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In total, 319 subjects were enrolled in the final analysis, which consisted of 94 healthy controls, 113 LTBI subjects, and 112 active TB patients. Both demographic and clinical characteristics of all subjects in this study are shown in Table 1. In the healthy control, LTBI, and active TB groups, median ages were 40.5 years (range, 18-65 years), 45 years (range, 20-69 years), and 42 years (range, 18- 65 years), respectively; the male to female ratios were 44/50, 46/67, and 53/59, respectively, and there were no statistical differences among them with respect to age (P = 0.268) or gender (P = 0.600). For the T-spot TB assay, results for healthy controls and LTBI subjects were negative and positive, respectively. Furthermore, the T-spot TB assay detected 89 out of 93 patients with active TB, indicating a sensitivity of 95.7%. In addition, none of the subjects was infected with HIV or was treated with immunosuppressive medications.
Items Health Controls LTBI Subjects Active TB Patients Total number 94 113 112 Median age (range), years 40.5 (18-65) 45 (20-69) 42 (18-65) Gender, male/female 44/50 46/67 53/59 Abnormal chest radiograph, n (%) 0 (0) 0 (0) 112 (100.0) Bacteria positive, n (%) nd nd 112 (100.0) TST results Induration < 5 mm, n (%) 94 (100.0) 0 (0) nd Induration 5-10 mm, n (%) 0 (0.0) 0 (0) nd Induration > 10 mm, n (%) 0 (0.0) 113 (100.0) nd T-SPOT results Positive, n (%) 0 (0) 113 (100.0) 89 (79.5) Negative, n (%) 94 (100.0) 0 (0) 4 (3.6) Unknown, n (%) 0 (0) 0 (0) 19 (16.9) No immunosuppression, n (%) 94 (100.0) 113 (100.0) 112 (100.0) HIV-negative, n (%) 94 (100.0) 113 (100.0) 112 (100.0) Note. n, number of subjects; nd, not done. Table 1. Demographic Characteristics and Clinical Details of Study Subjects
Among these subjects, we randomly selected 20 each of LTBI and active TB patients as the screening population (screening using microarray), and 94 healthy controls, 93 LTBI individuals, and 92 active TB patients as the validation population (validation using indirect ELISA).
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After normalizing and excluding the outlier microarrays, 18 and 19 microarray results were obtained from LTBI subjects and active TB patients, respectively. We further revealed that the concentrations of 152 Mtb antigen-specific IgG antibodies were significantly higher in active TB patients than in LTBI subjects based on a P value of < 0.05 and a fold-change (Log2) of > 0.18 (Supplementary Table S1, available in www.besjournal.com). Moreover, the differences in IgG reactivity against 152 antigens in each individual serum from LTBI individuals and active TB patients were subjected to hierarchical clustering, which distinguished between LTBI and active TB patients (Figure 1).
Name L1 L2 L3 L5 L6 L7 L8 L9 L10 L11 L12 L13 L14 L15 L16 L18 L19 L20 A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 A11 A12 A13 A14 A15 A16 A18 A19 A20 Fold change (Log2) P value Rv0379 8.3491782 6.2903204 5.8762276 6.4405914 8.0420408 8.0936946 7.2329981 8.2203904 6.3279363 6.1181267 6.0957997 8.1158571 8.3239144 7.2287831 7.8648127 6.7331704 8.9338898 6.6794144 7.2813882 9.6584977 9.926081 8.978122 7.2564087 8.4931519 8.1520579 9.4238362 10.673998 8.0820386 10.70095 10.954123 11.99734 8.8251697 8.4082266 12.650203 13.758344 10.723222 8.730426 0.417770064 7.77E-06 Rv3841 10.242245 7.5800733 7.3498213 7.9971314 5.769736 5.7702772 6.5681823 8.5151497 7.9835148 7.5627985 7.1648398 7.7810613 6.2780138 6.0762377 7.4515165 7.3758343 9.9470853 7.7492584 8.6136389 7.8690714 12.044714 8.8265217 7.277246 10.129875 10.998924 11.232083 9.7009306 11.393826 7.3199922 9.9914507 10.082166 7.4819171 11.212392 13.575217 10.417595 9.4470854 12.577226 0.414755188 1.19E-05 Rv3190c 7.3733508 10.413173 8.2969942 9.3483153 7.211019 7.0578386 9.8147715 10.394686 8.8763918 6.5270723 8.0658541 7.6952589 8.5519846 8.7706159 9.9645737 8.847094 9.2181983 7.0162382 10.460602 12.296939 12.081969 11.391606 8.7558325 11.669257 10.506195 10.830471 12.162605 11.327933 11.515915 10.767905 10.758721 12.162605 10.431843 11.937504 12.879088 11.866002 11.619375 0.411458656 2.56E-09 Rv1483 7.5987427 7.8879505 8.2757547 8.3816482 8.5845724 8.9781705 8.2235729 8.5734425 8.6782129 8.9804309 9.2148661 7.7636504 9.0467124 8.1103122 8.8035498 8.0204223 8.2460404 7.7236564 8.4237559 13.38782 9.5768292 12.223228 8.0706537 12.774646 11.669257 12.223228 9.7485006 11.717555 12.78021 10.183723 9.5593928 13.758344 13.055373 8.8211599 10.932973 9.0805367 12.78021 0.402224709 2.14E-06 Rv2421c 7.6369405 6.8505005 6.7417458 6.6739014 7.4019211 8.1896234 8.3399418 6.1467534 6.5496445 7.3007739 6.4734575 7.7981635 8.1674519 8.2403259 5.8872593 6.7898572 7.4638011 6.3679218 7.3717442 10.810575 7.8538797 10.761906 6.9394494 11.900448 11.818093 9.4977798 8.2811393 10.249528 10.617704 7.9095422 7.7042669 11.397897 11.964498 8.0913551 7.6245142 8.1119663 10.257515 0.39568212 1.29E-05 Rv2928 7.9087819 6.2613301 6.4972082 6.3740435 7.89223 6.0244463 6.2438668 6.1479758 6.1387066 5.5851077 5.8009375 7.2937137 6.1143934 5.9447971 8.93555 7.2742685 7.8035326 6.3854338 8.200557 9.8401148 7.7653934 8.7575554 9.1251269 9.612247 9.0481595 8.7989169 7.7661579 8.8489326 8.7617273 7.4317456 8.9788697 9.1823419 8.6317904 7.9098749 8.2401753 7.8592369 9.797653 0.370036401 1.75E-08 Rv2031c 6.8208515 6.0546301 6.6727487 6.2191481 7.613001 5.9213299 5.929078 6.8054547 6.1683855 5.8917976 5.8289113 6.8902455 6.0886513 6.3874929 6.3016622 6.7289734 6.8315949 6.6077193 7.8176054 6.9309494 9.8984299 7.2827637 7.9252977 7.2249701 6.9253877 7.1038611 8.0433612 8.6644635 7.3034878 8.5580843 8.0124233 8.7103341 6.2055835 9.753778 9.3805067 8.0939956 13.38782 0.363653005 4.22E-05 Rv1474c 8.3250528 6.1444028 6.0719942 6.7559549 7.1513953 6.9446525 8.5620913 8.147383 6.2801309 6.2463967 6.0483955 8.2758866 6.8428462 7.011195 9.5252871 6.5430932 8.23404 6.6791142 8.5625781 12.398564 8.8342358 8.5431174 6.6355925 12.414698 12.340987 9.3325009 7.9963771 9.7844711 8.4760195 8.1349251 9.1904823 9.0789581 11.158235 7.7818309 9.0035605 7.6839698 8.4922127 0.360116396 4.62E-05 Rv2906c 5.670648 6.327279 6.3668663 6.7221993 6.6263945 7.0177027 5.7891352 8.131681 6.2747419 6.4872235 6.8955154 5.6799853 8.3513581 8.9370752 7.7356504 6.5935761 6.5656697 6.4914207 8.6584187 8.0306532 8.0415102 10.803165 7.2749102 10.505461 8.357535 9.4230551 9.1826597 8.5538826 8.7365247 7.788431 8.5843132 8.7832237 7.6389762 9.4046104 9.2268572 9.3663243 7.646153 0.358525308 1.49E-07 Rv1498A 7.7376025 7.0180888 6.8674103 7.7690789 8.6246687 8.6905627 7.1659917 7.8546747 7.57535 7.0832234 6.9580158 7.5880341 8.7283271 9.1932939 7.1026245 6.5574967 8.5936079 7.0613432 8.0317736 10.494522 9.4296979 10.767905 8.0355265 9.5422647 9.1108183 10.512899 10.311709 12.024334 8.4527651 9.8887725 9.6757966 10.835817 9.0368968 11.063385 9.8706611 9.8981928 9.8207884 0.357088806 1.43E-08 Rv1337 8.5782554 6.2727234 5.5816801 6.389916 7.5152048 7.206287 7.8048974 8.5521464 6.2358644 6.1544031 6.1610989 8.1035621 7.6450087 7.0034073 8.6174032 6.00422 8.9259271 5.9270756 8.203378 9.7051384 8.9904078 9.6792579 8.3792888 8.3175188 8.6804047 9.7072596 9.021254 9.0869422 10.434739 9.7104059 9.0896238 10.136697 7.8915744 9.8101172 8.9776426 9.1188848 8.3546608 0.351451617 2.35E-07 Rv3324c 7.4727605 7.0726695 6.7347435 7.494265 7.0622932 7.6004602 6.4318588 7.9676188 7.4415174 7.1103562 7.6438013 7.0271232 7.8107834 9.1175295 6.60658 6.7754203 9.1467135 6.6200129 7.5476951 9.57369 11.669257 10.319612 6.5313228 9.8938929 9.9814129 9.5191524 9.8728204 9.0152162 8.4757591 8.6581222 9.3206183 9.5126366 10.166692 9.6528761 9.3873205 9.7354009 8.8982876 0.338792973 1.73E-07 Rv3899c 10.878719 8.9422482 9.3892025 8.8869599 8.6031849 6.534539 10.665886 10.60589 8.9458764 9.4684363 10.408274 9.5851356 6.2129768 5.9799666 8.9782375 8.7376968 9.661131 10.605242 10.944664 11.287995 10.814208 10.351259 8.9345342 11.98143 14.476539 10.024501 12.879614 10.756596 10.58048 11.693095 10.863784 11.182093 14.476539 11.211205 11.533673 11.353532 10.744906 0.327969314 1.04E-05 Rv3297 7.7813994 5.6182535 6.1052333 5.4971678 6.9399519 7.9138471 7.4582257 7.483583 5.8763718 5.8471977 5.8221673 7.8600523 8.1197832 7.8561676 7.4640846 5.5979532 8.2422007 6.0720134 8.0403314 8.8512019 8.3494275 8.2443216 9.5103595 8.6813129 8.6925627 8.5906839 8.5278079 8.4594752 8.0076713 9.2347291 8.2846653 8.784727 8.6614981 8.456184 8.3027635 8.3821577 9.1430675 0.323521261 5.32E-07 Rv2097c 7.1916979 8.0109329 7.1209251 8.2490101 7.7300946 7.8408914 6.6585778 9.1217991 7.7163833 6.6072822 7.1135338 7.5074509 8.0719083 6.470887 8.5686616 7.3563087 8.8263803 6.9107803 9.584024 9.8869939 8.6073539 9.4928411 7.6556056 10.170391 10.137253 9.3796335 9.376369 12.780565 9.0023389 7.4385149 9.2407789 10.19675 10.422212 8.7537607 8.2546144 8.990879 9.8349583 0.30866537 1.64E-06 Rv0494 7.9871333 8.2065344 7.7069909 8.1708896 6.8158618 7.3528225 7.8903556 8.4978053 8.1364095 7.6044947 8.0957332 7.6724274 7.8731396 8.2413668 8.0611209 8.2219168 7.9183471 