This tool processes raw sequence data to infer strain type and identify known drug resistance markers.
Single nucleotide polymorphisms (SNPs) in coding regions are annotated using the reference amino acid, codon number and alternative amino acid (e.g. Ser315Thr in katG).
SNPs in non-coding regions (i.e. RNA genes and intergenic regions) are annotated using the reference nucleotide, gene coordinate and alternative nucleotide (e.g. A1401G in rrs or C-37A in eis promoter).
Indels are annotated using the reference VCF allele, gene coordinate and alternative VCF allele (e.g. T902TA insertion in katG).
Drug1 | Resistance | Supporting Mutations |
Isoniazid | R | fabG1 (C-15T promoter), kasA (Gly312Ser) |
Rifampicin | R | rpoB (His445Asp) |
Ethambutol | | |
Pyrazinamide | | |
Streptomycin | | |
Ethionamide | R | fabG1 (C-15T promoter) |
Fluoroquinolones | | |
Amikacin | | |
Capreomycin | | |
Kanamycin | | |
Para-aminosalisylic_acid | | |
Linezolid | | |
Clofazimine | | |
Bedaquiline | | |
Multi drug resistance | R | |
Extremely drug resistance | | |
Lineage2 | Name | Main Spoligotype | RDS |
lineage1 | Indo-Oceanic | EAI | RD239 |
lineage1.2.1 | Indo-Oceanic | EAI2 | RD239 |
Mutations in candidate genes:
Gene | Chromosome Position | Mutation | Lineage |
gyrB | 5616 | Indel: CGG/CG | |
gyrB | 6112 | Met291Ile | |
gyrA | 7362 | Glu21Gln | |
gyrA | 7585 | Ser95Thr | |
gyrA | 7929 | Indel: GCC/GC | |
gyrA | 8452 | Ala384Val | |
gyrA | 8659 | Indel: AC/A | |
gyrA | 9143 | Ile614Ile | |
gyrA | 9260 | Leu653Leu | |
gyrA | 9304 | Gly668Asp | |
gyrA | 9368 | Indel: GC/G | |
gyrA | 9501 | Indel: CG/C | |
rpoB | 760078 | Indel: AGG/AG | |
rpoB | 760477 | Indel: GCC/GC | |
rpoB | 761139 | His445Asp | |
rpoB | 761482 | Indel: CGGG/CGG | |
rpoB | 761559 | Indel: ACC/AC | |
rpoB | 762665 | Indel: GCCC/GC | |
rpoB | 763031 | Ala1075Ala | |
rpoB | 763183 | Indel: GCC/GC | |
rpoC | 763884 | Ala172Val | |
rpoC | 763886 | Arg173Arg | |
rpoC | 763938 | Indel: AGG/AG | |
rpoC | 764005 | Indel: GC/G | |
rpoC | 764365 | Indel: CGG/CG | |
rpoC | 766283 | Indel: ACC/AC | |
rpoC | 766973 | Indel: GCC/GC | |
rpoC | 767149 | Indel: CGG/CG | |
rplC | 801031 | Indel: GT/G | |
embR | 1416971 | Indel: GCC/GC | |
embR | 1417019 | Cys110Tyr | |
rrs | 1472997 | Indel: GCC/GC | |
rrs | 1473362 | Indel: CGG/CG | |
rrl | 1474706 | Indel: GCC/GC | |
rrl | 1474736 | Indel: CGGGGG/CGGGGGG | |
rrl | 1475003 | Indel: GCC/GC | |
rrl | 1475124 | Indel: AGGG/AGG | |
rrl | 1475205 | Indel: GCCC/GCC | |
rrl | 1475682 | Indel: AGG/AG | |
rrl | 1476154 | Indel: GCC/GC | |
rrl | 1476173 | Indel: AGG/AG | |
rrl | 1476692 | Indel: TGG/TCGG | |
Rv1482c-fabG1 | 1673376 | Indel: GCC/GC | |
Rv1482c-fabG1 | 1673425 | C-15T | |
inhA | 1674827 | Indel: AGG/AG | |
inhA | 1674987 | Indel: CGG/CG | |
rpsA | 1834344 | Indel: ACC/AC | |
rpsA | 1834890 | Indel: CGG/CG | |
rpsA | 1834940 | Indel: GA/G | |
tlyA | 1917972 | Leu11Leu | |
tlyA | 1917979 | Indel: CGGGG/CGGG | |
tlyA | 1918267 | Indel: GCC/GC | |
katG | 2154724 | Arg463Leu | |
katG | 2155422 | Indel: C/CG | |
pncA | 2289166 | Indel: CGG/CG | |
