Comparative assessment of line-probe assays and targeted next-generation sequencing in drug-resistant tuberculosis diagnosis

Data files

Aug 19, 2025 version files 704.68 KB

README.md

6.43 KB
Seq_Treat_LPA_data.txt

698.25 KB

Abstract

Background

Rapid and accurate detection of drug-resistant tuberculosis (DR-TB) is crucial for ensuring effective treatment, halting transmission and preventing the amplification of resistance. Comparative evaluations of molecular diagnostic assays in high-burden settings are essential for informing clinical decision-making for DR-TB treatment.

Findings

Among 720 clinical samples tested, MTBDRplus LPA sensitivity for rifampicin and isoniazid was 92.3 % (95 % CI 88.9–94.8) and 91.9 % (88.4–94.4), each significantly lower than ≥95% achieved by both tNGS workflows (p < 0.01). For fluoroquinolones (moxifloxacin and levofloxacin), the MTBDRsl LPA and ONT had similar sensitivities (94.3% and 92.7%, and 94.8% and 93.9%, respectively), while GenoScreen outperformed both (97.3% and 96.6%). GenoScreen also demonstrated the highest sensitivity for amikacin resistance (94.6%) compared to LPAs (88.7%) and ONT (88.3%). Complete assay failure rates were low for LPAs (4.9%) and ONT (5.0%) and moderately higher for GenoScreen (8.6%), with differences in single-target failures across all assays.

Interpretation

LPAs demonstrated lower sensitivity and more limited drug resistance detection compared to tNGS workflows, underscoring the advantages of tNGS for improving DR-TB diagnostic algorithms. These findings provide critical evidence to guide updates in DR-TB diagnostic programs.

Description of the data and file structure

Per patient LPA results with variables for participant ID and NCBI Biosample ID for association with manuscript "Evaluating culture-free targeted next-generation
sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows"

Files and variables

File: Seq&Treat_LPA_data.txt

Description:

