theDahunsiDavid/mtb-drug-resistance-pipeline

WGS-based drug resistance profiling and lineage classification of 15 Mycobacterium tuberculosis isolates from South Africa using TB-Profiler and Python. # Drug Resistance Profiling of _Mycobacterium tuberculosis_ Genomes This project provides a reproducible bioinformatics pipeline for whole-genome sequencing (WGS)-based drug resistance profiling and lineage classification of _Mycobacterium tuberculosis_ (MTB) isolates from South Africa. --- ## Background Tuberculosis (TB), caused by _Mycobacterium tuberculosis_ (MTB), is the world's leading cause of death from a single infectious agent. It was also the leading killer of people with HIV in 2024 [1]. Unfortunately, 69% of all HIV-associated TB cases in the world occur in the African Region, with South Africa being heavily affected [2]. It takes a standard 6-month regimen to treat drug-susceptible TB. However, mutations in certain MTB genes are fueling the emergence of drug-resistant TB. First-line drugs are ineffective against drug-resistant TB, so clinicians have to resort to later-generation drugs that are more expensive and toxic [3]. Additionally, treatment with these later-generation drugs can take up to 18–24 months [2]. Diagnosing TB is another hurdle. TB is an airborne disease, but it develops slowly. Traditional solid media culturing (in the lab) takes 4–6 weeks. Identifying which drugs a cultured isolate is resistant to also adds more weeks to the timeline [4]. Fortunately, recent progress in computational genomics offers a faster alternative. Whole-genome sequencing (WGS) of MTB, along with bioinformatics tools like TB-Profiler, makes it easier to comprehensively profile resistance directly from a cultured isolate. These tools can also do lineage classification and variant-level resolution of resistance mechanisms [5]. For this project, samples were drawn from BioProject PRJNA1256480 (B-Prepared, Columbia University), a whole-genome sequencing dataset of South African TB isolates deposited in April 2025 [6]. No associated publication was available at the time of analysis. --- ## Pipeline Overview The pipeline consists of six sequential steps: …