DOI: 10.5061/dryad.qjq2bvqs6
title: Data from: Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: A multicentre clinical study of two end-to-end commercial workflows

description: Background: Drug-resistant tuberculosis remains a major obstacle in ending
 the global tuberculosis epidemic. Deployment of molecular tools for
 comprehensive drug resistance profiling is imperative for successful
 detection and characterisation of tuberculosis drug resistance. We aimed
 to assess the diagnostic accuracy of a new class of molecular diagnostics
 for drug-resistant tuberculosis. Methods: We conducted a prospective,
 cross-sectional, multicentre clinical evaluation of the performance of two
 targeted next-generation sequencing (tNGS) assays for drug-resistant
 tuberculosis at reference laboratories in three countries (Georgia, India,
 and South Africa) to assess diagnostic accuracy and index test failure
 rates. Eligible participants were aged 18 years or older, with molecularly
 confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant
 tuberculosis. Sensitivity and specificity for both tNGS index tests
 (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT]
 Tuberculosis Drug Resistance Test) were calculated for rifampicin,
 isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second
 line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide,
 bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against
 a composite reference standard of phenotypic drug susceptibility testing
 and whole-genome sequencing. Findings: Between April 1, 2021, and June 30,
 2022, 832 individuals were invited to participate in the study, of whom
 720 were included in the final analysis (212, 376, and 132 participants in
 Georgia, India, and South Africa, respectively). Of 720 clinical sediment
 samples evaluated, 658 (91%) and 684 (95%) produced complete or partial
 results on the GenoScreen and ONT tNGS workflows, respectively, with 593
 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence
 data. Both workflows had sensitivities and specificities of more than 95%
 for rifampicin and isoniazid, and high accuracy for fluoroquinolones
 (sensitivity approximately ≥94%) and second line-injectables (sensitivity
 80%) compared with the composite reference standard. Importantly, these
 assays also detected mutations associated with resistance to critical new
 and repurposed drugs (bedaquiline, linezolid) not currently detectable by
 any other WHO-recommended rapid diagnostics on the market. We note that
 the current format of assays have low sensitivity (≤50%) for linezolid and
 more work on mutations associated with drug resistance is needed.
 Interpretation: This multicentre evaluation demonstrates that culture-free
 tNGS can provide accurate sequencing results for detection and
 characterisation of drug resistance from Mycobacterium tuberculosis
 clinical sediment samples for timely, comprehensive profiling of
 drug-resistant tuberculosis.
description: Participants meeting eligibility criteria were asked to provide
 at least 6 mL sputum either in one or two samples collected on day 1 and
 day 2. Samples were homogenized, decontaminated, re-suspended in 4mL final
 volume for all downstream testing. MTB/RIF, acid-fast bacilli (AFB) smear,
 Hain MTBDRplus and MTBDRsl, Mycobacteria Growth Indicator Tube (MGIT) and
 Löwenstein–Jensen medium (LJ) culture were performed on the sediment for
 standard of care testing. MGIT pDST was performed for all culture-positive
 samples for RIF, INH, FQ (MFX, LFX), PZA, AMK, CAP, KAN, BDQ, LZD, CLF,
 STR, and EMB at WHO endorsed critical concentrations. 