8.4545126 8.2987061 10.240039 12.847623 8.4619199 9.1671807 9.6784715 9.5325174 9.6693619 10.235642 9.524654 11.665861 9.0663128 9.7529722 10.269072 9.4578679 8.8331852 9.3381832 9.4858602 9.9577551 0.298200616 1.64E-07 Rv0187 8.8232853 7.4450685 6.2496276 8.3954547 7.4291489 9.9407169 7.0852199 9.9531627 7.0619347 7.1590189 6.6333529 8.1892439 8.6919428 7.6648694 8.046311 7.8490522 8.8566171 6.8448879 8.4758665 10.68926 9.8569648 9.4281083 8.4161572 9.7596431 10.22339 8.9195598 9.0665249 9.9529185 10.366093 10.262419 9.6431775 9.8977508 10.822424 9.0129456 9.7000577 9.4570823 9.9841484 0.292062114 7.31E-07 Rv0597c 11.471435 9.4059438 9.3330073 8.8470712 7.6300437 6.0939683 12.497314 10.228972 9.1380965 8.9671398 8.2183149 11.583256 6.7136558 8.1024876 9.0254082 8.8890505 10.972541 10.752485 11.052981 12.10235 11.008002 11.282732 9.0388019 11.567553 13.38782 10.274864 11.764286 10.562024 10.681328 12.49461 11.068791 11.237638 12.5251 11.764286 11.852338 11.371153 11.035079 0.286161815 6.11E-05 Rv1815 8.4231501 6.0931732 6.4466628 6.4020118 7.5803447 8.083283 8.0265984 7.7413293 6.2309725 5.8337724 6.0218168 7.6145292 7.7323708 9.2008373 7.9677197 7.0065187 9.4536961 6.6348314 9.1040157 10.081743 8.2111263 9.4701028 7.7411365 9.3235513 9.4654895 9.0096934 9.5749866 8.9370249 8.5939845 8.1308778 8.3638136 9.0004057 8.9712766 9.2722326 8.7338513 8.937261 9.5098547 0.285274474 3.81E-06 Rv2632c 7.2609725 6.2786847 6.1796287 6.7815145 7.2408685 7.409093 6.0971735 7.7032662 6.3827642 5.4731893 5.9219602 6.4990705 7.2025417 7.7612409 8.0567929 6.8574841 6.8046469 6.5785487 8.2931632 8.335863 11.453677 7.9710465 7.4257194 8.904729 8.6462559 8.2870977 8.4169069 7.6898417 7.7675221 7.1668065 8.143752 8.3588517 8.9237831 7.9515688 7.113221 8.0718429 8.2820636 0.281975391 2.08E-06 Rv3743c 6.6502233 6.024088 6.722078 5.9443692 7.9789893 7.7669555 6.8206562 7.5828474 5.9850755 5.9744258 6.1048917 7.0058925 7.0826412 6.8321064 6.1532483 6.5699699 6.4516148 6.8053779 7.0507215 8.1494925 8.1564109 7.8132082 8.0921705 8.5095688 8.4167333 8.2885085 7.683132 8.3211327 8.2282789 8.9239248 7.897236 8.4134169 8.3943236 7.5448296 7.7250497 7.4792636 8.9421417 0.276704901 4.67E-09 Rv0062 6.7147166 5.9921393 6.394957 5.9986691 7.8129309 7.9533142 6.8964188 6.3557954 6.0632925 6.1147847 6.1080683 6.7793326 8.3340954 7.8081895 6.7701384 6.2036511 6.7620538 5.9735531 7.6008308 9.4143069 6.6935892 8.1818485 9.1837559 9.2126708 8.9741816 8.4629102 7.2104237 8.5431751 8.5173887 6.7672277 6.9082414 9.0497581 8.3784739 7.1979036 7.6183087 7.0567969 9.6835929 0.275617138 1.08E-05 Rv2499c 8.2967935 6.8018474 6.7430886 6.9928632 8.179409 8.0111114 6.7178617 7.693924 6.9521883 6.4610722 6.9063655 7.7802629 8.0578754 8.5629183 7.3442559 6.8127903 8.573419 6.8663219 8.1003876 9.4414948 8.8943539 9.3702005 7.8098731 9.2888405 8.9578941 9.0445844 9.3833262 8.9377117 9.1010013 9.1895958 9.1482214 8.3040482 8.9831078 9.2442711 9.2939733 9.2481935 9.1338934 0.275352585 4.98E-09 Rv3625c 7.0110514 7.9440728 6.4800295 6.5230113 7.478578 8.2572199 7.7152385 8.0681928 7.6652661 7.1307919 8.2034697 7.0628218 8.2629301 8.8386944 8.1335389 7.057611 7.8035121 6.9790941 7.9582615 10.077463 9.162567 8.9320983 9.7114333 8.9946485 9.723673 9.5021459 10.174634 8.6894632 7.3940609 8.7478567 9.4020881 10.413173 8.0684958 9.6342418 9.4954779 9.14411 8.6571969 0.269997903 7.37E-08 Rv2716 6.5895907 6.2082826 6.0436056 5.8271377 7.6110127 7.889531 6.0411936 8.1574845 6.2535656 5.8487676 5.9923778 6.2681868 7.8734922 8.0346158 7.9293128 6.7061748 7.0891621 6.8624596 8.5502686 9.6439194 7.1902022 8.0879192 7.4434023 8.7783181 8.4874932 8.608162 7.3825463 8.0779459 8.6618287 7.1893454 7.9558537 9.3019822 8.7243654 7.9429808 8.1339035 7.4556365 9.1993011 0.269758356 2.70E-06 Rv2860c 8.1169528 8.0432543 7.1598019 7.6600741 6.6091469 6.1371048 7.2269755 8.4850046 7.1185467 7.381858 7.2022153 7.9737581 6.6040277 6.2728577 7.8288071 7.1824611 7.9868769 6.4052158 8.549173 9.4045547 8.8484038 8.7673414 6.9505866 9.2501628 8.3369416 8.9117892 9.088763 8.3585195 8.4555793 8.601775 9.3887881 9.2586659 8.9288596 8.8172791 9.2050378 8.6228253 9.3185055 0.268484786 1.80E-08 Rv2026c 9.7893241 6.5708104 7.0704452 6.2262416 8.8888402 9.3426826 8.5995939 9.7759013 6.5333667 6.1847363 6.1353623 8.1832736 6.4721581 6.5966895 9.1808346 7.0119125 9.6262775 7.1293906 10.637107 10.755129 8.2382338 8.8604758 8.0007254 10.567584 12.296939 8.7390976 8.0145894 10.470983 9.112491 8.2285784 8.1214479 9.9312656 11.732927 7.9466698 8.4184455 8.3935577 8.3845358 0.266150071 0.00076452 Rv2903c 6.4740465 7.5415281 7.8384415 7.6180486 7.695041 5.8078409 8.0008196 7.8196254 7.4201731 6.8487366 7.064432 6.4790112 6.1526033 5.9442504 6.964646 7.6029363 7.0539874 7.854384 8.2074165 7.3605666 12.223228 7.4224495 8.57938 9.5238404 9.5327777 10.482553 7.955414 7.7854233 6.8567086 7.7370164 8.8872102 7.601863 9.9645737 8.5866768 9.0159117 7.572625 7.3540316 0.26558796 0.00014869 Rv0861c 7.6315587 6.4010965 6.3577009 7.2350981 8.4332142 6.4675745 7.6684342 8.3030484 6.5684655 6.2587724 6.5173718 7.775154 6.8966653 6.4369037 8.4418728 7.0757974 7.8848781 6.0674394 9.520667 9.2285455 8.4472062 9.1260901 9.315057 7.9824904 8.1315759 7.2711375 9.2470647 8.1281469 8.3540141 7.9686188 9.2823379 7.8387866 8.157792 8.6382553 9.6073351 8.2044902 8.1450955 0.262396123 7.95E-07 Rv0214 7.4968379 8.3124023 7.0341622 7.4474096 8.2937944 7.8774911 6.4686333 7.7419802 7.4595382 6.9648769 7.5619527 8.276585 7.1494417 8.9108522 7.4084538 8.207783 9.9799655 6.9732524 8.7581651 9.5484941 8.7086059 8.6210244 7.4967762 10.102111 9.3296245 9.095828 9.7605316 7.8081049 9.4653562 7.7522881 10.020711 11.149624 9.2800702 10.555126 11.337877 9.7919245 8.016326 0.261529684 1.38E-05 Rv3601c 6.2786075 6.4866139 6.8435146 6.181057 7.4461907 6.0263364 6.508403 7.0120404 6.4298393 6.1699266 6.2128521 6.3353354 5.9976149 6.1597763 6.6822579 6.5863422 6.1734633 5.9370139 7.2831032 7.9948957 6.7163674 7.9177776 8.1484875 8.3650539 8.3482776 8.2202079 7.2062897 7.9046657 7.8975491 6.1059504 6.9390399 8.0021816 8.0554329 7.5051446 6.7247675 7.7839664 8.4773062 0.256489902 4.33E-08 Rv2198c 9.2065065 8.5064888 6.4155027 8.296374 7.5092836 7.2528871 10.77607 9.4275278 9.2789421 8.1517437 6.5672193 7.9058539 6.6935122 6.2754589 10.122887 6.3599007 8.9464497 6.18597 8.5010914 11.165662 8.9154972 9.2031566 9.6294888 7.6001058 9.4856845 11.393826 8.2382769 9.3291162 10.080478 11.274624 8.8713933 9.8037384 8.7281088 11.648793 8.9742668 8.7506757 9.4095968 0.253163925 0.00051299 Rv0242c 8.0613881 10.388796 9.6181397 9.8321169 11.813108 11.524138 7.2911073 9.8830863 10.906549 9.5971805 9.6958842 10.141244 9.0774726 6.5972797 9.6711266 10.069176 7.949697 10.349247 9.8401479 12.51965 10.998729 11.944063 7.8868472 10.86947 10.66911 11.399324 12.650203 11.25335 11.746973 12.78021 11.136211 12.78021 10.812603 12.10235 11.781031 11.909289 11.764286 0.252337277 5.58E-05 Rv2572c 7.8929393 5.8389698 6.145203 5.7955342 7.3372949 8.0671714 7.4400066 6.7497931 6.0701611 5.660125 5.5252968 7.8921711 8.4545508 8.3395317 7.0804854 6.1421819 7.5919402 5.9604826 6.9428703 8.2239401 8.0051793 7.7760407 8.2794656 8.7749214 8.3602048 8.3528435 8.2516087 8.1777718 8.1315436 7.9067117 7.9295084 8.7200978 8.4554076 8.1696396 7.7241847 8.2801359 9.2164675 0.250415518 2.14E-05 Rv2804c 5.8782379 5.9547963 6.4388239 6.3029923 6.740037 7.3794842 5.8292382 6.2594265 5.6567906 6.6151909 6.8764638 5.7222571 7.7870073 7.9384992 6.2951146 6.8319253 5.9362176 6.8520924 6.9389168 7.5282056 7.6874411 8.8007754 7.1162751 8.1864103 7.7343335 8.4330276 7.7251245 8.2021053 7.4289663 7.0097031 7.5459822 7.7878762 7.9252644 7.9391026 7.528989 8.1201146 7.5272584 0.249304099 2.58E-07 Rv1725c 7.0409249 7.9761689 6.8949163 7.818675 5.5469045 5.8108319 7.1472265 8.1944582 7.5521226 7.7824014 7.333382 7.0504715 5.5809189 5.7629281 8.4615178 6.1596178 7.1249958 6.0518097 8.6380468 8.3346972 7.6564465 7.9061137 7.6406669 7.9986877 8.2908016 8.1782208 9.4998947 7.7105706 7.8452473 7.6647155 8.3882946 8.1225319 8.1645966 9.553497 8.9079402 8.4077187 8.235236 0.248809581 1.02E-05 Rv3144c 6.3632227 7.3090935 6.8442563 7.1840239 7.5121578 7.7141969 6.8609231 7.0334865 7.6140158 7.8331864 7.1562257 6.3494377 7.5515983 7.383046 7.3087103 6.7740345 6.280101 7.2742547 7.7503567 9.6930826 6.7143771 9.66256 7.5001688 9.5445153 10.101356 9.1508354 7.0519284 9.5781238 10.125742 6.4087592 7.0337635 9.041696 9.8601341 7.1305415 7.1821691 7.1900395 9.6388434 0.243264737 0.00030121 Rv1270c 7.0697623 7.8814206 7.6422186 7.9700832 8.1474708 9.0516616 5.7445755 8.8505438 8.4062138 7.8887198 8.1622807 6.2623874 7.9980592 7.6305363 7.8740503 8.1309311 8.5769588 8.1764463 8.7414841 9.6863173 8.1896506 12.10235 10.251861 9.5634663 9.7269728 8.7882175 7.8506617 9.6357306 10.401416 8.1426207 7.8911749 10.047963 10.329515 8.1289363 8.3359699 8.5747547 10.320549 0.242939773 4.69E-05 Rv1967 6.2571671 6.4378532 7.053584 6.6634502 6.8193829 7.8092476 6.9003438 6.4746268 6.5728419 6.778461 6.3503337 6.5946644 7.9053585 8.2884229 6.8262677 7.8586084 6.373915 7.359882 