Variables

ParticipantID: Unique Participant ID; text
BioSample ID: Unique BioSample Accession ID linking to publicly available sequencing data at the NCBI; text
PLUS_AMP_CTL: PLUS AMP CTL Presence of Hain MTBDRplus amplification control POSITIVE NEGATIVE;
PLUS_AMP_CTL_REP: PLUS AMP CTL REP Presence of Hain MTBDRplus amplification control on repeated test if done POSITIVE NEGATIVE NA;
PLUS_CON_CTL: PLUS CON CTL Presence of Hain MTBDRplus Conjugate control POSITIVE NEGATIVE;
PLUS_CON_CTL_REP: PLUS CON CTL REP Presence of Hain MTBDRplus Conjugate control on repeated test if done POSITIVE NEGATIVE NA;
PLUS_RES: PLUS RES Presence of Hain MTBDRplus Mtb complex specific control TUB POSITIVE NEGATIVE Invalid Indeterminate;
RPOB_RES: RPOB RES Hain MTBDRplus rpoB band results;
*LPA_RIF: LPA RIF Hain MTBDRplus RIF result S susceptible R resistant NA not available Inv Invalid;
WHO_CALL_RIF: WHO CALL RIF Interpretation of MTBDRplus RIF call as per WHO guidelines R detected Resistance detected R inferred Resistance inferred R not detected Resistance not detected Invalid Indeterminate;
KATG_RES: KATG RES Hain MTBDRplus katG band results;
INHA_RES: INHA RES Hain MTBDRplus inhA band results;
LPA_INH: LPA INH Hain MTBDRplus INH result S susceptible R resistant NA not available Inv Invalid;
WHO_CALL_INH: WHO CALL INH Interpretation of MTBDRplus INH call as per WHO guidelines R detected Resistance detected R inferred Resistance inferred R not detected Resistance not detected Invalid Indeterminate;
SL_YN: SL YN Hain MTBDRsl run not done, done;
SL_AMP_CTL: SL AMP CTL Presence of Hain MTBDRsl amplification control POSITIVE NEGATIVE;
SL_AMP_CTL_REP: SL AMP CTL REP Presence of Hain MTBDRsl amplification control on repeated test if done POSITIVE NEGATIVE NA;
SL_CON_CTL: SL CON CTL Presence of Hain MTBDRsl Conjugate control POSITIVE NEGATIVE;
SL_CON_CTL_REP: SL CON CTL REP Presence of Hain MTBDRsl Conjugate control on repeated test if done POSITIVE NEGATIVE NA;
SL_RES: SL RES Presence of Hain MTBDRsl Mtb complex specific control TUB POSITIVE NEGATIVE Invalid Indeterminate;
GYRA_RES: GYRA RES Hain MTBDRsl gyrA band results;
GYRB_RES: GYRB RES Hain MTBDRsl gyrB band results;
LPA_FQ: LPA FQ Hain MTBDRsl FQ result S susceptible R resistant NA not available Inv Invalid;
WHO_CALL_FQ: WHO CALL FQ Interpretation of of MTBDRsl FQ call as per WHO guidelines R detected Resistance detected R inferred Resistance inferred R not detected Resistance not detected Invalid Indeterminate;
RRS_RES: RRS RES Hain MTBDRsl rrs band results;
EIS_RES: EIS RES Hain MTBDRsl eis band results;
LPA_AMK: LPA AMK Hain MTBDRsl AMK result S susceptible R resistant NA not available Inv Invalid;
WHO_CALL_AMK: WHO CALL AMK Interpretation of of MTBDRsl AMK call as per WHO guidelines R detected Resistance detected R inferred Resistance inferred R not detected Resistance not detected Invalid Indeterminate;
LPA_COMM: LPA COMM Laboratory notes;
LPA_sample_failure: LPA sample failure; indicates whether a sample failed both the MTBDRplus and MTBDRsl assays; "Passed" indicates a successful result, while "Failed" indicates a sample failure, which occurs if the TUB band is absent and/or the control bands for all four drug target gene loci are missing.
LPA_RIF_failure: LPA RIF failure; sample that failed to provide a result for RIF. "Passed" indicates a successful result for RIF, while "Target failure" indicates a failed results for RIF due to the absence TUB and the lack of the control bands for the RPOB gene locus.
LPA_INH_failure: LPA INH failure; sample that failed to provide a result for INH. "Passed" indicates a successful result for INH , while "Target failure" indicates a failed results for INH due to the absence TUB and the lack of the control bands for the KATG and INHA gene loci.
LPA_FQ_failure: LPA FQ failure; sample that failed to provide a result for FQ. "Passed" indicates a successful result for FQ , while "Target failure" indicates a failed results for FQ due to the absence TUB and the lack of the control bands for the GYRA abd GYRB gene loci.
LPA_AMK_failure: LPA AMK failure; sample that failed to provide a result for AMK. "Passed" indicates a successful result for AMK , while "Target failure" indicates a failed results for AMK due to the absence TUB and the lack of the control bands for the RRS abd EIS gene loci.

Access information

Other publicly accessible locations of the data:

Human subjects data

This publicly available metadata dataset has been de-identified to ensure the protection of human subjects in accordance with international ethical standards and applicable data protection regulations, including but not limited to the U.S. Health Insurance Portability and Accountability Act (HIPAA), the EU General Data Protection Regulation (GDPR), and relevant local laws in participating countries.

All direct identifiers (e.g., names, dates of birth, addresses, contact information) have been removed. Indirect identifiers have also been reviewed and excluded or generalized to prevent re-identification of individuals. No data fields in the public release, either alone or in combination, can reasonably be used to identify a subject. Additionally, there are no retained keys, codes, or linkable information that would allow re-identification of the de-identified dataset by users.

This de-identification process has been conducted under the oversight of qualified personnel and in compliance with institutional and regulatory guidelines. As such, the dataset is not considered to involve human subjects and is suitable for unrestricted public dissemination and secondary analysis.