PathogenSeq: TBDR

This tool processes raw sequence data to infer strain type and identify known drug resistance markers.

A stand alone version of this tool is now available and can now be run on linux or mac. Installation instructions can be found on GitHub and on the bioconda page.

This tool is for Research Use Only. Data and information provided through use of this tool are not intended for medical purpose or objective and should not be used for clinical diagnosis, patient management, or human clinical trials.

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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).

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Summary

ID: 5d6f7d8e4f014

Date: Wed Sep 4 10:03:05 2019

Strain: lineage4.2.2;lineage3.1

Drug-resistance: MDR

Drug¹ Resistance Supporting Mutations (frequency)

Isoniazid R katG p.Ile317Val (0.36), katG p.Ser315Thr (1.00)

Rifampicin R rpoB p.Asp435Val (0.80), rpoB p.Ser450Leu (0.29)

Ethambutol R embB p.Met306Val (0.18), embB p.Gln497Arg (0.75)

Pyrazinamide R pncA c.194 195insA (0.33)

Streptomycin

Ethionamide

Fluoroquinolones

Amikacin

Capreomycin

Kanamycin

Lineage² Family Main Spoligotype RDS

lineage4 Euro-American LAM;T;S;X;H None

lineage3.1 East-African-Indian Non-CAS1-Delhi RD750

lineage4.2 Euro-American H;T;LAM None

lineage4.2.2 Euro-American (Ural) T;LAM7-TUR None

Mutations in candidate genes:

Gene	Chromosome Position	Mutation	Estimated fraction
gyrB	7033	c.1794G>A	0.182
gyrA	7362	p.Glu21Gln	1.000
gyrA	7585	p.Ser95Thr	1.000
gyrA	8414	c.1113C>T	0.143
gyrA	8688	p.Ala463Ser	0.706
gyrA	8869	p.Thr523Met	0.400
gyrA	9304	p.Gly668Asp	1.000
rpoB	761489	c.1683G>A	0.625
rpoC	763537	c.168C>G	0.133
rpoC	763546	c.177A>G	0.138
rpoC	763570	c.201G>C	0.138
rpoC	763573	c.204G>C	0.138
rpoC	763594	c.225C>T	0.154
rpoC	763622	p.Ala85Ser	0.148
rpoC	764018	p.Asp217His	0.188
rpoC	765588	p.Pro740Gln	0.200
rpoC	766490	p.Arg1041Cys	0.160
rpoC	766957	p.Glu1196Asp	0.200
rpsL	781395	c.-165T>C	1.000
rpsL	781436	c.-124C>G	0.222
embR	1416222	p.Phe376Leu	0.185
embR	1416234	p.Cys372Gly	0.207
rrs	1472085	r.240c>t	0.364
rrs	1473053	r.1208t>a	0.200
rrl	1474156	r.499g>t	0.400
rrl	1474823	r.1166c>g	0.308
rrl	1474827	r.1170c>t	0.308
rrl	1474830	r.1173a>g	0.308
rrl	1474831	r.1174a>t	0.308
rrl	1474853	r.1196a>g	0.286
rrl	1474864	r.1207c>t	0.286
rrl	1475704	r.2047c>t	0.200
rrl	1475803	r.2146t>c	0.231
rrl	1475804	r.2147g>c	0.231
rrl	1475816	r.2159c>g	0.143
rrl	1475817	r.2160a>g	0.143
rrl	1476356	r.2699c>a	0.200
rrl	1476357	r.2700t>c	0.200
rrl	1476425	r.2768g>a	0.250
rrl	1476463	r.2806c>t	0.214
rrl	1476466	r.2809c>t	0.214
rrl	1476481	r.2824t>c	0.167
rrl	1476506	r.2849t>c	0.158
tlyA	1917972	c.33A>G	1.000
katG	2154724	p.Arg463Leu	0.174
katG	2155166	p.Gly316Cys	0.250
katG	2155182	p.Lys310Asn	0.182
katG	2155488	p.Glu208Asp	0.160
katG	2155742	p.Gly124Cys	0.200
ahpC	2726105	c.-88G>A	0.200
ahpC	2726251	p.Gly20Val	0.133
ald	3086788	c.-32T>C	1.000
alr	3840619	p.Asp268Tyr	0.211
embC	4240172	p.Val104Met	0.250
embC	4241077	c.1215C>A	0.200
embC	4242075	p.Arg738Gln	0.407
embC	4242643	c.2781C>T	1.000
embB	4247610	p.Ser366Leu	0.138
ethA	4327085	p.Thr130Ile	0.200
gid	4408100	c.102 102del	0.882

Analysis pipeline specifications

TBProfiler Version: 2.1.1

Analysis	Program
Mapping	bwa
Variant Calling	BCFtools

Log

Drug Details

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)

Lineages

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.

Disclaimer

This tool is for Research Use Only and is offered free for use. The London School of Hygiene and Tropical Medicine shall have no liability for any loss or damages of any kind, however sustained relating to the use of this tool.

Drug¹	Resistance	Supporting Mutations (frequency)
Isoniazid	R	katG p.Ile317Val (0.36), katG p.Ser315Thr (1.00)
Rifampicin	R	rpoB p.Asp435Val (0.80), rpoB p.Ser450Leu (0.29)
Ethambutol	R	embB p.Met306Val (0.18), embB p.Gln497Arg (0.75)
Pyrazinamide	R	pncA c.194 195insA (0.33)
Streptomycin
Ethionamide
Fluoroquinolones
Amikacin
Capreomycin
Kanamycin

Lineage²	Family	Main Spoligotype	RDS
lineage4	Euro-American	LAM;T;S;X;H	None
lineage3.1	East-African-Indian	Non-CAS1-Delhi	RD750
lineage4.2	Euro-American	H;T;LAM	None
lineage4.2.2	Euro-American (Ural)	T;LAM7-TUR	None