️ Episode 247: Genome graphs reveal structural variation in M. tuberculosis

In this episode of PaperCast Base by Base, we explore Long-read assemblies and a pangenome reference graph uncover widespread structural variants that shape Mycobacterium tuberculosis evolution and contribute to drug resistance

Study Highlights:
The authors built an M. tuberculosis pangenome reference graph from 859 high-quality long-read assemblies and identified 3,077 unique structural variants genome-wide. They developed miniwalk to genotype SVs from graph-mapped assemblies and showed higher precision for short-read SV genotyping (0.7 vs 0.46 for manta) at modest cost to recall. SVs cluster in GC-rich PE/PPE regions and include recurrent events such as a ppe25-ppe27 deletion fixed in L4.4 and diverse deletions of the copper exporter ctpV specific to sub-lineage L1.2.1 that alter copper-associated transcription. Genotyping 41,134 isolates revealed non-canonical SVs and SV-gene burdens associated with resistance to multiple first- and second-line drugs

Conclusion:
Structural variants are an important and previously underappreciated driver of M. tuberculosis evolution and drug resistance, and pangenome graph approaches improve their detection

Music:
Enjoy the music based on this article at the end of the episode.

Reference:
Canalda-Baltrons A., Theys D., Chang X., Viberg L. T., Sherry N. L., Coin L., Dunstan S. J., Silcocks M., Hall M. B. Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance. Nature Communications. 2025;16:10 746. https://doi.org/10.1038/s41467-025-65779-9

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.castos.com/episodes/structural-variation-mtb-pangenome

Episode Slug: structural-variation-mtb-pangenome

Keywords: structural variation, pangenome graph, Mycobacterium tuberculosis, drug resistance, long-read sequencing