7.5127151 10.784951 6.4849105 9.6270699 7.745514 10.579391 10.004553 8.0383499 6.5751828 9.6814159 8.4866573 6.6003761 6.5324675 8.2826244 11.353532 6.6644487 6.9851304 6.7587376 7.8315858 0.24276565 0.0020226 Rv0632c 7.1066734 6.7686946 7.7963558 6.4125428 5.4546043 5.8456335 7.6208857 8.2657181 6.7596457 6.8204727 6.6992958 7.4116117 5.9825135 5.9034512 8.0022893 7.6514666 7.8924446 7.9264868 8.5610289 7.6312812 8.6925299 7.3653139 7.1895547 7.4604483 8.8853992 9.7311726 8.9811038 9.3392879 8.3571267 7.4194177 8.0217954 7.3549242 8.2932516 8.8558222 8.2512082 8.3389519 8.8994341 0.241438894 1.35E-05 Rv2288 6.3063629 5.6927008 6.1785901 5.7468104 6.5914302 6.8967151 6.4209232 7.3458053 6.0417776 5.9006815 5.6210108 6.0312756 7.9060875 7.6955791 6.4659841 5.7817036 6.3234094 5.9841482 7.3092618 7.354068 7.7803556 7.0778728 7.8725231 7.5403747 7.7324864 7.2957317 7.822537 7.2330322 7.5330212 7.4266551 7.5649077 7.5346677 7.32894 8.1110979 7.3897636 7.9862537 7.489098 0.241100005 4.00E-07 Rv1408 6.8750429 5.7245474 6.0470636 5.8365417 5.3588573 5.6900694 7.660512 7.028151 5.7429685 6.0098609 5.7916968 7.1811317 7.1622516 6.8021386 7.8961083 6.2357122 7.2470574 6.1138438 7.8051818 7.6838363 8.6183361 7.3837387 6.6812631 7.1197009 7.1054823 6.8123472 8.6099114 7.037562 7.5789452 6.7763778 8.2698809 7.3268532 7.6350972 8.5590638 7.5798462 8.7747009 7.7376592 0.23986797 1.01E-05 Rv0258c 6.9044212 7.827023 7.7213055 7.3690015 7.2237715 7.4009334 6.6636694 7.6728244 7.3095352 8.0434103 8.2564432 6.725985 7.3965594 7.3055574 7.2257561 7.8119739 8.0758024 7.4896869 8.5599548 8.4634707 9.6204915 8.3558118 7.6845613 8.3730098 9.2147701 7.9385529 10.349821 8.3690403 8.1780105 9.8411773 9.907153 7.8714662 8.0520758 9.1802554 9.5302119 9.801818 8.1546434 0.238908859 4.96E-07 Rv2114 6.8912133 6.470406 6.5448766 6.3578113 6.2182355 6.3953288 5.7894724 6.6440762 6.7079913 7.3612603 7.0379018 6.1912108 6.5113194 7.3687467 6.0715258 6.0298457 6.7066605 6.3854338 6.0099505 7.9583024 5.9912935 9.9258553 6.1642456 9.8071096 8.7490157 12.414698 5.7832629 8.8462824 7.4270104 6.4610904 5.8850359 9.6854959 9.5225551 6.210356 6.2054874 6.1017604 7.4132365 0.23859921 0.00814781 Rv2342 6.2762676 5.9536134 6.3066479 5.8864575 8.0382644 7.4195171 6.0616795 6.2336894 5.8946729 5.931524 6.0060943 5.8295573 7.3579661 6.7585818 6.3001438 6.1423144 6.2059449 5.7727378 7.3345927 8.0782925 6.4932644 7.1454735 8.5914496 8.0740318 7.8720885 7.6838579 6.7986442 7.4263937 7.4730218 6.5084051 6.6244128 8.2361661 8.5011514 7.1977095 6.8647453 7.1115069 8.381152 0.238129506 3.58E-06 Rv3322c 6.9285338 5.3998335 5.953778 5.4883265 7.3025144 7.7185932 7.1523609 6.2568614 5.4165457 6.1022746 5.5736896 6.9336512 7.2233319 7.3004057 7.4956529 5.8532156 7.091898 6.0641846 7.4285085 7.4008146 7.6043762 7.8021601 6.6801375 7.3670689 8.0958309 6.9701142 8.6439765 8.4397289 7.8489021 7.5630312 7.7304756 7.1777765 6.9630168 8.509695 8.4488358 7.9681932 7.3242899 0.237981604 8.04E-06 Rv2728c 7.2035017 6.7470556 6.9559499 6.8189848 8.4362631 9.0578691 8.4255377 9.6756886 7.2828907 8.7200845 8.2486142 7.9407075 8.6696246 9.3289095 9.4601348 6.6986545 9.796205 7.0502718 9.5713348 10.878154 9.1740312 10.242055 7.4647172 9.2050912 9.2788164 9.1609332 9.9424713 9.9986264 9.8815712 9.9279234 9.6494495 9.747845 9.3106413 9.9011273 9.506251 9.556456 9.5757175 0.23465603 2.15E-05 Rv2023c 7.773004 5.7548473 5.9209752 5.7792318 6.3669487 6.6424857 6.8414671 7.3315974 5.8065235 6.1684558 5.9231349 7.0526744 6.0539818 6.1879354 6.6230361 6.5342748 7.1008832 6.713816 7.3985806 7.5334065 7.3555415 8.358874 7.5070843 6.7443458 8.0841752 6.821488 8.1442276 7.8809362 7.848377 7.2730267 7.8683239 6.7880731 7.6191637 7.908537 8.5243064 7.5779403 7.3918783 0.233085416 1.73E-07 Rv2202c 7.7467191 5.6749106 5.8282051 6.0083829 8.2237317 8.3805102 6.441398 7.3966221 5.8151337 5.8647554 5.8653171 7.5851024 7.1320012 7.500278 7.1497927 5.9951267 7.349761 6.0920345 7.5587022 7.2718954 7.5592095 9.7779677 7.8810825 7.7186204 7.1920041 8.2510025 9.5383449 7.0069742 7.6287723 7.2067381 8.5177139 7.5120003 6.3748097 8.5741149 7.5161515 8.5916105 9.4784789 0.230567859 0.00021243 Rv3259 6.4874586 6.6881167 6.4317907 6.7850137 7.2448451 6.0926026 6.8483356 6.073359 6.4661041 6.2778493 6.626848 6.1601438 6.1195093 6.2512173 5.7894378 6.6167299 6.1231056 6.0693744 6.8451348 7.8741744 6.32266 7.8879098 8.0882092 8.5170598 8.257601 8.0414183 6.5931666 7.948405 7.9428955 6.223808 6.6151744 7.7821793 8.0428723 7.0422585 7.1377602 7.0719366 8.351643 0.230295036 1.49E-06 Rv3277 6.565491 5.9109382 6.1156688 5.8021268 6.1864726 5.8242219 6.8603708 6.8035645 5.9788219 5.8507106 5.7462976 6.8528253 5.8699689 5.8879911 6.6445046 6.6633318 6.6641508 6.2473414 6.6675918 7.5900234 6.629311 7.5878572 6.7874733 7.6709738 7.9715126 7.168811 7.2223368 7.8109867 8.1508356 6.6795637 6.7387685 7.7043372 7.3420646 7.0974536 7.6736815 6.8550007 7.8821701 0.229873611 1.19E-08 Rv1109c 7.4124215 6.2377275 5.893762 6.0820689 7.1213229 7.4456527 7.95564 7.0658626 6.0117818 6.0588593 6.1135249 7.2445214 7.9359539 7.8734885 7.5752604 6.7122465 7.3821315 6.956575 7.3160226 8.0279817 7.8539234 9.9859649 7.0553523 9.0433923 7.7477618 9.8026672 7.4336025 8.7514009 6.8946018 7.4226899 7.5993594 10.731152 8.6761799 7.4798217 7.3503301 7.8589891 7.7571003 0.229456556 0.00017061 Rv3906c 7.9678877 6.3528925 5.4998588 6.620618 7.08646 6.6615051 7.6781266 8.3194884 6.1866632 6.2180439 6.1972031 8.0135552 7.7060655 6.6402676 8.3399459 6.3227046 7.8896093 5.9902953 7.9896649 9.4549406 8.5477773 8.1144711 6.633428 7.69688 7.7606274 7.8779376 8.0611264 8.0422606 10.479252 8.6453502 8.2186095 8.8741386 7.3358626 7.6951632 7.6351696 8.4147977 8.0542116 0.22932232 7.68E-05 Rv0440 7.5673823 8.6743843 7.6580359 8.8865878 9.0089736 7.3754723 7.9926208 7.7978768 10.328124 8.6241366 8.4741541 7.2604935 7.271521 7.6602653 8.3027289 9.2714979 10.501241 13.342173 6.8800517 7.3812957 10.567433 11.382286 7.2975502 11.488053 10.556999 13.18007 11.302883 12.978491 7.7911063 7.6124335 11.746973 9.5115063 6.6999525 9.5958504 11.82753 14.476539 10.649406 0.22852367 0.01361936 Rv2559c 7.239709 7.5869735 7.5073464 8.194183 5.7289291 6.1203456 7.0439919 8.5627114 7.7776555 7.9921982 7.7849546 7.2749867 6.1125243 6.2998395 7.8461504 7.5831344 7.8466294 7.7009701 8.1980549 9.3793072 7.5986751 8.2507077 7.7441791 9.0666482 9.2551489 8.7896892 7.9539767 11.731149 8.4186419 7.5274125 8.4040548 8.8297759 9.3585426 7.8559688 8.6210241 7.6907673 8.8252969 0.228522025 5.72E-05 Rv2484c 7.6660144 5.7439734 6.1067656 6.0295787 8.5718641 8.3316712 7.8107213 8.1613189 5.7696025 8.0170173 7.2764813 7.6868504 6.3408081 5.992306 7.2735954 6.5848616 7.827557 6.7519321 7.7700594 7.9973045 8.0932772 7.9564456 8.034999 8.0093225 8.7036819 8.3084166 9.1821368 8.3481139 7.9942898 8.2181693 8.0245848 8.1246567 8.2284238 8.9462169 8.758951 8.9182766 8.4299625 0.22685347 2.44E-05 Rv1124 6.9558531 6.3102044 6.3081809 6.2886097 7.8395272 8.8149415 7.2422745 7.6233969 6.2644089 7.4874717 7.4510128 7.1521062 8.229352 8.0768932 7.2245687 6.5141789 8.333554 6.2653352 7.9639532 7.7590273 8.2902486 9.3639893 8.0975471 8.3803353 7.5180449 9.0458489 9.7608291 8.2515586 7.1261386 7.9303016 8.9743994 9.5475135 8.0274053 9.4446038 8.7289846 9.1454186 7.5323481 0.225315387 2.00E-05 Rv1959c 6.821238 6.2903204 6.3253885 6.1909011 8.3839251 7.6095259 6.6158235 6.4993124 6.0399731 6.3072321 6.5126355 6.570944 7.039596 6.5989266 6.1901912 6.2079022 6.6416095 5.7133296 6.9811194 8.4277643 6.4539594 7.9085257 8.585406 8.6567315 8.2672413 8.1028736 6.7419361 8.1196989 7.9038065 6.997583 6.6468395 8.5121088 8.0107757 7.162816 6.9419535 6.8608476 8.9941468 0.225089443 1.77E-05 Rv0793 6.9806847 6.3023261 6.3907187 6.6425674 8.0259658 7.542901 6.3984887 6.7456206 6.136946 6.240348 6.2204565 6.5567923 7.3376776 6.7418468 6.8982798 6.4914388 6.6416095 5.8248163 7.2642999 9.0750238 6.4427159 7.6899892 8.5881255 8.9131052 8.3780127 8.3867375 6.6442048 8.2017725 8.1326452 6.7175966 6.5950795 8.9489619 8.3767992 6.9253297 6.9517999 6.7451874 9.2125063 0.22497435 6.69E-05 Rv3709c 12.577226 8.6251929 7.4640201 8.8134993 8.3319017 8.8691409 12.78021 9.0382472 7.5868681 8.6195127 9.2137321 11.864104 7.3149742 7.8366624 8.3268878 7.6562996 11.849452 6.6113503 8.9382679 11.302883 9.8937158 10.701305 7.4731978 11.732927 13.758344 10.137217 10.674293 10.446156 11.151468 10.012029 10.088233 10.822444 13.758344 9.5209739 10.588138 9.6781786 10.872467 0.224914393 0.00483437 Rv3501c 7.3025193 6.0785573 6.4860374 6.207792 7.1322838 6.0893854 6.9865755 7.4005331 6.1130354 5.7630725 5.8301007 6.8132232 6.4380643 6.0923255 7.9954463 6.7887678 7.5737467 6.6088019 7.6010697 8.118781 6.6315905 7.3542018 8.3195489 8.3380222 8.3147379 8.1438587 7.2672795 7.8340003 8.0154609 6.2321639 7.5267766 8.6340781 8.7188696 7.6579661 6.96174 7.316532 8.6229036 0.224357475 6.06E-06 Rv1197 6.8066986 6.6154225 6.4460732 6.4915294 6.3967442 6.4924839 6.506232 6.8197332 6.947426 7.0175901 7.4521271 6.3558369 6.5429676 7.9426726 6.2810488 5.8103317 6.9146684 6.3864488 