kasA | 2518132 | Thr6Thr | |
kasA | 2518598 | Indel: GCC/GC | |
kasA | 2518947 | Indel: TGG/TG | |
kasA | 2519048 | Gly312Ser | |
kasA | 2519270 | Indel: GCC/GC | |
ahpC | 2726419 | Indel: AGG/AG | |
ahpC | 2726436 | Indel: A/AG | |
folC | 2746588 | Indel: GCC/GC | |
folC | 2746630 | Indel: GCC/GC | |
folC | 2746842 | Indel: CGG/CG | |
folC | 2747097 | Indel: CGGG/CGG | |
embC | 4240143 | Indel: TGG/TG | |
embC | 4240585 | Indel: CGG/CG | |
embC | 4240671 | Thr270Ile | |
embC | 4241042 | Asn394Asp | |
embC | 4241263 | Indel: CGG/CG | |
embC | 4242188 | Indel: GCCC/GCC | |
embC | 4242242 | Indel: GT/G | |
embC | 4242622 | Indel: CGG/CG | |
embC | 4242643 | Arg927Arg | |
embC | 4242910 | Indel: CGG/CG | |
embC-embA | 4243185 | Indel: GCCCC/GCCC | |
embA | 4243580 | Val116Val | |
embA | 4243791 | Indel: GCCC/GC | |
embA | 4244187 | Indel: ACC/AC | |
embA | 4244420 | Val396Val | |
embA | 4245170 | Indel: GA/G | |
embA | 4245820 | Indel: GCCC/GCCCC | |
embA | 4245969 | Pro913Ser | |
embA | 4246028 | Indel: GCC/GC | |
embA | 4246503 | Indel: AGGG/AGGGG | |
embB | 4246645 | Indel: GCC/GC | |
embB | 4247169 | Indel: TG/TGG | |
embB | 4247578 | Leu355Leu | |
embB | 4247646 | Glu378Ala | |
embB | 4247670 | Indel: CGG/CG | |
embB | 4248115 | Indel: CGG/CG | lineage2.2.1.1 |
embB | 4248390 | Indel: TGG/TG | |
embB | 4249646 | Indel: CGGG/CGG | |
embB | 4249700 | Indel: TCCC/TCC | |
ethA | 4326510 | Indel: CGG/CG | |
ethA | 4326646 | Indel: GT/G | |
ethA | 4327245 | Indel: CGG/CG | |
gid | 4407588 | Ala205Ala | |
gid | 4407683 | Indel: GC/G | |
gid | 4407873 | Val110Val | |
The estimated accuracy of drug resistance predictions is:
Drug1 | Sensitivity (%) | Specificity (%) |
Isoniazid | 92.8 (89.9-95.7) | 100 (100-100) |
Rifampicin | 96.2 (93.9-98.5) | 98.1 (96.8-99.4) |
Ethambutal | 88.7 (83.6-93.8) | 81.7 (77.6-85.8) |
Pyrazinamide | 70.9 (62.4-79.4) | 93.9 (90.6-97.2) |
Streptomycin | 87.1 (82.7-91.5) | 89.7 (86.0-93.4) |
Ethionamide | 73.6 (66.7-80.5) | 93.3 (89.6-97.0) |
Moxifloxacin | 60.0 (29.6-90.4) | 68.7 (52.6-84.8) |
Ofloxacin | 85.5 (79.1-91.9) | 94.9 (91.8-98.0) |
Amikacin | 82.9 (74.4-91.4) | 98.3 (96.0-100) |
Capreomycin | 60.7 (50.6-70.8) | 90.7 (87.2-94.2) |
Kanamycin | 87.3 (81.3-93.3) | 93.4 (89.9-96.9) |
Para-aminosalisylic acid | Not determined | Not determined |
Linezolid | Not determined | Not determined |
Clofazimine | Not determined | Not determined |
Bedaquiline | Not determined | Not determined |
Multi drug resistance | 91.2 (87.8-94.6) | 98.4 (97.2-99.6) |
Extremely drug resistance | 75.9 (64.5-87.3) | 98.4 (97.3-99.5) |
Lineage2 | Location | Strain | RD type |
lineage1 | Indo-Oceanic | EAI | RD239 |
lineage1.1 | Indo-Oceanic | EAI3;EAI4;EAI5;EAI6 | RD239 |
lineage1.1.1 | Indo-Oceanic | EAI4;EAI5 | RD239 |
lineage1.1.1.1 | Indo-Oceanic | EAI4;ZERO | RD239 |
lineage1.1.2 | Indo-Oceanic | EAI3;EAI5 | RD239 |
lineage1.1.3 | Indo-Oceanic | EAI6 | RD239 |
lineage1.2 | Indo-Oceanic | EAI1;EAI2 | RD239 |
lineage1.2.1 | Indo-Oceanic | EAI2 | RD239 |
lineage1.2.2 | Indo-Oceanic | EAI1 | RD239 |
lineage2 | East-Asian | Beijing | RD105 |
