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Table 1 Significant associations between genomic variants and drug resistance phenotypes identified by PhyC

From: Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance

Locus Known Phenotype Association [13] Lineage Observed Phenotype Association (position; p-value) Total
rpoB RMP 2 INH(761,155;1.2 × 10− 06, 761,139;5.6 × 10− 06), MDR(761,155;1.5 × 10− 12, 761,139;1.4 × 10− 07, 761,140;5.5 × 10− 04), RMP(761,155;2.4 × 10− 11, 761,139;6.7 × 10− 09, 761,110;4.6 × 10− 04, 761,140;9.3 × 10− 04), XDR(761,155;2.6 × 10− 04, 761,139;7.5 × 10− 04) 11
rpoB RMP 4 AG(761,155;2.0 × 10−5), EMB(761,155;2.2 × 10− 14), INH(761,155;3.4 × 10− 32, 761,139;6.2 × 10− 11, 761,110;7.6 × 10− 08, 761,140;3.3 × 10− 07), MDR(761,155;2.1 × 10− 45, 761,139;2.8 × 10− 20, 761,140;1.3 × 10− 09, 761,110;1 × 10− 08, 759,939;2.8 × 10− 04), PZA(761,155;1.5 × 10− 12, 761,110;2.2 × 10− 06), RMP(761,155;5.7 × 10− 54, 761,139;9.7 × 10− 27, 761,110;2.6 × 10− 12, 761,140;3.4 × 10− 11, 761,998;1.1 × 10− 05, 761,109;7.3 × 10− 05, 759,939;4.9 × 10− 04), STRx10P(761,155;2.1 × 10− 16, 761,110;7.5 × 10− 04), XDR(761,155;7.1 × 10− 14, 761,110;2.7 × 10− 05) 23
rpoB RMP 2 + 4 AG(761,155;2.3 × 10−5), EMB(761,155;3.8 × 10− 18, 761,140;6.3 × 10− 06, 761,110;1.1 × 10− 05, 761,139;2 × 10− 05), INH(761,155;2.3 × 10− 42, 761,139;3.5 × 10− 19, 761,140;2.3 × 10− 11, 761,110;1.1 × 10− 09, 761,161;1.5 × 10− 06), MDR(761,155;7.8 × 10− 63, 761,139;1.7 × 10− 31, 761,140;4.8 × 10− 15, 761,110;1.3 × 10− 13, 761,161;5.8 × 10− 05, 761,095;1.8 × 10− 04, 759,939;2.6 × 10− 04, 761,109;2.6 × 10− 04), PZA(761,155;5.6 × 10− 16, 761,110;2 × 10− 07, 761,139;5.8 × 10− 04), RMP(761,155;3.5 × 10− 70, 761,139;3.2 × 10− 38, 761,110;2.4 × 10− 17, 761,140;2.2 × 10− 15, 761,161;4.4 × 10− 07, 761,109;3.5 × 10− 05, 761,998;1 × 10− 04, 761,095;3.1 × 10− 04, 759,939;4.7 × 10− 04, 760,314;4.7 × 10− 04), STM(761,155;8.4 × 10− 21, 761,110;2.1 × 10− 07, 761,139;2.6 × 10− 07, 761,140;8.5 × 10− 05, 761,161;1.8 × 10− 04), XDR(761,155;2.2 × 10− 18, 761,110;2.6 × 10− 08, 761,139;9.7 × 10− 08, 761,161;1.9 × 10− 06, 761,109;6.2 × 10− 05) 40
embB EMB 2 EMB(4,247,429;3 × 10− 07, 4,247,431;1.8 × 10− 04), INH(4,247,429;9.3 × 10− 10, 4,247,431;3.1 × 10–05), MDR(4,247,429;2.5 × 10− 08, 4,247,431;1.1 × 10− 04), RMP(4,247,429;7.6 × 10− 09, 4,247,431;1.3 × 10− 04, 4,247,730;8.7 × 10− 04), STM(4,247,429;1 × 10− 05, 4,247,431;1.1 × 10− 04), XDR(4,247,429;4.3 × 10− 06, 4,247,431;1.2 × 10− 04, 4,247,730;1.2 × 10− 04) 14
