Analytical concordance of targeted next-generation sequencing and whole-genome sequencing for Mycobacterium tuberculosis drug resistance and lineage determination in West Java, Indonesia

Timely detection of drug-resistant tuberculosis (DR-TB) cases is crucial for effective treatment and limiting transmission. This study examined the performance of targeted next-generation sequencing (tNGS) compared to whole-genome sequencing (WGS) for identifying drug resistance in rifampicin-resistant TB samples from West Java, Indonesia.

The researchers used the Deeplex Myc-TB tNGS assay and performed both WGS and tNGS on 116 prospectively-collected samples using the Illumina MiSeq platform. Both sequencing methods showed high concordance across thirteen anti-TB drugs, particularly for those in the BPaLM regimen. However, 31.03% of samples (n=36) had discrepant resistance calling between the two methods, with 73 discordant variants identified.

The primary source of discrepancy was when tNGS detected a resistance-conferring mutation that WGS did not, occurring in 54.8% of cases. tNGS was better at detecting mixed infections, while WGS provided a more detailed understanding of the Mycobacterium tuberculosis lineage. tNGS showed good concordance with WGS in identifying resistance-conferring mutations, with the added advantage of a faster turnaround time.

Continuous updates to the tNGS panel and mutation catalogue are necessary to maintain the tool's clinical relevance.