description: # Data from: Evaluating culture-free targeted next-generation sequencing
 for diagnosing drug-resistant tuberculosis: A multicentre clinical study
 of two end-to-end commercial workflows
 [https://doi.org/10.5061/dryad.dr7sqvb8m](https://doi.org/10.5061/dryad.dr7sqvb8m) ## Description of the data and file structure Associated per sample clinical, genetic reference, phenotypic drug susceptibility, and tNGS results for Mycobacterium tuberculosis collected during the Seq&Treat clinical trial sponsored by FIND, the Foundation for Innovative New Diagnostics ### Files and variables #### File: dryad.txt **Description:**  ##### Variables * insdc_biosample_accession: Unique BioSample Accession ID linking to publicly available sequencing data at the INSDC * antibiotic: drug name * dst_method: Culture Medium used to perform the phenotypic susceptibility testing * critical_concentration: Concentration at which the antibiotic was tested * resistance_phenotype: Susceptible or resistant result #### File: S_T_performance_metadata_dryad.txt **Description:**  ##### Variables * StudyID: Study ID; text * BioSample ID: Unique BioSample Accession ID linking to publicly available sequencing data at the NCBI; text * studyCAT: study category; early exclusion, missing one or more index test, no pheno reference, no WGS reference, analysis set * GENDER: Sex; converted to numeric binary values for participant privacy, Unknown * RISK_YN: Any risk factors for drug resistant TB ?; Yes, No * RIF_RESIST_YN: a. A positive RIF-resistance result by Xpert MTB/RIF OR Xpert MTB/RIF Ultra (i.e., “RIF resistance DETECTED”); Yes, No * NOT_RESP_TX_YN: b. Not responding TB treatment with positive sputum smear or culture after ≥ 3 months of standard TB treatment; Yes, No * PREV_DIAG_YN: c. Previously diagnosed with Rif-resistant/MDR-TB and failed TB treatment with positive sputum smear or culture after ≥ 3months of a standard MDR-TB regimen; Yes, No * PREV_TX_YN: d. Previously received &gt;1 month of treatment for a prior TB episode; Yes, No * CONTACT_YN: e. Close contact with a known drug-resistant TB case; Yes, No * ICF_YN: Informed consent signed by participant; Yes, No * SPUTUM_YN: Willingness to provide sputum samples at enrolment; Yes, No * TX_STARTED_YN: Has started treatment for current TB episode more than 7 days prior to enrolment date (i.e, date of filling this form); No, Yes * SP1_COL_YN: Is sputum collected?; Yes, No * SP1_VOL_YN: Is sputum volume approximately ≥ 3 mL?; Yes, No * SP1_VISC: Sputum Viscocity; Very viscous, Viscous, Not viscous / Watery * SP1_PUR: Sputum Purity; Containing food or other particules, Not containing particles * SP1_BLOOD: Presence of Blood; Very blood stained, Midly blood stained, Not blood stained * SP2_VOL_YN: Is sputum volume approximately ≥ 3 mL?; Yes, No * SP2_VISC: Sputum Viscocity; Very viscous, Viscous, Not viscous / Watery * SP2_PUR: Sputum Purity; Containing food or other particules, Not containing particles * SP2_BLOOD: Presence of Blood; Very blood stained, Midly blood stained, Not blood stained * COUGH: Cough; Yes, No * COUGH_DUR: Cough duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * FEVER: Fever; Yes, No * FEVER_DUR: Fever duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * SWEAT: Night sweats; Yes, No * SWEAT_DUR: Night sweats duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * WEIGHT_LOSS: Weight loss (without diet); Yes, No * WEIGHT_LOSS_DUR: Weight loss duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * HEMOPT: Hemoptysis (coughing blood); Yes, No * HEMOPT_DUR: Hemoptysis duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * SYMPT_OTH: Other symptoms?; Yes, No * SYMPT_OTH_DUR: Other symptoms duration; &lt;2 weeks, 2-8 weeks, &gt;8 weeks * SYMPT_OTH_SPE: Please specify other symptoms; text * PREV_TB_YN: Previous history of tuberculosis (TB)?; Yes, No, Don't know * TB_LOC: Location of TB infection; Pulmonary, Extrapulmonary, Don't know, Other * TB_NAT: Nature of TB infection; Drug-susceptible TB, Drug-resistant TB, Don’t know * TX_UNK: List of TB treatment drugs previously used (most recent treatment); Don't know * DRUG_1: DRUG_1; text * DRUG_2: DRUG_2; text * DRUG_3: DRUG_3; text * DRUG_4: DRUG_4; text * DRUG_5: DRUG_5; text * DRUG_6: DRUG_6; text * DRUG_7: DRUG_7; text * DRUG_8: DRUG_8; text * TB_TX_COMP_YN: Has the most recent TB treatment been completed?; Yes, No, Don't know * TB_CURED_YN: If treatment was completed, was the patient considered to be cured?; Yes, No, Don't know * WEIGHT: Weight (kg) rounded to 5 for participant privacy; Numeric * WEIGHT_ND: Weight not done; Not done * TEMP: Temperature (°C); Numeric * TEMP_ND: Temperature not done; Not done * APPEAR: General appearance; Not ill (healthy and strong impression throughout examination), Mildly ill (able to carry out routine activities, but symptomatic with fatigue, cough, etc. upon careful inspection), Moderately ill (some impairment of activities; visibly ill to a lay person; still ambulatory and mostly self-sufficient but clearly symptomatic), Gravely ill (unable to carry out usual activities. Visibly distressed. Requires hospitalization) * SP1_COMM_CRF3: Comments; text * XRAY_YN: Chest X-Ray done; Yes, No * XRAY_FIND: Chest X-Ray finding; Normal, Abnormal – Not TB (e.g. scoliosis), Abnormal – May be compatible with TB, Not done * XRAY_LOC_ABNORM: Localization of abnormality; Left upper zone, Left mid zone, Left lower zone, Diffused, Right upper zone, Right mid zone, Right lower zone * XRAY_FEAT: Chest X-ray image features; Infiltrate, Miliary, Cavity, Pleural, Lymphadenopathy, Micronodules, Consolidation, Tuberculoma * XRAY_CONCL: Chest X-Ray conclusion; TB Likely (pulmonary pleural or pericardial), Pneumonia or Atypical TB, Pneumonia (TB unlikely), Other * XRAY_CONCL_SPE: Specify other conclusion; Pneumonic consolidation, Pneumonitis ? Koch"s * XRAY_ND: Please explain; text * SP_REC_YN: Have two sputum samples been received?; Yes, No * SP_REC_REASON_ND: Please explain; text * SP_POOL_VOL: What is the pooled sputum volume (mL); numeric * XPERT_YN: Test performed?; Yes, No * XPERT_RES_CRF5: Xpert result; MTB POS, MTB NEG, Invalid/Error/No result * XPERT_CYCLE_THRESH: Cycle threshold range; Very low, Low, Medium, High * XPERT_CT_1: CT_1 value; numeric * XPERT_CT_2: CT_2 value; numeric * XPERT_CT_3: CT_3 value; numeric * XPERT_CT_4: CT_4 value; numeric * XPERT_CT_5: CT_5 value; numeric * XPERT_RIF_RESIST: RIF resistance; Detected, Not detected, Indeterminate * XPERT_REP_YN: Xpert test repeated?; Yes, No * XPERT_RES_REP: Xpert result; MTB POS, MTB NEG, Invalid/Error/No result * XPERT_CYCLE_THRESH_REP: Cycle threshold range; Very low, Low, Medium, High * XPERT_RIF_RESIST_REP: RIF resistance; Detected, Not detected, Indeterminate * XPERT_RES_Combined: Xpert Mtb Detection Combined; MTB POS, MTB NEG, Invalid/Error/No result * XPERT_RIF_RESIST_Combined: RIF resistance Combined; Detected, Not detected, Indeterminate * XPERT_CT_REP_1: CT_REP_1 value; numeric * XPERT_CT_REP_2: CT_REP_2 value; numeric * XPERT_CT_REP_3: CT_REP_3 value; numeric * XPERT_CT_REP_4: CT_REP_4 value; numeric * XPERT_CT_REP_5: CT_REP_5 value; numeric * XPERT_REAS_ND: Please explain; text * XPERT_CYCLE_THREST_COMBINED: Cycle threshold combined; High, medium, low, very low * MICRO_YN: Test performed?; Yes, No * MICRO_RES: Smear result; Positive, Negative * MICRO_GRADE: Smear positivity grade; Scanty, 1+, 2+, 3+ * ALIQ_YN: Aliquot preparation done?; Yes, No * ALIQ_NUM: Number of Aliquots frozen; 1, 2, 3, 4, 5, Other * TEST_COMM_CRF5: Comments; text * MGIT_RES: MGIT 960 result; Positive, Negative * MGIT_RES_T: MGIT 960 Time to Detection (Days/Hours); day/hour * LJ_RES: LJ slant result; Presumptive MTB positive, MTB positive, Negative, Contaminated * SPEC_YN: Speciation test performed?; Yes, No * SPEC_RES: Speciation result; MTB Complex, NTM * SPEC_REAS_ND: Please explain; text * DNA_EXTR_YN: DNA extraction performed; Yes, No * DNA_QUANT: DNA Quantification (ng/µL); number * DNA_EXTR_REAS_ND: Please explain; text * DST_YN: MGIT DST performed?; Yes, No * pDST_RES_calc: Is there a valid pDST result available; Yes, No * DST_SRC: MGIT DST culture source; Original, Decontaminated/subculture * DST_REAS_ND: Please explain; text * RIFL: Rifampicin (Low); [R] Resistant, [S] Susceptible, [X] Error * RIFL_CC: RIF(Low) Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * RIFH: Rifampicin (High); [R] Resistant, [S] Susceptible, [X] Error * RIFH_CC: RIF(High) Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * INH: Isoniazid; [R] Resistant, [S] Susceptible, [X] Error * INH_CC: INH Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * SM: Streptomycin; [R] Resistant, [S] Susceptible, [X] Error * SM_CC: SM Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * EMB: Ethambutol; [R] Resistant, [S] Susceptible, [X] Error * EMB_CC: EMB Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * PZA: Pyrazinamide; [R] Resistant, [S] Susceptible, [X] Error * PZA_CC: PZA Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * MFXL: Moxifloxacin (Low); [R] Resistant, [S] Susceptible, [X] Error * MFXL_CC: MFX(Low) Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * MFXH: Moxifloxacin (High); [R] Resistant, [S] Susceptible, [X] Error * MFXH_CC: MFX(High) Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * LFX: Levofloxacin; [R] Resistant, [S] Susceptible, [X] Error * LFX_CC: LFX Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * AMK: Amikacin; [R] Resistant, [S] Susceptible, [X] Error * AMK_CC: AMK Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * KAN: Kanamycin; [R] Resistant, [S] Susceptible, [X] Error * KAN_CC: KAN Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * CAP: Capreomycin; [R] Resistant, [S] Susceptible, [X] Error * CAP_CC: CAP Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * BDQ: Bedaquiline; [R] Resistant, [S] Susceptible, [X] Error * BDQ_CC: BDQ Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * LZD: Linezolid; [R] Resistant, [S] Susceptible, [X] Error * LZD_CC: LZD Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * CLF: Clofazimine; [R] Resistant, [S] Susceptible, [X] Error * CLF_CC: CLF Critical concentration µg/ml; 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 100 * OTH_1: ${OTH_R_ID}. Other; Ethionamide * OTH_RES_1: ${OTH_R_ID}. Result (other); [R] Resistant, [S] Susceptible, [X] Error * OTH_CC__1: ${OTH_R_ID}. Critical concentration µg/ml; number * FQ: Combined MFXL and LFX, resistance in either = R (OR); [R] Resistant=if either pDST MFXL or LFX is "R", [S] Susceptible=if both pDST MFXL and LFX are "S" * WGS_YN_calc: Was WGS result available; Yes, No * WGS_RIF: Rifampicin resistance detection; R=Resistant, S=Susceptible * WGS_RIF_Mut: Rifampicin resistance associated mutation; list of resistance associated mutations * WGS_INH: Isoniazid resistance detection; R=Resistant, S=Susceptible * WGS_INH_Mut: Isoniazid resistance associated mutation; list of resistance associated mutations * WGS_MFX: Moxifloxacin resistance detection; R=Resistant, S=Susceptible * WGS_MFX_Mut: Moxifloxacin resistance associated mutation; list of resistance associated mutations * WGS_LFX: Levofloxacin resistance detection; R=Resistant, S=Susceptible * WGS_LFX_Mut: Levofloxacin resistance associated mutation; list of resistance associated mutations * WGS_AMK: Amikacin resistance detection; R=Resistant, S=Susceptible * WGS_AMK_Mut: Amikacin resistance associated mutation; list of resistance associated mutations * WGS_CAP: Capreomycin resistance detection; R=Resistant, S=Susceptible * WGS_CAP_Mut: Capreomycin resistance associated mutation; list of resistance associated mutations * WGS_KAN: Kanamycin resistance detection; R=Resistant, S=Susceptible * WGS_KAN_Mut: Kanamycin resistance associated mutation; list of resistance associated mutations * WGS_PZA: Pyrazinamide resistance detection; R=Resistant, S=Susceptible * WGS_PZA_Mut: Pyrazinamide resistance associated mutation; list of resistance associated mutations * WGS_LZD: Linezolid resistance detection; R=Resistant, S=Susceptible * WGS_LZD_Mut: Linezolid resistance associated mutation; list of resistance associated mutations * WGS_EMB: Ethambutol resistance detection; R=Resistant, S=Susceptible * WGS_EMB_Mut: Ethambutol resistance associated mutation reported; list of resistance associated mutations * WGS_ETH: Ethionamide resistance detection; R=Resistant, S=Susceptible * WGS_ETH_Mut: Ethionamide resistance associated mutation reported; list of resistance associated mutations * WGS_SM: Streptomycin resistance detection; R=Resistant, S=Susceptible * WGS_SM_Mut: Streptomycin resistance associated mutation reported; list of resistance associated mutations * GS_YN_calc: Was GS