6.1386005 9.4616536 7.0165866 7.3318254 6.4468087 8.6327173 8.3260297 8.621831 6.8214879 7.9417377 8.1815325 7.4119574 6.9161648 9.4084364 8.9419769 7.2675337 6.939388 7.1140454 9.0926696 0.221971869 0.00011999 Rv3107c 7.7055981 6.8916997 7.1020261 7.1761312 6.6868556 6.8777786 8.1172497 5.6049054 7.0315305 7.1353599 6.9876775 7.7077833 6.7498553 6.891253 7.1144163 7.0453747 7.6138518 7.1833195 6.0942248 7.5918756 7.7730074 8.0310907 7.5138255 10.049626 9.6015717 10.929899 7.2904428 9.4798733 7.2631445 7.5159836 7.2442736 8.3653101 9.4618509 7.0275344 6.8202598 7.3636709 11.504475 0.220159981 0.00187163 Rv0217c 7.3246171 9.6773835 6.9065112 8.7721368 6.8240777 6.1393095 7.8460607 8.216947 8.5017126 8.3268902 8.0654962 7.6244168 6.5575802 6.2856195 7.4608033 7.1280339 8.8710844 6.8392017 8.2431011 7.6882163 8.3385789 9.5991638 10.198216 10.167905 9.0309925 9.4818029 8.8185982 9.4532838 7.2177421 8.9771232 8.3506985 10.855894 9.2441805 8.8660898 8.5352157 8.3254909 7.3657012 0.218908609 0.0001941 Rv3533c 6.7320874 6.0531088 6.2687261 5.9192689 7.335569 8.179593 6.8231819 6.4400704 6.1786013 7.7850116 7.4984349 6.860454 7.4754978 7.2881156 6.4721087 6.1655988 6.5478741 5.7031999 7.5122673 8.6095349 6.811463 7.9262722 8.4873796 8.5605623 8.5664461 8.2643043 7.3414944 8.2390331 8.245884 6.5848846 6.8198414 8.6465184 8.1639389 7.086435 7.364474 7.01978 9.1321408 0.217366821 2.81E-05 Rv0270 5.5090119 6.6551386 7.0820409 7.3806853 7.6812624 7.4408594 6.2242423 7.4719108 6.7209856 7.9606031 8.2955927 6.2292272 7.5914757 7.1526388 6.9660392 7.1231381 6.4070268 7.0191146 7.6485062 7.7051153 8.1291913 8.4769483 7.4620291 7.9298979 7.8425985 7.506507 8.4660323 8.0917313 7.6649964 7.1924947 9.3103449 7.4743415 7.8371924 9.5393228 8.8521384 11.025151 7.512667 0.21664549 8.21E-05 Rv1951c 6.8523757 6.2018889 6.2202067 6.0731394 8.3017077 7.2089287 6.9140553 6.6393395 6.2524245 6.3621353 6.9812191 6.9321475 6.7650371 6.7856576 7.0082766 5.9026138 7.1503999 6.116901 7.0952164 9.1117052 6.5532164 7.7372325 8.3801253 8.8635779 8.3121065 8.3378597 6.5186098 8.1805343 8.3282102 6.8786463 6.5767725 9.1040069 8.3056865 6.6528353 7.0381474 6.6665622 9.3193861 0.216160387 0.00014913 Rv2723 6.9790277 6.2758688 6.4494359 6.5158535 8.0270041 8.0198752 6.7236277 7.2403333 6.0637449 6.5493605 7.1220471 6.8370637 8.0173751 7.997772 7.8591547 6.8998295 6.4833353 6.9196762 7.4196234 8.6307328 8.1901431 7.9014526 8.2769857 8.4484322 8.4542382 8.2353896 8.0550545 8.3240352 8.0900482 8.3320456 8.199009 8.2317593 8.100161 7.9499581 7.9599931 8.0910766 8.7261697 0.215385085 3.75E-07 Rv2678c 6.6821195 7.5851832 6.5648805 6.7354322 7.800481 7.9140522 7.1457141 6.0687364 6.8348676 6.3234473 6.2091615 7.059859 7.9510768 7.6098814 6.981629 6.1303579 6.856083 5.8955583 6.3265319 9.3071558 6.9383348 7.9354149 9.1481698 8.8284296 8.726136 8.3059596 7.3676298 7.9847492 8.079643 7.082084 6.997367 9.0944489 8.3623549 7.2809545 7.8106132 7.1693144 9.4776067 0.213793533 9.29E-05 Rv1144 7.7739312 6.2010055 6.8260497 6.4094525 6.3798057 6.8434963 7.729919 7.6406254 6.6304983 7.108401 7.2919002 8.4603435 7.0693195 7.3523245 7.4854461 6.5249425 8.1825928 6.9500851 7.8588403 9.4954952 7.2270991 8.5076259 8.7033967 9.0647919 8.7005546 8.4780218 7.6584627 8.1304885 8.5358202 7.4790978 8.2844838 9.18828 8.6593715 7.3834964 7.8490851 7.0374635 9.490021 0.213665858 7.26E-06 Rv0557 7.4232165 6.6396665 6.6452994 6.4678558 7.5401141 7.6529702 7.6464489 7.8138992 6.6439464 6.7711182 8.4479356 7.3767584 6.88782 7.4144135 7.5610945 6.9451794 7.7143988 6.4927422 8.0625802 9.8975847 7.0929256 7.8594351 8.1003492 8.9612526 9.1781684 8.8908818 6.9409302 8.5141728 9.388498 7.6696785 7.7742823 9.7355075 8.884881 7.385297 8.0711101 6.9012127 9.7986298 0.212544963 6.11E-05 Rv2369c 7.0077245 6.0908213 6.0464733 6.4518682 7.3310872 7.7084059 6.9869167 7.8945637 6.1490596 6.0142353 5.9852792 7.2389614 8.0794674 7.7709783 7.9887818 6.5015305 7.0513316 6.669743 7.7253853 8.3175308 8.0470797 7.8656795 8.3147509 8.4352932 8.5094335 7.4614731 7.5414379 8.1571149 7.8345152 9.0381746 7.6986439 8.4551877 8.1160601 7.3775716 7.5600105 7.4924062 8.8643584 0.212206523 5.06E-06 Rv0589 6.6073621 6.0801922 6.3621178 5.8515355 7.0652498 7.8681009 7.4353335 6.4453921 6.1002174 6.0871698 6.0012332 6.686885 7.6984529 7.4579719 6.0465475 6.5984017 6.1332291 6.2920639 7.7258695 8.3927338 6.4836078 7.9609366 6.7135417 8.1916373 8.629699 8.3181211 7.0110537 8.2146258 8.1962264 6.071746 6.6648849 8.249152 8.2697624 7.1934516 7.1948706 7.1009547 8.7038036 0.212153107 5.11E-05 Rv2849c 6.7229311 7.8814206 8.0516639 8.022471 7.6959633 8.1182713 6.6904118 6.6591018 6.9025007 6.7999532 7.7083846 6.2242399 8.0656025 8.6092886 8.9704751 8.2643425 7.0745779 8.4991078 8.2222998 8.2749898 8.5373507 9.8635073 7.9155019 9.2649109 8.9640556 8.5217984 9.9305641 8.8789559 8.2169454 8.0382119 9.6219698 8.5028891 8.9856195 10.068752 9.0884428 8.3402512 8.1678615 0.211576988 1.13E-05 Rv0400c 6.5526715 6.0061401 6.4003581 5.9555066 7.6793416 8.0976254 6.958109 6.9597292 6.2012241 5.9457194 6.0368393 6.9438399 8.5024358 8.4972036 7.0477205 6.2088541 7.044861 5.9966169 7.9354595 9.0546048 6.7156071 7.7944404 6.474108 9.0686928 8.6854999 8.4209965 7.2684743 8.2577628 8.3101426 6.4493076 7.0669846 8.9850539 8.5677802 7.2630102 7.4614544 7.1458651 9.3693139 0.210723878 0.00041924 Rv2808 6.1377146 6.8867832 7.3126971 6.2241144 6.5497823 7.0899921 5.8823172 6.4870827 6.559138 6.5873188 6.5652987 6.0783838 7.4405197 7.5524653 6.6088656 6.8723812 6.0381488 6.7081118 7.0905427 8.5505219 6.7784603 8.0141337 7.0419995 8.6669825 8.144468 8.3971141 7.5553327 7.8053636 7.9540568 6.1995012 7.1240701 8.6393625 8.0423131 7.2886474 6.0996431 7.6663864 8.9879913 0.210439561 2.57E-05 Rv2291 8.2514994 8.5106938 7.8285736 8.5598151 5.8665251 6.3580971 6.5045559 9.3134377 8.0435098 7.3152234 8.3136075 6.8536015 6.2507609 7.3516935 9.1400934 8.0593663 8.7649666 8.8792955 9.7084236 8.3838325 7.7383799 9.6989748 7.9163761 9.6187625 8.6279216 10.142103 8.7473845 9.1004311 7.3394505 7.6917855 8.9005889 10.170755 9.3842665 10.010876 9.0141668 10.427616 8.5439008 0.21026421 0.00034801 Rv2021c 6.6241424 6.2761505 6.4055435 6.2806502 8.1864037 7.7126629 6.2659644 7.1492878 6.2364174 6.1519553 6.3037457 6.6342802 6.9687203 6.594982 6.6186473 6.3138826 6.5889112 5.6377654 7.1972204 8.2499793 6.6103126 8.4831603 8.7372581 8.3792075 7.9050787 8.159748 6.9626559 7.7858705 7.9875904 6.6818042 6.9536453 8.1386675 7.5708294 6.9180924 6.2671534 7.3316256 8.9331482 0.210209284 3.08E-05 Rv3495c 7.8435094 5.8750463 6.1842431 6.0255898 7.9948073 7.870374 7.7377245 7.8189482 6.0566491 5.9103246 5.773126 8.1013372 8.5585983 8.6856552 7.6509705 6.0269774 7.9027522 6.1497345 7.8330625 8.4484672 7.8917437 8.0534911 8.6766436 8.8590425 8.611569 8.2875355 8.20736 8.3373561 8.3448545 7.4786826 7.8379638 8.3044036 8.1535137 8.1794727 7.5768043 8.4942966 8.8762212 0.209704323 0.00020609 Rv3184 7.310353 6.1037186 5.9505954 6.2832533 7.0081257 7.3964607 6.7703983 7.4876925 6.0389934 7.2895024 7.3099342 7.4788339 6.8523303 6.8362025 7.6407727 6.4723548 7.2652274 6.6736797 7.926423 8.6757686 8.5110091 8.4810685 7.8441503 7.8352504 7.3211894 7.6877605 7.9917674 7.4664938 8.9927142 7.789708 8.1827607 7.9766929 7.3103974 7.3171977 7.4919156 8.6232862 8.1445203 0.209684024 1.84E-07 Rv2520c 8.0858191 7.0776914 7.7536492 7.2832387 6.5157584 6.7723351 7.0659698 7.9532704 7.678732 7.7062745 7.4754035 7.8882967 7.2790008 8.4009064 7.9069639 7.4408386 8.3750335 7.6242148 7.7328139 10.100819 10.98035 9.4454931 6.9845271 8.5265724 7.8752709 7.9478375 8.5398775 8.8163161 9.70575 8.3079888 8.8688855 8.6898396 8.5980361 8.6986632 8.6695632 9.4883672 8.3809463 0.209678209 1.60E-05 Rv0389 7.1827528 6.039459 6.2567975 6.2964642 8.0238976 7.3330554 6.7649891 7.6565178 6.0688405 6.1010412 6.0029379 6.4520016 7.3331729 7.2855242 8.0269634 6.5834381 7.97059 6.7628961 7.8145651 8.0087504 9.5313067 7.5506519 7.7848986 7.7613674 8.6575046 7.2803936 7.4990177 8.1724523 8.7440675 7.4011623 7.6596607 7.7484965 8.1316337 7.9315159 7.9378274 7.9566517 7.9473553 0.209515248 6.69E-06 Rv1247c 6.5372622 6.1434676 6.3338963 6.175442 6.4051965 6.859346 6.1384929 6.9086335 6.2176705 5.7492681 5.8997663 6.3162488 7.0589977 7.2891689 7.1721836 6.5338719 6.2957651 6.2305737 7.4650275 7.7487784 7.1226477 7.5788627 6.8692732 8.0019658 7.6739637 7.5681857 7.8385254 7.1124302 7.3817818 6.5904344 7.4891916 7.6492842 8.0159378 7.5372963 6.2297934 7.9412168 8.087316 0.20947154 6.59E-08 Rv1602 6.8933109 6.984798 6.8586612 6.5624497 5.5091416 5.7856398 7.2173905 6.5633073 7.4856603 8.1805464 7.8352841 7.0893116 5.6566439 5.7917653 6.416599 5.9827144 7.580814 6.1776003 8.0048621 7.5572277 7.2020984 8.35444 6.8354347 7.5545587 7.9060027 6.6937525 9.0727502 8.3071083 7.8012694 6.9934344 7.4758054 7.2980654 7.5958159 8.7395412 8.1110384 8.0386769 7.5892598 0.209209545 4.48E-05 Rv3210c 6.0495126 7.0542621 7.2796517 7.2124076 7.052712 7.2337552 5.8524324 6.6164854 7.5532098 7.2947793 7.3940059 6.1462024 7.2245151 7.2051316 7.9066519 7.6562996 6.397931 7.3309911 