embB EMB 4 AG(4,247,431;7.1 × 10− 4), EMB(4,247,431;3 × 10− 11, 4,247,729;3 × 10− 08, 4,247,730;1 × 10− 07, 4,248,003;1 × 10− 07, 4,247,429;1.5 × 10− 06, 4,247,574;8.1 × 10− 04), INH(4,247,431;6.6 × 10− 19, 4,247,730;1.4 × 10− 09, 4,247,429;1.7 × 10− 09, 4,247,729;6.3 × 10− 06, 4,247,574;1.8 × 10− 05, 4,248,003;2.8 × 10− 05), MDR(4,247,431;2.3 × 10− 21, 4,247,429;1.5 × 10− 09, 4,247,730;8.8 × 10− 08, 4,247,574;6 × 10− 07, 4,247,729;4.2 × 10− 06, 4,248,003;6 × 10− 04), PZA(4,247,431;1.2 × 10− 04, 4,247,730;2.2 × 10− 04, 4,248,003;5.3 × 10− 04), RMP(4,247,431;2.2 × 10− 18, 4,247,429;1.5 × 10− 10, 4,247,730;1.4 × 10− 08, 4,247,574;6.6 × 10− 05, 4,247,729;1.3 × 10− 04, 4,248,003;1.5 × 10− 04), STM(4,247,431;1.5 × 10− 08, 4,247,729;3.6 × 10− 06, 4,247,574;7.2 × 10–04), XDR(4,247,429;1.3 × 10− 04) 31
embB EMB 2 + 4 AG(4,247,431;3.5 × 10−4), EMB(4,247,429;9.2 × 10−21, 4,247,431;1.5 × 10− 16, 4,247,729;2.1 × 10− 09, 4,247,730;6.4 × 10− 08, 4,248,003;2.8 × 10− 07, 4,247,574;1.4 × 10− 04, 4,249,518;1.9 × 10− 04), FQ(4,247,730;9.5 × 10− 07), INH(4,247,429;2.7 × 10− 27, 4,247,431;1 × 10− 25, 4,247,730;8.4 × 10− 14, 4,248,003;1.2 × 10− 08, 4,247,729;1.4 × 10− 07, 4,247,574;1.7 × 10− 07), MDR(4,247,431;3.2 × 10− 26, 4,247,429;6.1 × 10− 26, 4,247,730;2 × 10− 12, 4,247,574;2.5 × 10− 09, 4,247,729;1.3 × 10− 07, 4,248,003;1.5 × 10− 07), PZA(4,247,730;6.3 × 10− 08, 4,247,431;2 × 10− 05, 4,247,429;2.9 × 10− 04, 4,248,003;4.6 × 10− 04), RMP(4,247,429;4.1 × 10− 29, 4,247,431;4.8 × 10− 24, 4,247,730;3.1 × 10− 13, 4,248,003;3.5 × 10− 07, 4,247,574;4.7 × 10− 07, 4,247,729;2.5 × 10− 06, 4,247,469;4.7 × 10− 04), STRx10P(4,247,431;2.2 × 10− 14, 4,247,429;2.9 × 10− 13, 4,247,729;1.4 × 10− 05, 4,248,003;2.6 × 10− 05, 4,247,730;5.5 × 10− 05, 4,247,574;6.9 × 10− 05), XDR(4,247,429;4.4 × 10− 13, 4,247,431;8.9 × 10− 10, 4,247,730;2.6 × 10− 08) 41
katG INH 2 INH(2,155,168;2.7 × 10− 07), MDR(2,155,168;4.5 × 10− 08), RMP(2,155,168;5.7 × 10− 04), STM(2,155,168;8.3 × 10− 04), XDR(2,155,168;4.1 × 10− 09) 5
katG INH 4 EMB(2,155,168;1.5 × 10− 07), INH(2,155,168;2 × 10− 63, 2,155,167;8.5 × 10− 05), MDR(2,155,168;3 × 10− 58, 2,155,167;2.8 × 10− 04), PZA(2,155,168;1.5 × 10− 09), RMP(2,155,168;2.9 × 10− 29), STRx10P(2,155,168;2.8 × 10− 11), XDR(2,155,168;1.8 × 10− 14) 9
katG INH 2 + 4 EMB(2,155,168;4.8 × 10− 11), INH(2,155,168;7.1 × 10− 72, 2,155,167;1.1 × 10− 04), MDR(2,155,168;3.3 × 10− 68, 2,155,167;2.6 × 10− 04), PZA(2,155,168;1.7 × 10− 11), RMP(2,155,168;2.5 × 10− 36), STRx10P(2,155,168;3.9 × 10− 18), XDR(2,155,168;3.5 × 10− 28) 9