result available; Yes, No * GS_Sequencingresultacceptabili; Sequencing result acceptability; ND=Mycobacteria not detected, -=One or more resistance-associated position in the database not covered, +=All resistance-associated positions in database with enough data to identify mutations from 80-100%, ++=All resistance-associated positions in database with enough data to identify mutations from 10-100%, +++=All resistance-associated positions in database with enough data to identify mutations from 3-100% * GS_RIF: Rifampicin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_RIF_Mut: Rifampicin resistance associated mutation reported; list of resistance associated mutations * GS_INH: Isoniazid resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_INH_Mut: Isoniazid resistance associated mutation reported; list of resistance associated mutations * GS_FQ: Fluoroquinolone resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_FQ_Mut: Fluoroquinolone resistance associated mutation reported; list of resistance associated mutations * GS_AMK: Amikacin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_AMK_Mut: Amikacin resistance associated mutation reported; list of resistance associated mutations * GS_CAP: Capreomycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_CAP_Mut: Capreomycin resistance associated mutation reported; list of resistance associated mutations * GS_KAN: Kanamycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_KAN_Mut: Kanamycin resistance associated mutation reported; list of resistance associated mutations * GS_PZA: Pyrazinamide resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_PZA_Mut: Pyrazinamide resistance associated mutation reported; list of resistance associated mutations * GS_BDQ: Bedaquiline resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_BDQ_Mut: Bedaquiline resistance associated mutation reported; list of resistance associated mutations * GS_LZD: Linezolid resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_LZD_Mut: Linezolid resistance associated mutation reported; list of resistance associated mutations * GS_CLF: Clofazimine resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_CLF_Mut: Clofazimine resistance associated mutation reported; list of resistance associated mutations * GS_EMB: Ethambutol resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_EMB_Mut: Ethambutol resistance associated mutation reported; list of resistance associated mutations * GS_ETH: Ethionamide resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_ETH_Mut: Ethionamide resistance associated mutation reported; list of resistance associated mutations * GS_SM: Streptomycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (sequenced but no call) * GS_SM_Mut: Streptomycin resistance associated mutation reported; list of resistance associated mutations * ONT_YN_calc: Was ONT result available; Yes, No * ONT_RIF: Rifampicin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_RIF_Mut: Rifampicin resistance associated mutation reported; list of resistance associated mutations * ONT_INH: Isoniazid resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_INH_Mut: Isoniazid resistance associated mutation reported; list of resistance associated mutations * ONT_PZA: Pyrazinamide resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_PZA_Mut: Pyrazinamide resistance associated mutation reported; list of resistance associated mutations * ONT_EMB: Ethambutol resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_EMB_Mut: Ethambutol resistance associated mutation reported; list of resistance associated mutations * ONT_SM: Streptomycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_SM_Mut: Streptomycin resistance associated mutation reported; list of resistance associated mutations * ONT_LFX: Levofloxacin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_LFX_Mut: Levofloxacin resistance associated mutation reported; list of resistance associated mutations * ONT_MFX: Moxifloxacin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_MFX_Mut: Moxifloxacin resistance associated mutation reported; list of resistance associated mutations * ONT_KAN: Kanamycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_KAN_Mut: Kanamycin