7.9843926 7.3817169 7.2406169 7.9701904 6.6837678 7.9823152 8.3333702 11.81162 7.5187507 9.5993248 10.048692 6.2574588 7.1914347 8.0571455 9.1251887 8.1099447 7.2202265 8.3108196 7.482761 0.20913478 0.00122852 Rv2413c 7.7927753 5.632358 6.1949909 6.9373653 7.8653023 8.0675073 6.3648613 7.7760367 5.8751502 8.224576 7.4907322 7.2322127 7.4519428 7.5434787 7.7732441 5.7322244 7.5418754 6.1384282 8.1746324 7.8967814 9.2736163 7.3661308 8.6125338 8.2628435 8.4542998 7.9165002 8.4276216 7.8025688 7.9118223 7.9176378 8.6367752 7.7236052 8.0009774 9.0887316 8.7500234 7.4466181 8.0703017 0.209056938 3.33E-05 Rv2070c 7.6121924 6.2778469 6.860321 7.2404894 6.9678326 6.8989394 6.8786038 7.9190285 6.204255 6.9318469 6.60962 7.7923678 6.6866395 5.6959895 8.3211839 6.8380473 7.8876101 6.6075568 7.0398585 9.1861229 8.5400877 8.0440491 6.5767788 7.8743538 7.829331 7.9409012 8.0004047 7.9038442 10.239563 8.4508538 8.1013471 8.7201881 7.5249527 7.7245824 7.7502758 8.4428282 8.0293887 0.208116427 3.07E-05 Rv0476 7.3012574 6.1238809 6.0462895 5.8066225 6.7771832 6.9264524 8.0711596 5.6272462 5.9967883 5.9013788 5.8370383 7.350135 7.6878999 8.0060631 7.6448384 6.6547572 7.2184155 6.822633 6.5958381 9.7585084 6.6084572 8.2445756 6.7948787 8.586389 8.777771 8.2336227 6.6744595 8.7229933 8.4551213 6.8341539 6.7283855 9.131293 8.0255233 6.8737797 7.2366646 6.6008234 9.6209059 0.207986081 0.00114508 Rv2503c 9.0080002 6.8192997 8.1324031 6.5670397 7.7224157 8.0169043 7.7399466 7.3373318 6.5471683 8.158015 7.5112365 6.9989299 8.1545266 8.4359353 7.9376135 8.6330564 9.3014272 9.4890971 8.4199022 9.9953819 8.8496294 9.5985132 6.9156757 9.2910756 9.8058259 8.8882672 8.4432755 8.7400203 8.8746987 9.7485006 9.4118774 10.160112 10.114597 9.5294212 10.07773 7.9670787 8.8832977 0.207652154 5.49E-05 Rv1702c 6.8219227 8.3383996 6.6682918 7.9232596 7.9756591 7.1866295 6.6907732 7.5606315 6.8962324 7.2767953 7.4687206 7.0396146 6.9959514 6.3352607 7.1391375 7.1628517 6.8808878 6.8476541 7.5242569 7.9311105 9.4245386 7.2323855 7.1275461 7.9425242 7.5655956 8.1026752 10.590645 7.3224096 7.3495133 8.5082636 9.6457595 7.4707449 7.5038915 9.300779 9.0535719 9.4995843 8.3419047 0.207075619 0.0001213 Rv2502c 6.6394946 7.9741535 8.5684659 6.4271362 8.603303 7.8957422 7.1572246 8.2239646 6.9265714 6.5752103 6.4756633 7.0194347 6.641754 6.7222088 7.6566851 8.1146112 6.9693454 7.3118289 8.0949572 9.7717453 7.5859646 8.6180678 9.1937469 9.1358269 9.0126314 8.2558217 7.68982 8.6871074 8.9434613 7.2928264 8.1323001 8.9447129 8.1202634 7.7482604 8.1648497 7.4097437 9.8460676 0.206426911 2.78E-05 Rv2530c 6.803303 6.5181546 6.691543 6.5085851 5.8369768 6.1583006 6.8552683 6.8614745 6.5132482 6.8508916 6.2358028 6.8565487 6.2334394 6.9794465 7.4686964 6.6706876 6.7186447 5.8000858 7.8454911 7.9512188 6.5833916 7.8807165 8.1973684 8.0507616 8.1650066 8.1656284 7.1463746 7.8165181 7.9095485 6.4243363 7.1815881 7.7828179 7.9615162 7.057693 6.9665777 7.0500941 8.2529906 0.206333994 3.19E-07 Rv1070c 5.9227339 7.0613109 6.7495955 7.2502628 7.3727996 7.4690799 5.9396228 8.0995398 7.4721445 7.5144518 7.789461 5.8955462 7.8976933 10.02142 8.2877294 6.7618599 8.6659961 6.8064524 8.0623736 8.5242849 8.7786769 8.9806087 6.8325549 9.6027611 8.338448 8.03819 7.907883 7.9782873 7.9721722 7.614648 8.9416991 7.7277305 8.8814256 8.8564061 8.974967 12.01772 7.9115157 0.206293509 0.00112971 Rv2140c 10.14901 7.5468231 8.2529551 7.662908 7.3797155 7.6895017 7.6248906 7.5232831 8.4805358 7.6349783 7.405246 8.6336 7.6729795 8.5913969 6.8376002 7.8069222 9.8958854 8.0136371 7.0212743 9.4660814 9.6075652 9.9275889 6.5250235 10.217164 9.6190411 9.8725436 9.761231 10.134919 7.8558903 10.180142 9.3202381 10.34067 10.357409 9.4207719 8.6223555 10.244544 7.8217928 0.206082669 0.00038544 Rv0145 9.3490334 8.5899679 8.551127 8.7234645 12.78021 8.6277625 8.2345496 9.1269735 9.1202829 8.8170382 8.0825387 11.393826 7.9942483 9.1960078 7.9544692 8.2855034 10.018765 9.252856 9.7257166 11.004181 10.686571 10.864367 8.5744993 12.223228 12.060624 9.727716 10.146924 10.175428 10.509893 9.9973328 9.6329155 11.780836 12.099688 9.6168164 10.05322 10.407366 10.335503 0.204711052 0.00030779 Rv3750c 7.4899051 7.2637923 7.0751387 7.0997668 6.1330236 6.7296596 6.6788147 7.9491717 8.1900017 7.6415773 7.9272228 7.7185115 6.2404093 7.0639707 7.2465689 7.4362556 7.7545926 7.3891702 7.1678948 8.2860935 9.2209557 7.8029906 6.9010287 8.1382122 7.8498969 7.907256 9.4857915 7.5530067 7.8072533 9.0089117 9.0900578 7.8776024 8.0365893 9.183623 9.6304607 10.062473 8.2861086 0.203839172 3.64E-05 Rv0690c 6.0086155 8.3955252 7.8936759 6.1463139 8.4087737 7.9229728 6.4438813 7.8517916 6.9601318 7.5380702 7.8846593 6.3742178 7.5387431 7.1298418 6.5692189 8.0085228 7.2504229 7.4353871 7.6070965 7.3145407 7.3892228 9.9449279 6.5102292 9.5257993 7.9956503 9.1272398 8.5021043 8.8574891 7.1597933 6.9754059 8.2506255 9.0347196 8.4401791 9.2601061 8.5897868 7.6510707 12.024334 0.203593418 0.00150578 Rv2284 5.9355483 5.9384983 6.6551616 5.8828116 6.2793237 6.4580334 6.8342352 7.8290946 5.8231709 6.6594922 6.5640394 6.2373589 6.1672343 7.0806362 7.3272384 7.0787083 5.8703496 8.042163 7.7253853 7.5637669 7.2847841 8.2707496 7.6422848 7.79934 7.9834114 7.9396649 7.9249942 8.0452691 7.8346184 5.8317319 7.2063569 7.3803607 6.731166 8.1462577 7.1527939 8.0835608 7.692565 0.203588049 1.40E-05 Rv0390 9.2166313 7.5720656 7.2501698 7.5241636 8.7006926 9.0869527 6.4891407 8.893402 7.5746134 7.523643 7.8322599 7.829491 7.0328334 5.9610797 7.6060711 7.7162896 9.3000923 7.9548183 8.6090993 8.5377371 9.3664931 8.6868565 7.9649358 10.471046 8.1411529 8.8862255 9.3542855 8.2552914 9.1289975 9.0671318 9.4915758 8.4646233 9.5956343 8.6725548 10.737078 9.6391911 8.156911 0.201552144 8.47E-05 Rv3590c 7.5029275 6.8327779 6.0076329 6.4592501 7.9520505 6.4973049 7.6618806 7.1839449 6.7692938 6.4118277 6.4378192 7.376255 6.6819402 6.5214247 7.5773869 5.7891415 7.2983112 5.6848985 7.5168204 8.5863005 7.4419595 8.1667319 8.3191717 8.387454 7.8657405 7.7313973 7.0559036 8.1393513 8.5623423 7.3423609 7.3429924 8.3838236 8.0553405 6.8471608 7.128146 7.0083508 8.9424413 0.201101665 1.34E-05 Rv0914c 11.423935 9.7639059 9.1056313 8.8767191 8.6652465 7.9593116 12.223228 10.332727 9.2553006 11.919654 10.756042 11.422873 7.2295942 8.4806405 9.0723955 8.8614531 10.560292 10.452591 11.114803 11.980408 10.861416 10.835388 9.0688921 11.469255 12.978491 9.8893153 11.781748 10.612988 10.094566 12.060624 11.106452 11.357078 12.236683 11.648277 11.951014 11.669257 11.145582 0.200143278 0.00044359 Rv2002 7.6093934 5.968065 6.4463687 6.0691473 7.0073975 8.0702808 7.1783868 6.8509008 6.2580066 7.4601467 7.7303542 7.450223 8.1028796 7.7144838 6.8388302 6.6777969 7.6516381 6.4896885 8.0701848 8.2210749 7.748586 8.473949 7.5104612 8.1117657 8.6790832 8.3236452 8.6282542 8.1661492 8.0626191 7.6849342 7.6613867 7.9043646 8.283638 8.4694257 8.0778769 8.2370669 8.3395636 0.199707709 1.65E-06 RV1237 7.9886353 6.3369427 5.9189492 6.1720482 7.7477773 5.649325 7.2539905 7.6791349 6.2244398 6.0877635 6.0452313 7.9096433 6.3293409 5.4974229 7.1714753 6.5317928 7.7052069 6.5642113 7.298946 7.8939629 7.9521156 7.2975463 7.2104833 7.5643304 7.7230688 7.7924901 7.3861684 7.6382577 9.2656874 8.2094424 7.4453678 7.7775872 7.8189657 7.4928477 7.4547835 7.5758564 7.6194535 0.199304461 5.92E-05 Rv1898 7.3702816 7.487157 7.730418 7.8827366 6.452257 6.190058 6.7541547 7.7103417 6.7678424 6.3093723 7.1207523 7.4895247 6.4351216 6.126241 7.3264955 7.4888118 7.4371771 7.1267332 7.1482044 8.3016559 8.3358058 8.0556482 8.547838 8.5715701 8.1168521 8.1210216 7.9414304 7.701452 7.9649143 8.9805038 7.8256343 8.0251047 8.0638738 7.8230168 8.160436 7.7667331 8.6519853 0.198738024 2.28E-07 Rv3446c 6.8174165 7.1924478 6.2657614 7.4289715 7.3734869 7.3754723 6.9023312 7.1253758 7.1519337 6.9039287 6.5702748 6.4476922 7.0327962 6.6236377 6.4150466 6.3713123 6.1410544 6.267368 8.5167596 8.1872525 6.9764624 7.6091639 6.7037475 8.5329869 8.4032823 8.3383623 7.5227708 8.0915532 8.0337761 5.8564541 7.5056213 8.031542 8.4502428 7.7910515 7.4692351 7.5440585 8.7083193 0.19857201 7.03E-06 Rv1700 7.9738665 6.415962 5.8866802 6.3882546 6.8075512 6.5549692 6.5811774 7.8661586 6.2040086 6.0946808 6.0991305 7.9276833 7.5276268 7.6802713 7.8271271 7.1312019 8.0059301 6.5713997 7.3780546 8.8345096 8.2458186 8.0575619 6.8023641 7.975979 8.0506612 8.1442294 7.5137768 8.1228391 9.4864208 8.3846931 8.0123167 8.9229937 7.6443808 7.3955437 7.629732 7.4559607 7.941213 0.197870382 4.32E-05 Rv1411c 6.9657694 7.7324855 7.6756093 7.3021978 5.5149034 5.8593874 7.7941155 6.7028267 7.6251164 8.1797192 7.4820103 7.1566713 5.7114676 6.0183913 6.3364151 7.5668776 7.2180919 7.6947702 8.0981024 7.6397657 7.5374311 7.3334206 7.1652164 7.3770757 7.8999267 9.9603712 9.0810552 8.1895094 7.2722094 7.4268579 7.5870859 7.5955193 7.8840687 10.116895 8.4900113 8.1196 8.3398222 0.197045847 0.00030435 Rv0308 7.0944744 7.0960519 6.2281986 7.0402268 7.1257445 7.547564 6.8005411 8.1036829 6.6484665 5.4634314 5.6571117 6.9511723 7.8740493 8.0086323 7.578158 6.630977 7.0362349 