rpsL STM 2 INH(781,687;5.9 × 10− 05), MDR(781,687;5.3 × 10− 05), RMP(781,687;4.8 × 10− 04), STM(781,687;4.1 × 10− 08) 4
rpsL STM 4 AG(781,687;3.8 × 10− 4), INH(781,687;4.3 × 10− 15), MDR(781,687;3.9 × 10− 12), PZA(781,687;6.1 × 10− 06), RMP(781,687;8.3 × 10− 10), STM(781,687;9.6 × 10− 14, 781,822;2.3 × 10− 04) 6
rpsL STM 2 + 4 AG(781,687;3.8 × 10− 5), EMB(781,687;3.5 × 10− 05), FQ(781,687;8.3 × 10− 05), INH(781,687;2.3 × 10− 26, 781,822;6.4 × 10− 05), MDR(781,687;2.3 × 10− 25, 781,822;4.1 × 10− 06), PZA(781,687;1.5 × 10− 08), RMP(781,687;4.8 × 10− 22, 781,822;8.6 × 10− 06), STM(781,687;3.4 × 10− 30, 781,822;2.6 × 10− 07), XDR(781,687;4.3 × 10− 09) 13
Rv1482c-fabG1 INH, ETH 2 INH(1,673,425;9 × 10− 06), MDR(1,673,425;5.7 × 10− 05) 2
Rv1482c-fabG1 INH, ETH 4 INH(1,673,425;2.2 × 10− 20), MDR(1,673,425;2 × 10− 07), XDR(1,673,425;3.9 × 10− 05) 3
Rv1482c-fabG1 INH, ETH 2 + 4 EMB(1,673,432;5.4 × 10− 05), ETH(1,673,425;7.6 × 10− 04), FQ(1,673,432;9 × 10− 04), INH(1,673,425;6.4 × 10− 27, 1,673,432;8.3 × 10− 07), MDR(1,673,425;4.4 × 10− 14, 1,673,432;6.4 × 10− 05), RMP(1,673,432;7.9 × 10− 06, 1,673,425;3 × 10− 05), STEP(1,673,432;8.5 × 10− 05, 1,673,425;3.6 × 10− 04), XDR(1,673,425;8.7 × 10− 06, 1,673,432;1.2 × 10− 05) 14
gyrA FQ 2 EMB(7582;1.3 × 10− 05), ETH(7582;9.5 × 10− 04), FQ(7582;2.3 × 10− 09, 7570;7.6 × 10–06, 7581;4.1 × 10− 04), INH(7582;9.9 × 10− 06), MDR(7582;7.9 × 10− 05), OFL(7582;1.4 × 10− 06, 7570;8.5 × 10− 04, 7581;8.5 × 10− 04), RMP(7582;2.6 × 10− 06, 7570;1.2 × 10− 04, 7581;9.3 × 10− 04), STM(7582;6.5 × 10− 04), XDRvMDR(7570;9.6 × 10− 04), XDR(7570;5.7 × 10− 07, 7582;7.5 × 10− 07, 7581;7.5 × 10− 04) 21
gyrA FQ 4 EMB(7570;1.2 × 10− 05), FQ(7570;1.9 × 10− 08, 7582;3 × 10− 06, 7581;2.1 × 10− 05), INH(7570;3.2 × 10− 10, 7581;9.2 × 10− 05, 7582;1.1 × 10− 04), KAN(7570;1.5 × 10− 04), MDR(7570;1 × 10− 08, 7582;4.2 × 10− 06, 7581;5 × 10− 05), OFL(7570;2.5 × 10− 04, 7582;5.6 × 10− 04), PZA(7570;1 × 10− 05, 7581;1.3 × 10− 04), RMP(7570;3.4 × 10− 11, 7582;5 × 10− 08, 7581;5.1 × 10− 06), XDR(7570;3.3 × 10− 10, 7582;2.7 × 10− 05, 7572;3.6 × 10− 04) 24
gyrA FQ 2 + 4 AMK(7570;6.5 × 10− 04), CAP(7570;9.9 × 10− 04), EMB(7582;4.2 × 10− 13, 7570;1.1 × 10− 08, 7572;3.7 × 10− 04, 7581;4.8 × 10− 04), ETH(7582;1.3 × 10− 04), FQ(7582;3.6 × 10− 18, 7570;4.1 × 10− 14, 7581;2.4 × 10− 09, 7572;6.1 × 10− 04), INH(7582;4.5 × 10− 15, 7570;4.2 × 10− 14, 7581;1.2 × 10− 08, 7572;8.3 × 10− 06), KAN(7570;5.7 × 10− 06, 7572;6.7 × 10− 05), MDR(7582;2.2 × 10− 15, 7570;1.8 × 10− 11, 7581;6.4 × 10− 07), OFL(7582;1.3 × 10–10, 7570;2 × 10–07, 7581;5.8 × 10− 06), PZA(7581;1.2 × 10− 07, 7570;2.4 × 10− 07, 7572;9.7 × 10− 05, 7582;4.6 × 10− 04), RMP(7582;2.3 × 10− 20, 7570;2.5 × 10− 17, 7581;1.8 × 10–10, 7572;1 × 10− 06), STM(7582;1.9 × 10− 10, 7570;1.5 × 10− 06, 7581;1.8 × 10− 04), XDRvMDR(7570;4.2 × 10− 05, 7582;5.7 × 10− 04), XDR(7570;3.4 × 10− 19, 7582;3 × 10− 16, 7572;9.7 × 10− 08, 7581;2.9 × 10− 07) 44
