TABLE 1.
Protein prediction in the 95th percentile
| Categorya | COG(s) | Gene(s) | Protein information |
|---|---|---|---|
| Cellular processes and signaling [D],[M],[N],[O],[T],[U],[V],[W],[Y],[Z]b | D | vapB47 | Antitoxin, TA group |
| M | gid (6) | Associated with streptomycin resistance | |
| M | murD | Peptidoglycan biosynthesis | |
| O | prcA c | Intermediary metabolism and respiration | |
| T | pstP c | Regulatory proteins | |
| T | mazF3 | Toxin, TA group | |
| U | tatBc (35) | Probable transmembrane transporter | |
| Information storage and processing [A],[B],[J],[K],[L]b | J | tsnR, mihF | Information pathways |
| J | tadA | CMP-type deaminase domain protein | |
| K | mce1R, mprA, pknJ | Regulatory proteins | |
| K | cspA | Cold shock protein | |
| L | gyrA (6) | Associated with quinolone resistance | |
| L | ligC | DNA recombination and repair | |
| Metabolism [C],[E],[F],[G],[H],[I],[P],[Q]b | C, H | fadH,c idsB | Lipid metabolism |
| C, G, Q | cyp132,c cyp51,c ppdK,c fucA, opcA | Intermediary metabolism and respiration | |
| C, E | aroG,c glpQ1,c lldD2,c mpt53, gcvH | Intermediary metabolism and respiration | |
| E | proX | Transmembrane transporter activity | |
| E | aroG, cysK2, trpG,c serB2c | Amino acid biosynthesis | |
| F | purF | Purine biosynthesis/purine salvage | |
| F, P | ddlA,c ceoB, uspA, pstA1, pitAc | Cell wall and cell processes | |
| F, I, G, H | guaB3,c lipR, idi, impA | Intermediate metabolism and respiration | |
| H | ribC, cobD, cobL | Riboflavin/cobalamin biosynthesis | |
| H, I | accD4,c fadD5, fadE32 | Involved in lipid metabolism | |
| H, I | fadE33, pssA, fabG3 | Involved in lipid metabolism | |
| I, H | lspF,c grcC2, lipJ | Intermediate metabolism and respiration | |
| P | pstA1, cysW c | Transmembrane transporter activity | |
| P | bfrB | Iron storage protein | |
| Q | mce3C (25) | Virulence factor, Mce family | |
| Q | yrbE2A | Part of mce2 operon | |
| Poorly characterized [R],[S]b | S | apa | Immunogenic, cell wall and cell processes |
| S/UC | hsaB | Cholesterol catabolism | |
| S.UC | vapC38, vapC40, vapB19, mazF8 | TA group | |
| S/UC | lppA, lppB, lpqQ, lppO | Possible lipoproteins | |
| Unable to characterize (UC) | S/UC | esxO, esxL, esxW | ESAT-6-like protein |
| S/UC | espK | ESX-1 secretion system | |
| S/UC | mmpS3 | Determinant of intrinsic M. tuberculosis AMR |
Classification of clusters of orthologous protein groups (COGs) in the 95th percentile, combined with information from Mycobrowser (18) and UniProt (19). Additional information from the literature is individually cited within the table. Genes related to basic COG categories (e.g., metabolism) were observed in both percentiles. However, certain families, such as the fadD and fadE genes (e.g., fadE33, fadD5, fadE32), associated with fatty acid and cholesterol metabolism, were observed only in the 95th percentile (17). Genes related to pathogenesis of TB disease (e.g., ESAT-6/ESX genes) and antibiotic resistance (e.g., gyrA, gidB) are present. ESAT-6/ESX family genes were predicted as poorly characterized. The classification-involved proteins encoded by genetically characterized genes with reference to H37Rv. Protein prediction for the noncharacterized genes can be found in Data Set S1 in the supplemental material.
COG subcategories are explained analytically in the legend to Table S2 in the supplemental material.
A number of genes have been identified as high-confidence drug targets (22).