6.7353941 6.9797223 9.4520358 6.8490415 7.8259005 6.3806118 9.1114191 8.9359151 8.5005652 7.0587254 8.3321498 8.354149 7.3273147 7.6066867 9.6909271 9.0402422 6.9966187 6.9419535 6.766054 9.8057463 0.196581572 0.00110637 Rv2184c 7.2130181 8.8944824 7.9657205 6.5514625 8.4707393 7.7465212 7.0010727 7.1127062 7.1821749 6.2989294 6.9091673 8.1611414 6.2024712 6.2693332 7.3686112 8.222302 7.4983017 7.4932933 8.5011358 9.5124254 7.2721223 8.0688375 9.3291114 8.9798941 9.3687333 8.4566389 7.6807916 8.4645517 8.2150168 7.4969356 7.673051 9.5808268 8.6710904 8.0152227 8.2584441 7.347124 9.4499125 0.196487387 7.85E-05 Rv3686c 7.2444754 7.7383271 7.9139309 8.0428161 5.6875915 5.5447296 7.7884609 7.7019533 8.6661711 8.1418603 7.2225951 7.510436 5.9552304 5.7434059 7.8020139 7.7399865 7.8896093 7.8976166 8.0097499 8.9252195 8.2730496 9.110572 7.4661967 7.8699812 9.1445944 7.8830426 8.6655391 9.2048242 9.392441 8.5909492 8.1225102 7.7862665 8.1509746 8.747632 8.5138476 8.3091812 7.6723266 0.195553302 0.0001513 Rv3035 6.5089905 7.5031261 6.942918 7.2391122 7.547953 7.9029398 6.9043015 7.3330682 7.466791 7.1221136 7.4611669 6.5250468 7.98155 7.5117512 6.9970593 6.997375 6.4096827 6.9696561 7.3975423 8.9713021 6.9411332 9.0182768 7.6773907 9.8600978 9.7524194 8.817673 7.1692939 8.9315469 8.5185575 6.7845094 6.8631566 8.1059471 9.3601712 7.2138333 7.3880696 7.3903534 10.110413 0.195057161 0.00045928 Rv3911 6.6440424 7.0267467 7.0047582 6.600185 7.2907968 7.7012556 7.5644633 6.7377614 6.7334506 7.111795 6.8056381 6.956223 7.57886 7.1951712 6.7845861 6.7020497 6.4586422 6.5940413 7.4617794 8.253133 7.9705864 7.5360836 7.7313732 8.2765536 8.4566995 7.9792044 8.1450182 7.9600012 8.0034138 7.9279435 7.6489592 8.0987651 7.8584169 8.0137726 7.7513481 8.0591239 8.4412121 0.194436199 7.03E-11 Rv1654 8.2969143 7.8866405 7.3784948 8.1808785 8.5481748 6.5700661 7.2845041 9.1213218 7.7261084 6.1390722 6.1449562 9.1621556 8.1508772 5.9169854 8.6893576 7.3890156 8.4152595 7.0943634 8.9588164 7.9148343 9.5243485 7.7890825 8.3550261 9.7180689 7.5603949 9.0117337 8.4870212 8.3107562 8.4641766 9.4824766 9.9095602 9.5973472 8.6555689 8.6194882 9.1474512 9.919209 7.3043796 0.193846344 0.00041621 Rv1400c 10.146766 6.4305655 6.5901582 6.5957288 8.2716844 7.5749844 7.3145511 8.0323673 6.2404135 5.4311921 5.7679218 7.4107949 6.85726 6.6103753 7.8643651 6.9598925 11.829657 6.871523 8.4158953 7.2700474 8.9491673 8.0950876 8.7133993 8.2587613 11.764286 7.651914 7.6177896 8.6852109 6.577285 7.3922086 8.8261033 6.8784871 8.8631728 8.9290434 8.524532 7.3712375 11.397864 0.192447625 0.01642773 Rv2359 7.9750726 7.2821299 6.5601153 7.7110603 7.2781814 7.5562506 5.8029322 7.9373361 9.0709028 7.8330149 7.7246025 6.8577024 7.8731396 8.0738561 7.0061656 6.7412791 8.6764922 6.8466835 6.7026314 8.615154 9.4011459 8.5232997 6.6146708 8.5225021 7.9762555 8.6816635 10.233456 7.8206927 7.6614751 8.4478265 9.3623236 8.1734984 8.7450307 9.4790314 9.6953704 9.6743588 8.215707 0.191951846 0.00038405 Rv3012c 7.4226038 6.0917631 5.9630888 5.6875561 8.2140118 7.4652267 8.1445239 6.0469063 5.8806035 8.3863326 7.3806437 7.4994964 6.4757722 6.6330261 6.4903178 5.9164398 7.2570939 6.000779 6.8092356 8.5351079 6.6739644 7.8236521 8.1698588 8.4227511 8.5769563 8.3310555 6.6332129 8.6743689 8.123337 7.2340114 6.6335259 9.3258389 8.3883678 6.6282431 7.2583917 6.6671359 9.3028349 0.191513973 0.00143351 Rv0758 6.5017296 6.6687954 6.807707 6.5078441 6.2878192 6.54865 6.4222228 7.6969925 6.9791661 7.3952741 6.9843102 6.5118352 6.5189077 7.2147676 7.1036254 6.3297089 6.2844779 6.7449883 7.6429793 7.7227897 7.741813 7.4158983 5.9350039 7.7325715 8.1269282 7.9565999 8.215855 7.8346568 7.6872584 6.8432506 7.7381327 7.7170684 7.9142945 8.5630904 7.4995286 8.2423733 7.8679187 0.190832383 5.22E-07 Rv1942c 6.3296368 7.5366619 6.924461 7.5378606 6.5579485 6.0771115 6.0030564 7.4245309 7.2918038 6.3685667 6.8828042 6.2621399 6.3630163 6.2260401 6.3895378 6.7808498 6.3120382 6.9282907 7.6038998 7.757172 7.5845983 8.1276717 7.8524978 8.1003301 7.7129917 7.9951683 7.1220475 7.3248118 7.671494 8.0583477 7.1945314 7.7291453 7.2694915 7.174939 7.1798957 7.3443282 7.9935616 0.190635289 1.36E-07 RV0687 7.8145991 6.5972826 6.5424419 6.5548456 6.2430185 6.5825015 7.6697943 6.5865492 6.8104527 7.2524563 7.5217494 7.3919817 6.3998957 7.4797054 6.2068362 6.173173 7.5109425 6.4277074 6.0351859 7.327698 8.3258775 6.9821293 7.9893592 7.5478573 9.1919025 8.4523362 8.5705647 8.0463706 6.9864734 7.9729764 8.5284092 8.028304 7.8846609 7.8827304 8.4804161 7.4105411 7.4523044 0.190625718 2.99E-05 Rv3249c 6.9390555 5.8280145 6.1512342 5.9306674 7.2781896 7.6962823 7.5726127 6.869517 6.1936669 6.2343155 6.1197347 7.0084131 7.9687628 7.2981781 6.8859878 6.1101422 6.7090049 5.6974341 7.0554349 7.0837534 6.8726188 9.456611 7.1391708 7.821196 8.6033342 7.7424181 7.6483094 8.5202338 7.6533143 6.4594562 6.89897 8.0425396 8.9707356 7.3827811 7.2302958 7.4144785 7.1418318 0.190489705 0.00020419 Rv3611 5.9335619 7.4012283 6.6798831 6.8680712 6.4179844 5.6580251 7.0720513 7.2672247 7.129884 7.8307867 7.5416803 6.367948 5.6356131 5.7445302 6.6276813 6.5515563 5.9109041 6.603076 7.238061 7.6419707 7.2084592 7.8035156 7.9332274 7.6794511 8.1627782 7.3172913 7.5736847 7.951029 7.9507107 6.3967676 7.1647959 7.1276149 7.6397201 7.7906448 7.4309968 7.9820354 7.5990922 0.190082591 1.17E-05 Rv0970 7.1873069 6.7005646 6.620289 6.9939104 7.178671 8.0293812 7.8246298 6.6312802 6.4773022 7.7191711 6.4498698 7.1102482 8.1049665 7.9981566 6.6800035 7.5413039 6.9414706 7.7732267 7.2261918 7.2763562 7.2952219 10.136689 7.2019401 9.7631317 9.3707576 9.3657927 7.1497176 9.5944407 7.0797092 7.1744849 7.3530066 10.893172 10.040862 7.2308154 7.128836 7.6763689 7.542186 0.190070097 0.00277466 Rv1524 6.2450402 8.2611324 8.0345541 7.3758207 6.6489026 6.9874765 6.4396632 7.6186707 7.3106482 8.1805541 7.7030031 6.6114282 7.0440372 7.6523515 7.6838306 7.9472129 6.9475588 7.5678214 8.2323649 8.6114072 9.1454289 8.9734703 6.5935055 8.3542224 9.010671 8.2310371 8.5491681 8.7222005 8.4356721 8.1800116 8.0961322 8.236428 8.1488787 8.7586069 8.7085006 7.7894839 8.4809388 0.189990895 2.59E-06 Rv3001c 7.2820895 6.927794 6.359556 6.6296366 6.9626099 7.0937395 7.5359774 8.1753179 6.612606 7.0844745 8.1232853 7.2782848 6.8462939 7.0726625 7.8168248 6.8046326 7.3505105 6.5209292 7.7419348 9.6307629 6.8910386 7.6661088 8.0357731 8.8461385 9.0686616 8.6323279 6.7262053 8.5893199 9.4676151 7.369182 6.9832754 9.2854703 8.7291094 6.9761219 7.6554017 6.6867493 9.6718664 0.18952026 0.00043669 Rv3029c 6.5987855 6.2518317 6.4858187 6.4941068 8.4467973 8.1177286 6.5829114 7.1376889 6.1970163 6.1476282 6.1407309 6.6438469 7.7323708 6.9510746 7.2319904 6.1091069 6.459959 6.0733283 7.9213927 7.7912645 7.5902119 7.767296 8.337876 7.7537005 7.7733678 7.6705335 7.8643919 7.5944721 7.7220717 6.9766666 7.9866615 7.6610896 7.9336955 7.4570762 7.5221431 7.4946075 7.7175421 0.188706861 1.36E-05 Rv2216 6.7724007 6.4622067 6.2816542 6.3506234 8.3031877 8.5538918 6.0090444 7.690532 6.6109622 6.4274585 7.5205449 6.4751674 8.4205662 8.1307291 7.1565269 6.5451897 7.3419755 6.9246231 8.1003973 8.2716652 7.5827609 9.0869328 7.5217826 8.0572308 8.0287291 8.4328353 7.8595337 7.768282 8.0374811 7.6926128 7.9695685 8.5090489 8.0168539 8.7959717 8.4914126 7.9062648 7.8095395 0.188467607 4.87E-05 Rv1575 6.235218 5.9161435 5.9554571 5.7923113 7.8714761 8.112205 6.9186303 6.9654249 5.9163579 5.932806 5.8541991 6.4322328 7.0493538 6.8425476 6.2375832 6.2630481 6.1119384 6.7063397 6.9440896 7.8562328 6.5680606 8.0730673 7.7330675 7.5920575 8.2343186 6.9888878 7.0523475 8.0805298 8.0677176 6.3878916 6.8109087 7.2303025 7.5247513 7.1721191 7.5383667 7.2551719 7.7429291 0.188281323 4.46E-05 Rv0427c 7.8034508 7.4753507 6.9625555 7.1874269 7.5448877 6.7168153 6.6849388 8.2254914 7.796858 7.4698717 7.6459681 7.9710084 7.3736697 6.0009993 7.443675 7.2064919 8.0818588 7.5343688 8.1508547 9.2294559 8.7880146 9.0103721 6.4567378 7.7999275 7.9935884 8.6000892 8.0271281 8.1739007 10.192115 8.7632113 8.1533596 9.0988584 8.6991362 8.1176199 8.3141501 8.5245337 7.9751714 0.187895463 1.71E-05 Rv2398c 7.9286589 6.19848 5.7495334 6.0537104 7.228984 6.8364065 7.1366392 8.1349099 6.1444155 6.1621662 6.1034635 7.9464258 7.6372561 6.9242464 8.1552997 6.2743092 7.9674539 6.1467704 7.6475863 8.2549473 8.4075597 7.6194372 7.0929769 7.6477964 7.3456974 7.4707974 7.705917 7.6550067 9.655172 8.5050948 7.8258532 8.1186997 7.3676494 7.8109693 7.5682842 8.2811248 7.9254889 0.187257753 0.00019205 Rv0251c 6.932854 7.5664272 7.6147823 7.2527043 5.6840208 6.1516955 6.8956948 9.9524656 7.484848 7.7959513 7.8653417 6.3832432 6.2874967 6.2851834 6.1850003 7.5786267 7.2306368 7.2881894 9.1126023 8.2146071 7.2272828 8.171504 6.6351294 8.7176277 8.6311926 8.1697357 7.7144372 8.3811147 8.1018273 7.1751586 8.1500971 7.9802547 8.5766963 8.2933204 9.0852322 7.9375352 8.0600134 0.187025983 0.00047263 Rv3647c 6.5276886 6.0468959 6.0566373 6.1366547 7.5678286 7.6711301 6.429446 6.5258681 6.2214782 5.7622411 6.0195446 6.6190016 7.3949918 7.7086701 7.3755013 6.3935803 6.775 