterium tuberculosis Antigens with Vaccine Potential Using a Machine Learning-Based Reverse Vaccinology Approach" Vaccines 9, no. 10: 1098. https://doi.org/10.3390/vaccines9101098