rrs STM, AG 2 AMK(1,473,246;1.8 × 10− 04), CAP(1,473,246;5 × 10− 08), INH(1,473,246;5 × 10− 06), KAN(1,473,246;1.3 × 10− 11), RMP(1,473,246;8.9 × 10− 06), STM(1,473,246;4.1 × 10− 04), XDRvMDR(1,473,246;3.6 × 10− 05), XDR(1,473,246;7.4 × 10− 11) 8
rrs STM, AG 4 AG(1,473,246;2.6 × 10−7), AMK(1,473,246;4.6 × 10− 06), CAP(1,473,246;2 × 10− 06), CIP(1,473,246;9.4 × 10− 04), EMB(1,473,246;7.1 × 10− 07), FQ(1,473,246;2.5 × 10− 04), INH(1,473,246;3.2 × 10− 10), KAN(1,473,246;3.3 × 10− 10), MDR(1,473,246;4.6 × 10− 06), PZA(1,473,246;9.4 × 10− 10), RMP(1,473,246;1.9 × 10− 16), STM(1,473,246;3.1 × 10− 05, 1,472,359;2.3 × 10− 04), XDRvMDR(1,473,246;1.9 × 10− 05), XDR(1,473,246;1.6 × 10− 13) 15
rrs STM, AG 2 + 4 AG(1,473,246;7.5 × 10−5), AMK(1,473,246;3.9 × 10− 11), CAP(1,473,246;7.2 × 10− 14), CIP(1,473,246;6.5 × 10− 04), EMB(1,473,246;2.5 × 10− 11), FQ(1,473,246;3.5 × 10− 07), INH(1,473,246;3.6 × 10− 20, 1,472,359;1.2 × 10− 05), KAN(1,473,246;7.9 × 10− 22), MDR(1,473,246;1.8 × 10− 11, 1,472,359;4.4 × 10− 04), PZA(1,473,246;2.6 × 10− 10), RMP(1,473,246;7.3 × 10− 26), STM(1,473,246;1.3 × 10− 11, 1,472,359;1.5 × 10− 08), XDRvMDR(1,473,246;2.1 × 10− 09), XDR(1,473,246;7.9 × 10− 29, 1,472,359;1.5 × 10− 04) 18
thyX-hsdS.1 PAS 2 XDR(3,067,961;7.5 × 10−04) 1
thyX-hsdS.1 PAS 4 INH(3,067,961;4.9 × 10−04), STM(3,067,961;3.2 × 10− 04) 2
thyX-hsdS.1 PAS 2 + 4 EMB(3,067,961;1 × 10− 05), INH(3,067,961;1.4 × 10− 07), MDR(3,067,961;6.4 × 10− 05), RMP(3,067,961;9.4 × 10− 05), STM(3,067,961;2.3 × 10− 07), XDR(3,067,961;1.2 × 10− 05) 6
rpoC RMP 4 EMB(764,817;2 × 10− 04), MDR(764,817;6 × 10− 07, 764,840;2.8 × 10− 04), PZA(764,817;8.3 × 10− 08), RMP(764,817;3.6 × 10− 08, 764,840;4.9 × 10− 04, 767,123;4.9 × 10− 04), STM(764,817;3.4 × 10− 04) 8
rpoC RMP 2 + 4 EMB(764,817;1.9 × 10− 04), INH(764,817;1.1 × 10− 05, 764,840;1.1 × 10− 04), MDR(764,817;4.9 × 10− 10, 764,840;9.7 × 10− 06), PZA(764,817;2 × 10− 07), RMP(764,817;1.4 × 10− 09, 764,840;2.2 × 10− 05, 764,363;4.7 × 10− 04, 767,123;4.7 × 10− 04), STM(764,817;3.8 × 10− 06) 11
embC-embA EMB 2 EMB(4,243,217;1.7 × 10−04) 1
embC-embA EMB 4 EMB(4,243,221;3.7 × 10−04, 4,243,190;3.8 × 10–04), INH(4,243,221;8.5 × 10− 05), MDR(4,243,217;4.6 × 10− 06, 4,243,221;4.6 × 10− 06, 4,243,190;3.6 × 10− 05), RMP(4,243,221;1.1 × 10− 05, 4,243,190;4.9 × 10− 04) 8