resistance associated mutation reported; list of resistance associated mutations * ONT_AMK: Amikacin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_AMK_Mut: Amikacin resistance associated mutation reported; list of resistance associated mutations * ONT_CAP: Capreomycin resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_CAP_Mut: Capreomycin resistance associated mutation reported; list of resistance associated mutations * ONT_ETH: Ethionamide resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_ETH_Mut: Ethionamide resistance associated mutation reported; list of resistance associated mutations * ONT_LZD: Linezolid resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_LZD_Mut: Linezolid resistance associated mutation reported; list of resistance associated mutations * ONT_BDQ: Bedaquiline resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_BDQ_Mut: Bedaquiline resistance associated mutation reported; list of resistance associated mutations * ONT_CLF: Clofazimine resistance detection; R=Resistant, S=Susceptible, U=Undetermined (target failure) * ONT_CLF_Mut: Clofazimine resistance associated mutation reported; list of resistance associated mutations * ONT_status: ONT classification; fail, no result found in output files, pass, positive * gsRIF: re-classed GS result for RIF; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsINH: re-classed GS result for INH; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsSM: re-classed GS result for SM; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsEMB: re-classed GS result for EMB; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsPZA: re-classed GS result for PZA; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsFQ: re-classed GS result for FQ; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsAMK: re-classed GS result for AMK; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsKAN: re-classed GS result for KAN; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsCAP: re-classed GS result for CAP; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsBDQ: re-classed GS result for BDQ; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsLZD: re-classed GS result for LZD; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * gsCLF: re-classed GS result for CLF; susceptible, resistant, uncharacterized, target failure, sequence failure, not performed * ontRIF: re-classed ONT result for RIF; susceptible, resistant, target failure, sequence failure, not performed * ontINH: re-classed ONT result for INH; susceptible, resistant, target failure, sequence failure, not performed * ontSM: re-classed ONT result for SM; susceptible, resistant, target failure, sequence failure, not performed * ontEMB: re-classed ONT result for EMB; susceptible, resistant, target failure, sequence failure, not performed * ontPZA: re-classed ONT result for PZA; susceptible, resistant, target failure, sequence failure, not performed * ontMFX: re-classed ONT result for MFX; susceptible, resistant, target failure, sequence failure, not performed * ontLFX: re-classed ONT result for LFX; susceptible, resistant, target failure, sequence failure, not performed * ontAMK: re-classed ONT result for AMK; susceptible, resistant, target failure, sequence failure, not performed * ontKAN: re-classed ONT result for KAN; susceptible, resistant, target failure, sequence failure, not performed * ontCAP: re-classed ONT result for CAP; susceptible, resistant, target failure, sequence failure, not performed * ontBDQ: re-classed ONT result for BDQ; susceptible, resistant, target failure, sequence failure, not performed * ontLZD: re-classed ONT result for LZD; susceptible, resistant, target failure, sequence failure, not performed * ontCLF: re-classed ONT result for CLF; susceptible, resistant, target failure, sequence failure, not performed * cRIFL: pDST and WGS composite RIF; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cINH: pDST and WGS composite INH; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cSM: pDST and WGS composite SM; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cPZA: pDST and WGS composite PZA; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cMFXL: pDST and WGS composite MFXL; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cLFX: pDST and WGS composite LFX; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cFQ: pDST and WGS compositeFQ; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cAMK: pDST and WGS composite AMK; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cCAP: pDST and WGS composite CAP; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cKAN: pDST and WGS composite KAN; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cLZD: pDST and WGS composite LZD; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cEMB: pDST and WGS composite EMB; [R] Resistant=if either WGS and pDST are "R", [S] Susceptible=if both WGS and pDST are "S", WGS only, pDST only, noPDST or WGS * cGS_RIF: GS sequencing result for RIF; success, target failure, sequence failure * cGS_INH: GS sequencing result for INH; success, target failure, sequence failure * cGS_FQ: GS sequencing result for FQ; success, target failure, sequence failure * cGS_AMK: GS sequencing result for AMK; success, target failure, sequence failure * cGS_CAP: GS sequencing result for CAP; success, target failure, sequence failure * cGS_KAN: GS sequencing result for KAN; success, target failure, sequence failure * cGS_PZA: GS sequencing result for PZA; success, target failure, sequence failure * cGS_BDQ: GS sequencing result for BDQ; success, target failure, sequence failure * cGS_LZD: GS sequencing result for LZD; success, target failure, sequence failure * cGS_CLF: GS sequencing result for CLF; success, target failure, sequence failure * cGS_EMB: GS sequencing result for EMB; success, target failure, sequence failure * cGS_SM: GS sequencing result for SM; success, target failure, sequence failure, not run * cGS_sequence: GS sequencing overall result; sequence failure, partial sequence, complete sequence, not run * cONT_RIF: ONT sequencing result for RIF; success, target failure, sequence failure * cONT_INH: ONT sequencing result for INH; success, target failure, sequence failure * cONT_PZA: ONT sequencing result for PZA; success, target failure, sequence failure * cONT_EMB: ONT sequencing result for EMB; success, target failure, sequence failure * cONT_SM: ONT sequencing result for SM; success, target failure, sequence failure * cONT_LFX: ONT sequencing result for LFX; success, target failure, sequence failure * cONT_MFX: ONT sequencing result for MFX; success, target failure, sequence failure * cONT_KAN: ONT sequencing result for KAN; success, target failure, sequence failure * cONT_AMK: ONT sequencing result for AMK; success, target failure, sequence failure * cONT_CAP: ONT sequencing result for CAP; success, target failure, sequence failure * cONT_BDQ: ONT sequencing result for BDQ; success, target failure, sequence failure * cONT_LZD: ONT sequencing result for LZD; success, target failure, sequence failure * cONT_CLF: ONT sequencing result for CLF; success, target failure, sequence failure * cONT_sequence: ONT sequencing overall result; sequence failure, partial sequence, complete sequence, not run ## Access information Other publicly accessible locations of the data: * [https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1160005](https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1160005) ## Version changes **11-August-2025:** Added additional data file to include tNGS results, WGS calls, pDST, and clinical metadata. "WEIGHT" data column was rounded to the nearest 5 to protect participant privacy, and "GENDER" data column was converted to numeric binary values to protect participant privacy. The readme file was updated. ## Human subjects data This dataset has been de-identified and is publicly available in accordance with participant consent and ethical research standards. All participants provided informed consent for their de-identified data to be shared in a public data repository for the purposes of scientific research and transparency. De-identification was carried out by removing all direct identifiers and indirect identifiers. Additionally, all free-text fields were reviewed to ensure that no potentially identifying information was retained. The dataset was reviewed to confirm that no combination of variables could reasonably lead to re-identification of individual participants.