On March 24, 2025-World TB Day-Union Minister Dr. Jitendra Singh announced at Vigyan Bhawan, New Delhi, that India has completed whole genome sequencing (WGS) of 10,000 Mycobacterium tuberculosis isolates.

This is a big step under the "Dare2eraD TB" initiative, led by the Department of Biotechnology (DBT), in collaboration with the Council of Scientific and Industrial Research (CSIR) and the Indian Council of Medical Research (ICMR).

The Indian Tuberculosis Genomic Surveillance Consortium (InTGS) is driving this effort, with a target of sequencing 32,500 samples by November 2025.

Nine labs across these organizations are involved, aiming to map the genetic diversity of TB strains and tackle drug resistance-a growing threat in India.

TB in India isn't just a numbers game; it's a complex beast with multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains complicating treatment. Of the 10,000 samples sequenced so far, about 7% showed resistance to a single drug, hinting at the scale of the problem. The goal here is to use WGS to:

• Spot Drug Resistance Early: Traditional diagnostics like sputum smears or even Xpert MTB/RIF take weeks and miss some resistance patterns. WGS can detect mutations linked to resistance against 18+ anti-TB drugs in days-or even hours with optimized setups.
• Understand Strain Diversity: India's TB strains vary regionally (e.g., Lineage 3 dominates in the north, per some studies). Sequencing reveals these patterns, aiding targeted interventions.
• Boost Precision Medicine: By linking mutations to treatment outcomes, doctors can skip the trial-and-error phase and prescribe effective drugs faster.

This isn't India's first foray into TB genomics. Earlier efforts, like sequencing 200 isolates from North India (2010-2014) or 223 from Southern India (published 2017), showed genetic heterogeneity and novel resistance mutations not caught by standard tests. For instance, a North India study found 343 novel single nucleotide variants (SNVs) in drug-resistance genes, ignored by current diagnostic kits.

• Sample Collection: Isolates come from active TB patients across India-pulmonary and extrapulmonary cases alike. The InTGS consortium, spanning eight states, has 10 sites collecting samples.
• Sequencing Tech: Illumina platforms (like MiSeq) are the workhorse here, though some projects (e.g., in Mumbai) explore faster options like Oxford Nanopore for real-time results.
• Analysis: AI and machine learning crunch the data, correlating mutations with resistance patterns. For example, common mutations like Ser315Thr (in inhA) or Ser450Leu (in rpoB) flag isoniazid and rifampicin resistance, respectively.

Take Mumbai's WGS project at KEM Hospital, launched in 2023. It targets 2,500 MDR-TB patients, cutting diagnosis time from weeks to hours. Of 600 clinical samples sequenced in a 2024 study, 51% were pre-XD-resistant to rifampicin and fluoroquinolones-highlighting a brewing crisis.

Nationally, the 10,000 sequenced isolates show emerging resistance to newer drugs like bedaquiline (1% of cases) and linezolid (7.5%), signaling a need for tighter drug stewardship.

• Scale: 10,000 is a fraction of India's TB cases. With 135,000 MDR cases estimated in 2020, 32,500 sequenced samples by late 2025 still won't cover the full spectrum.
• Access: WGS is lab-heavy and costly (around €217 per sample in some settings, excluding staff costs). Rolling it out beyond research to rural clinics is a pipe dream for now.
• Data Gaps: Phenotypic data (how strains behave in patients) lags behind genomic data, muddying validation. Plus, latent TB-potentially 3,000 per million-stays under the radar.