embC-embA EMB 2 + 4 EMB(4,243,217;1.4 × 10−07, 4,243,190;3 × 10− 07, 4,243,221;1.3 × 10− 06), INH(4,243,217;4 × 10− 08, 4,243,221;2.3 × 10− 06, 4,243,190;3 × 10− 05), MDR(4,243,217;1.2 × 10− 09, 4,243,221;6.9 × 10− 08, 4,243,190;1.9 × 10− 06), RMP(4,243,221;2.2 × 10− 07, 4,243,217;6.1 × 10− 07, 4,243,190;4.8 × 10− 06), STM(4,243,217;8.6 × 10− 04) 13
hadA Novel 4 INH(732,110;4 × 10−04), MDR(732,110;2.8 × 10− 04) 2
hadA Novel 2 + 4 INH(732,110;1.1 × 10−04), MDR(732,110;2.6 × 10− 04), STM(732,110;4 × 10− 04) 3
pncA PZA 4 EMB(2,288,868;3.8 × 10− 04), MDR(2,288,764;2.8 × 10− 04), RMP(2,288,764;4.9 × 10− 04) 3
pncA PZA 2 + 4 EMB(2,288,820;1.9 × 10− 04, 2,289,103;1.9 × 10− 04), MDR(2,289,207;2.6 × 10− 04), PZA(2,289,207;9.7 × 10− 05), RMP(2,288,778;4.7 × 10− 04, 2,288,820;4.7 × 10− 04) 6
pncA-Rv2044c PZA 4 RMP(2,289,252;4.9 × 10− 04), XDR(2,289,252;3.6 × 10− 04) 2
pncA-Rv2044c PZA 2 + 4 INH(2,289,252;1.1 × 10− 04), MDR(2,289,252;5 × 10− 05), PZA(2,289,252;2 × 10− 07), RMP(2,289,252;4.8 × 10− 06), XDR(2,289,252;6.2 × 10− 05) 5
Rv3115-moeB2 Novel 2 + 4 MDR(3,482,717;6.7 × 10− 04), STM(3,482,717;6.7 × 10− 04) 2
eis-Rv2417c AG 2 + 4 EMB(2,715,342;1.6 × 10− 05), FQ(2,715,342;1.7 × 10− 04), INH(2,715,342;1.1 × 10− 04), KAN(2,715,342;5.4 × 10− 04), RMP(2,715,342;2.2 × 10− 05), STM(2,715,342;1.4 × 10− 05) 7
folC PAS 4 EMB(2,747,471;3.8 × 10−04) 1
folC PAS 2 + 4 EMB(2,747,471;3.7 × 10−04), INH(2,747,471;1.1 × 10− 04), STM(2,747,471;4 × 10− 04) 3
whiB6-Rv3863 Putative STM or ETH 2 + 4 EMB(4,338,594;9 × 10− 04) 1
fabG1 INH [53] 4 INH(1,674,048;6.3 × 10− 06) 1
fabG1 INH [53] 2 + 4 INH(1,674,048;5.5 × 10− 06) 1
oxyR’-ahpC INH 2 + 4 INH(2,726,141;6.8 × 10− 04), PZA(2,726,141;9 × 10− 04) 2
gyrB FQ 4 RMP(6620;4.9 × 10− 04) 1
gyrB FQ 2 + 4 RMP(6620;4.7 × 10−04) 1
  1. (p-values < 1E-3) Drug resistance phenotype abbreviations are as given in methods. ‘Total’ refers to the total number of significantly associated variants for the locus and lineage in question. AMK = Amikacin-resistance, AG = Aminoglycoside-resistance, CAP = Capreomycin-resistance, CIP = Ciprofloxacin-resistance, EMB = Ethambutol-resistance, ETH = Ethionamide-resistance, FQ = Fluoroquinolone-resistance, INH = Isoniazid-resistance, KAN = Kanamycin-resistance, MDR = Multidrug-resistant, OFL = Ofloxacin-resistance, PAN = pan-susceptible (no known drug-resistance), PZA = Pyrazinamide-resistance, RMP = Rifampicin-resistance, STM = Streptomycin-resistance, XDR = Extensively drug-resistant