lineage2.1 | East-Asian (non-Beijing) | None | None |
lineage2.2 | East-Asian (Beijing) | Beijing-RD207 | RD105;RD207 |
lineage2.2.2 | East-Asian (Beijing) | Beijing-RD105/RD207 | RD105;RD207 |
lineage2.2.1 | East-Asian (Beijing) | Beijing-RD181 | RD105;RD207;RD181 |
lineage2.2.1.2 | East-Asian (Beijing) | Beijing-RD142 | RD105;RD207;RD181;RD142 |
lineage2.2.1.1 | East-Asian (Beijing) | Beijing-RD150 | RD105;RD207;RD181;RD150 |
lineage3 | East-African-Indian | CAS | RD750 |
lineage3.1 | East-African-Indian | Non-CAS1-Delhi | RD750 |
lineage3.1.1 | East-African-Indian | CAS1-Kili | RD750 |
lineage3.1.2 | East-African-Indian | CAS;CAS2 | RD750 |
lineage3.1.2.1 | East-African-Indian | CAS2 | RD750 |
lineage3.1.2.2 | East-African-Indian | CAS | RD750 |
lineage4 | Euro-American | LAM;T;S;X;H | None |
lineage4.1 | Euro-American | T;X;H | None |
lineage4.1.2 | Euro-American (X-type) | T;H | None |
lineage4.1.2.1 | Euro-American (X-type) | T1;H1 | RD182 |
lineage4.1.1 | Euro-American (X-type) | X1;X2;X3 | None |
lineage4.1.1.2 | Euro-American (X-type) | X1 | None |
lineage4.1.1.1 | Euro-American (X-type) | X2 | RD183 |
lineage4.1.1.3 | Euro-American (Haarlem) | X1;X3 | RD193 |
lineage4.2 | Euro-American | H;T;LAM | None |
lineage4.2.2 | Euro-American (Ural) | T;LAM7-TUR | None |
lineage4.2.2.1 | Euro-American | LAM7-TUR | None |
lineage4.2.1 | Euro-American (TUR) | H3;H4 | None |
lineage4.3 | Euro-American (LAM) | mainly-LAM | None |
lineage4.3.1 | Euro-American (LAM) | LAM9 | None |
lineage4.3.3 | Euro-American (LAM) | LAM;T | RD115 |
lineage4.3.4 | Euro-American (LAM) | LAM | RD174 |
lineage4.3.4.1 | Euro-American (LAM) | LAM1;LAM2 | RD174 |
lineage4.3.4.2 | Euro-American (LAM) | LAM1;LAM4;LAM11 | RD174 |
lineage4.3.4.2.1 | Euro-American (LAM) | LAM11 | RD174 |
lineage4.3.2 | Euro-American (LAM) | LAM3 | None |
lineage4.3.2.1 | Euro-American (LAM) | LAM3 | RD761 |
lineage4.4 | Euro-American | S;T | None |
lineage4.4.2 | Euro-American | T1;T2 | None |
lineage4.4.1 | Euro-American (S-type) | S;T | None |
lineage4.4.1.2 | Euro-American | T1 | None |
lineage4.4.1.1 | Euro-American | S;Orphans | None |
lineage4.5 | Euro-American | H;T | RD122 |
lineage4.6 | Euro-American | T;LAM | None |
lineage4.6.1 | Euro-American (Uganda) | T2 | RD724 |
lineage4.6.1.1 | Euro-American | T2-Uganda | RD724 |
lineage4.6.1.2 | Euro-American | T2 | RD724 |
lineage4.6.2 | Euro-American | T;LAM | RD726 |
lineage4.6.2.1 | Euro-American | T3 | RD726 |
lineage4.6.2.2 | Euro-American (Cameroon) | LAM10-CAM | RD726 |
lineage4.7 | Euro-American (mainly T) | T1;T5 | None |
lineage4.8 | Euro-American (mainly T) | T1;T2;T3;T5 | RD219 |
lineage4.9 | Euro-American (H37Rv-like) | T1 | None |
lineage5 | West-Africa 1 | AFRI_2;AFRI_3 | RD711 |
lineage6 | West-Africa 2 | AFRI_1 | RD702 |
lineage7 | Lineage 7 | None | None |
lineageBOV | M. bovis | BOV_1;BOV_2 | None |
Citations
1. Coll F, et al. Rapid determination of anti-tuberculosis drug resistance from whole genome sequences. Genome Medicine (in press)
2. Coll F, et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nature Communications 2014.