6.2328926 6.9178697 7.8979876 6.8830066 7.5834913 8.3967313 7.9749245 7.5379749 8.0308167 7.2310568 7.242654 7.5866843 7.4709954 7.1289474 7.8394729 7.5552001 7.7943358 7.4740524 7.1789307 7.8291665 0.187005395 6.44E-06 Rv1846c 9.7652492 5.7331082 5.92929 6.160345 7.4254517 7.83975 8.2885924 7.0530073 5.6547229 5.9508739 6.0075822 8.3020367 7.7477241 7.8429746 7.0942823 6.1894034 8.7129599 6.1607666 7.4770261 7.7000141 8.6711107 7.1281938 6.762879 7.9791326 8.0628242 7.9900971 9.4065673 8.7250383 7.5619778 7.9955333 9.7686612 7.6979436 7.6766324 8.0360252 8.7876016 8.3686023 7.8119916 0.186705662 0.00302066 Rv0394c 6.9827983 8.0674431 8.1503646 7.8647011 7.6068548 7.9095046 8.1168082 8.3049337 7.8215017 7.9625353 7.7189051 7.0208062 5.9535751 5.7741947 8.364003 8.1435012 7.0764308 7.9029239 7.8985231 9.9424951 8.4478713 9.2048127 7.2945181 8.6356042 8.8302634 8.8220948 8.4360172 9.2595523 8.5586939 9.3426822 8.1138059 8.6990168 8.2836686 8.284822 9.0114843 7.9242678 9.2330889 0.186202001 3.01E-05 Rv2788 6.853321 7.767368 7.7512895 8.1332104 8.370278 7.1293195 6.5143772 8.5440416 6.8251709 8.3391945 8.1411559 6.8235683 7.1171868 6.7975288 7.2454465 8.2388495 8.0950417 8.0183876 8.6451792 7.6887482 7.5909122 9.6263866 9.0523041 9.2148298 9.813036 9.1853777 8.097633 8.8496379 7.4546289 7.7412511 8.7226818 10.16894 8.8993464 8.7254382 8.9621823 8.3567313 7.3125957 0.185578433 7.85E-05 Rv0474 7.4680449 7.0775898 6.0217093 7.0580418 7.7012003 6.7109951 7.2263579 7.1341829 6.76695 6.584382 6.465298 7.4381425 6.7382495 6.4484884 6.9852935 6.2468305 7.3935956 6.0827909 7.0278195 8.357403 7.8455287 7.7300291 7.9472021 8.3042792 7.8210926 7.9720296 7.4729231 7.6999309 7.9191624 7.5733751 7.8904176 8.1840773 8.1227051 7.0397812 7.4733407 7.5028612 8.4242163 0.185522282 1.65E-07 Rv1842c 7.4945815 7.8199206 7.7413619 8.2389459 6.7814737 6.065093 7.4041245 8.380552 8.1652258 8.4947879 8.4336327 7.0514101 6.3630163 6.5277243 9.3508526 8.3213279 7.3372815 7.9396167 9.3079454 10.074176 7.6477894 8.9345342 7.3656994 9.8567621 9.7050146 9.3764679 7.1102196 9.391001 9.9445197 7.4729379 7.5595072 9.6353915 9.7687028 7.3919792 7.6081317 7.1462639 10.231692 0.185342391 0.00195944 Rv0625c 7.2468973 7.3687697 7.1195149 7.4765619 6.2426194 6.6976093 7.5316606 8.0890591 7.2915739 8.8583593 8.742244 7.3234414 7.7464891 7.4765642 8.2429159 7.0683014 7.2878864 6.9659211 7.7304834 9.5570422 7.6386802 8.8651539 7.749955 8.9014746 9.276946 8.532363 7.6987162 9.4318712 9.2612184 8.2723944 7.5857514 9.39926 8.7466408 7.5781328 8.1292801 7.5621662 9.8464958 0.185320515 7.15E-05 Rv2422 7.7727951 6.0884742 5.9210165 5.9259597 5.5858468 5.9419619 8.2021924 6.3550303 5.8177601 6.0624084 5.5927339 7.6225849 6.0995522 5.9614442 8.5780146 6.4906165 7.691769 5.9180417 6.912833 7.2780891 7.5059226 8.0701306 6.4393691 7.2064208 8.192907 6.7722778 7.8145178 8.1665219 8.1200264 6.9312998 7.4659131 7.416583 6.6259192 7.5558504 7.9649351 7.3968653 7.3184987 0.185042499 0.00091311 Rv1472 6.335069 5.9938163 5.7924539 6.0698255 7.2673293 7.7941524 5.7054962 7.1693735 5.5572915 5.6888474 6.0761174 6.0772163 7.8898921 8.0826334 7.2735155 6.4335262 6.4952511 6.1530157 7.7919495 7.557498 6.8560977 8.586288 8.7471308 7.4708342 7.0833376 7.6259939 7.1277725 7.3861256 7.3506741 6.8019742 7.0325916 7.2107526 7.2025618 7.4333539 7.2938591 7.3767122 7.3900974 0.184009563 0.00022483 Rv2908c 7.1023195 6.7163086 6.1920917 6.7883789 7.3259649 5.7949685 8.0658185 7.7299376 6.5948387 7.3289516 6.6299739 7.3172417 6.5756457 6.5256319 7.0396878 6.1953721 6.8316145 5.9235673 7.2220737 7.9576894 7.8417217 8.4885072 7.6561443 7.3609098 7.9255873 6.6819198 8.2284185 8.0937967 8.1602814 7.3827301 7.7528457 7.4117737 6.9197126 8.1449249 7.9021557 8.1981972 7.7567547 0.183778603 5.70E-06 Rv2146c 7.3642645 6.3418363 6.1949909 6.0373594 7.4367817 7.1231383 7.8631726 5.6632841 6.3332439 6.2930149 7.8963988 7.4169425 6.7005994 6.6748641 5.9083298 5.9878095 7.3853629 5.9755836 5.8425859 8.3422314 6.6857605 7.6847837 6.4199789 8.3535139 8.2753207 8.5046292 6.6894504 8.2472334 8.0990367 7.5404969 6.5737801 9.3797403 8.0732623 6.4491535 7.4136572 6.6004347 9.4022174 0.18364447 0.00190786 Rv3039c 6.8209556 7.1084086 7.3270572 7.0931082 7.7877039 7.4156983 5.7890413 6.8510811 7.3543974 7.7152746 7.8131946 6.8403366 7.6727626 7.6865003 7.0115211 7.5471375 7.5070389 7.5068619 7.2810939 9.2253075 7.5609144 7.8858366 7.0289646 8.6818643 8.7140322 8.749468 7.760091 8.4350922 8.3331039 6.734612 7.94025 9.3833084 8.9868433 8.3518467 8.4268214 8.2913909 9.0903275 0.183592989 1.95E-05 Rv0842 7.338301 5.9053542 6.1274228 7.3851872 7.721419 7.3761463 7.783319 7.9468806 5.8031112 7.0904241 6.7046822 7.711804 6.7138446 6.8333149 7.6740521 6.5122302 7.2621888 7.1845097 7.2025968 8.77415 8.4360194 8.3940343 7.3320067 7.8569968 7.666508 7.6585857 7.8824902 7.9739625 9.108959 8.3779399 7.9857155 7.8490368 7.5291815 8.0410711 7.9653704 8.2560355 8.0029086 0.183181452 8.67E-06 Rv1420 6.7367907 5.9671502 6.2377126 5.9228406 8.0767656 7.9815524 7.2176221 6.9165769 6.3523032 6.122467 6.0260759 6.909765 6.9209057 6.6714029 7.1031438 5.4311921 6.6282144 5.4539337 7.5769886 8.0520673 6.5931101 8.1307672 8.5184107 7.7734098 8.390093 7.2092282 6.9339465 7.8424493 8.1859655 6.282461 6.7680205 7.6500749 7.4523621 6.9553858 6.9497381 6.9154867 8.0351084 0.183038629 0.00023287 Rv0248c 7.2581429 6.2638673 6.580919 5.9890519 7.2663051 8.2038034 6.7787055 6.7094222 6.3102936 6.9142826 7.732166 6.8618629 8.4148614 8.269184 8.6793546 6.6259068 6.7158914 6.0640317 6.6564862 8.7413155 8.2808036 8.0696482 8.5665309 8.6120846 8.636834 8.3383623 7.3954046 8.3302799 8.4871785 6.6141796 7.6672645 8.5860813 8.3285673 7.3621237 7.5843119 7.1519759 9.4914159 0.182535402 0.00044521 Rv1241 7.6906717 6.1250641 6.0505745 6.3376288 7.0016506 5.6319396 8.2883431 7.1589178 6.2085455 6.2140016 6.0442238 7.8935086 6.0855481 5.6287823 7.9735286 6.2365735 7.5050185 5.647792 6.6296102 7.5856792 7.6402625 7.7247163 7.4857689 7.4378206 8.0499916 6.9269456 8.018951 8.2070058 8.6272207 6.7053508 7.5431087 7.4989721 6.5677593 7.7430906 7.4576139 7.6725751 7.8627741 0.182201726 0.00046616 Rv0483 8.6439519 8.620336 8.560155 8.6207955 9.019563 8.779989 7.8830684 10.149821 9.6986563 7.6594887 8.0496865 9.7558819 8.9886402 5.6268556 8.2686447 9.0105494 9.1689225 8.1351502 8.3330794 9.3193597 9.1872016 10.763502 6.7235882 9.7233399 9.8037384 10.136767 10.587545 10.062226 10.989464 9.3462093 9.7065864 10.799596 9.7192027 10.913467 9.2988818 9.5813402 10.188437 0.182038296 0.00061134 Rv2671 7.1868022 8.3846313 7.8603937 8.4081658 6.104603 6.7560885 6.5920919 8.2372002 8.2931609 7.8662429 8.2320447 7.2450422 6.7460367 7.6233947 7.3747548 7.8949412 8.4891431 7.9282551 7.716173 8.4433931 9.3027924 8.318875 6.7602421 9.0335384 7.8434474 8.1820972 10.235694 7.6829779 7.4911153 8.5295966 9.8242331 8.2910866 9.1227026 9.8623239 9.6219023 9.8148678 8.1062905 0.180783073 0.00042852 RV1404 7.2124449 8.51104 8.5009532 8.2708053 7.966444 5.7125327 6.7500923 8.2431262 8.6328294 8.5413618 8.5605687 6.9204591 5.8321579 5.9206979 9.5096396 8.4309241 6.6806942 9.068908 8.3993044 10.295139 7.8871798 8.0746148 7.0202068 10.560727 10.453794 10.745343 7.3694483 13.758344 7.2494356 8.0822011 7.3802296 8.0783171 11.308075 7.5045814 7.4372925 7.6405769 7.3675657 0.180653289 0.02527516 Rv3379c 7.5731754 5.8154319 6.0412005 5.7354843 6.8345847 7.7952554 7.4610169 7.2633988 5.7986362 7.2102479 6.6245199 7.817155 7.7480628 8.0608195 7.2245412 6.4067156 7.4019495 5.9530621 7.5850028 8.6650473 6.7379303 7.8649024 8.4202364 8.9059539 8.6801087 8.4653828 7.1608841 8.1110409 8.1979766 6.4780409 6.7501541 8.6917748 8.2208849 7.0790127 7.080964 7.0583247 9.1052954 0.180598367 0.00073036 Rv1526c 6.5458638 7.9168452 7.6136389 6.8455065 7.8982413 7.6755877 7.7940877 6.9507891 7.1785048 7.0599914 7.3332323 7.3907052 6.043083 6.2775123 6.6338998 7.8537993 7.0670318 7.6325561 7.7069259 7.7631482 6.647541 10.24271 7.0484252 8.1768213 11.533374 8.408003 7.6066596 9.0742752 7.9575168 6.5772474 6.9399736 6.87253 8.0036544 7.8393825 7.4741401 8.6997973 10.572797 0.180314515 0.00463433 Rv3042c 6.317055 7.4277001 6.5043224 8.502226 7.7672138 7.2809906 6.2935788 9.722582 6.7430463 6.9479511 8.1109014 7.0717699 7.0820401 7.7868858 8.8436067 7.0901844 9.0478147 7.0210602 9.1611764 8.9577551 7.7500185 8.1944056 6.9164608 9.1633502 8.9544334 7.9553631 7.793821 8.4683934 9.7977963 7.8695199 8.9757197 8.5646953 8.9169426 8.2489764 9.5825955 7.4593788 9.4057417 0.180265349 0.00079713 Note. Fold change was defined as the log2-transformed ratio of active TB to LTBI. P values < 0.05 showed statistical significance; L, LTBI; A, active TB. Table Supplementary Table S1. Raw data of the serum reactivity against 152 Mtb antigens
Figure 1. Hierarchical clustering of differentially expressed serum biomarkers. Each column indicates one serum sample and each row indicates one Mtbantigen. Data were normalized by Z score estimation, and the difference in serum reactivity was visualized as a color spectrum. A, active TB; L, latent TB infection.
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STRING analysis was performed to investigate the interactions of 152 candidate antigens (Figure 2). Among these antigens, 13 pairs, namely, Rv2499c vs. Rv2503c, Rv2502c vs. Rv1070c, Rv0400c vs. Rv0914c, Rv2908c vs. Rv2906c, Rv0400c vs. Rv1472c, Rv0632c vs. Rv0400c, Rv0914c vs. Rv2503c, Rv0400c vs. Rv1070c, Rv0914c vs. Rv1472c, Rv0914c vs. Rv0632c, Rv0914c vs. Rv1070c, Rv3501c vs. Rv0589c, and Rv2502c vs. Rv2499c, exhibited strong associations with the highest confidence (combined score > 0.9), implying that multiple Mtb antigens may collaborate to participate in resistance to host immune responses.
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The functional classification of 152 antigens was further analyzed using the TB database (Figure 3; Supplementary Table S2, available in www.besjournal.com). These Mtb antigens were involved in various biological processes. The top three of these processes with known functions were intermediary metabolism and respiration (27.63%), cell wall and cell processes (19.74%), and lipid metabolism (11.84%). In addition, large proportions (12.50%) of the antigens were conserved hypothetical proteins whose particular functions remain unknown.
Figure 3. Functional category of candidate Mtb antigens. Analysis is based on the Sanger Institute database. N, number of antigens; PE/PPE, Pro-Glu/Pro-Pro-Glu.
Annotation Rv Number 1 intermediary metabolism and respiration Rv3841 Rv2421c Rv3324c Rv2097c Rv0187 Rv1815 Rv0062 Rv2499c Rv2716 Rv2860c Rv3601c Rv2198c Rv1408 Rv3322c Rv2728c Rv2202c Rv0793 Rv3709c Rv0217c Rv2678c Rv1144 Rv2849c Rv2291 Rv0389 Rv1602 Rv2070c Rv2140c Rv0690c Rv2284 Rv1898 Rv1654 Rv1400c RV0687 Rv1524 Rv3001c Rv3029c Rv2216 Rv0248c Rv2671 Rv3379c Rv1526c Rv3042c 2 cell wall and cell processes Rv0379 Rv1337 Rv3743c Rv3625c Rv2903c Rv2804c Rv1270c Rv2288 Rv0258c Rv3277 Rv3906c Rv2559c Rv1197 Rv3533c Rv2723 Rv3495c Rv2520c Rv0476 RV1237 Rv1411c Rv0308 Rv3035 Rv0970 Rv2398c Rv0394c Rv1842c Rv0625c Rv2146c Rv0842 Rv0483 3 conserved hypotheticals Rv3190c Rv1498A Rv3899C Rv2632c Rv1725c Rv2114 Rv2342 Rv2023c Rv3259 Rv1951c Rv2369c Rv2808 Rv2413c Rv0390 Rv3446c Rv2184c Rv3686c Rv3611 Rv2422 4 lipid metabolism Rv1483 Rv2928 Rv0214 Rv0242c Rv0632c Rv2484c Rv3107c Rv0270 Rv0557 Rv0400c Rv2503c Rv2502c Rv1070c Rv0145 Rv0914c Rv2002 Rv1472 Rv3039c 5 virulence, detoxification, adaptation Rv2031c Rv0597c RV2026C Rv1967 Rv0440 Rv1124 Rv1959c Rv3501c Rv0589 Rv1247c Rv2530c Rv1942c Rv0251c Rv1241 6 information pathways Rv2906c Rv3297 Rv0861c Rv2572c Rv1109c Rv3210c Rv1700 Rv3911 Rv3012c Rv0427c Rv3647c Rv2908c Rv1420 7 regulatory proteins Rv1474c Rv0494 Rv2021c Rv2359 Rv0758 Rv3249c Rv1846c Rv2788 Rv0474 RV1404 8 insertion seqs and phages Rv3184 Rv1702c Rv3750c Rv1575 9 PE/PPE Rv3144c Rv3590c Note. Annotations are according to Sanger Institute database (http://tuberculist.epfl.ch/). Table Supplementary Table S2. Functional Classification of 152 Mtb Antigens
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To validate the potential capability of candidate antigens for discriminating LTBI from active TB, 11 antigens that had high fold-change values and could easily be expressed and purified were selected and further assessed by ELISA using 279 serum samples including 94 healthy controls, 93 LTBI patients, and 92 active TB patients. As expected, the 11 antigen-specific IgG levels were significantly higher in active TB patients than in LTBI individuals, which is consistent with microarray results (Figure 4).
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The performance of 11 antigens in distinguishing between LTBI and active TB was evaluated using ROC curves, and their AUCs, specificities, and sensitivities were calculated (Table 2). Results showed that Rv2031c, Rv1408, and Rv2421c had higher AUC of 0.8520 (95% CI: 0.7954-0.9086), 0.8152 (95% CI: 0.7494-0.8809) and 0.7970 (95% CI: 0.7271-0.8668), respectively. Several other antigens, including Rv2716, Rv2002, Rv2097c, Rv0248c, Rv2026c, Rv0389, Rv2906c, and Rv2928, also distinguished between LTBI and active TB, and the results were statistically significant (P < 0.05).
Rv Number Gene Name AUC (95% CI) PValue Sensitivity (%, 95% CI) Specificity (%, 95% CI) Rv2031c hspX 0.8520 (0.7954-0.9086) < 0.0001 75.00 (64.89-83.45) 84.95 (76.03-91.52) Rv1408 rpe 0.8152 (0.7494-0.8809) < 0.0001 75.00 (64.89-83.45) 87.10 (78.55-93.15) Rv2421c nadD 0.7970 (0.7270-0.8668) < 0.0001 77.17 (67.25-85.28) 82.80 (73.57-89.83) Rv2716 Rv2716 0.7931 (0.7212-0.8650) < 0.0001 66.30 (55.70-75.83) 97.85 (92.45-99.74) Rv2002 fabG3 0.7765 (0.7047-0.8484) < 0.0001 73.91 (63.71-82.52) 83.87 (74.80-90.68) Rv2097c Rv2097c 0.7184 (0.6415-0.7954) < 0.0001 60.87 (50.14-70.88) 80.65 (71.15-88.11) Rv0248c Rv0248c 0.7176 (0.6395-0.7956) < 0.0001 69.57 (59.10-78.73) 73.12 (62.92-81.79) Rv2026c Rv2026c 0.7010 (0.6237-0.7782) < 0.0001 67.39 (56.82-76.80) 69.89 (59.50-78.97) Rv0389 purT 0.7021 (0.6254-0.7789) < 0.0001 58.70 (47.95-68.87) 82.80 (73.57-89.83) Rv2906c trmD 0.6605 (0.5781-0.7430) 0.0002 52.17 (41.50-62.70) 89.25 (81.11-94.72) Rv2928 tesA 0.6584 (0.5760-0.7409) 0.0002 42.39 (32.15-53.14) 92.47 (85.11-96.92) Note. 95% CI: 95% confidence interval. Table 2. AUCs for Discriminating between LTBI and Active TB Patients
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According to AUC values, we selected the top three antigens, namely Rv2031c, Rv1408, and Rv2421c to perform antigen combination analysis. Our results showed that the positive rate of antigen combination in the LTBI group (namely, specificity) was increased to 93.6%, which is higher than that obtained for any single antigen (Figure 5A). There was a statistically significant difference in the detection rate of Rv2421c vs. combination (P = 0.002), and Rv2031c vs. combination (P = 0.039). The positive rate of antigen combination in the active TB group (namely, sensitivity) was increased to 81.5%, which was slightly higher than that observed for each antigen, although it was not statistically significant (Figure 5B). In addition, the positive rate of each antigen did not show any statistical difference with respect to the LTBI or the active TB group.
Figure 5. Distribution of positive and negative responders to Rv2031c, Rv1408, Rv2421c antigens, and a combination of these antigens. (A) Latent TB infection group. (B) Active tuberculosis group. For antigen combinations, a positive responder was determined if any two antigens yielded a positive result. Detection rates were compared using McNemar's test.
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Logistic regression analysis was used to enhance diagnostic ability. Our results showed that Rv1408, R0248, Rv2026c, Rv2716, Rv2031c, Rv2928, and Rv2121c were the major predictive antigens for differentiating between LTBI and active TB patients. Therefore, a regression model Logit P = -6.28 + 16.92 × Rv1408 - 11.26 × R0248 + 19.82 × Rv2026c + 25.49 × Rv2716 + 11.35 × Rv2031c - 23.07 × Rv2928 + 11.55 × Rv2121c was established. In the training set, the AUC of the model was 0.9844 (95% CI: 96.62%- 1.003%), with sensitivity and specificity of 96.77% (95% CI: 88.83%-99.61%) and 93.75% (95% CI: 84.76%-98.27%), respectively (Figure 6A). In the validation set, the AUC of the model was 0.9632 (95% CI: 91.40%-1.012%), with sensitivity and specificity of 93.33% (95% CI: 77.93%-99.18%) and 93.1% (95% CI: 77.23%-99.15%), respectively (Figure 6B).