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Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis

Mariner-Llicer, C.; Goig, G. A.; Torres-Puente, M.; Vashakidze, S.; Villamayor, L.; Saavedra-Cervera, B.; Mambuque, E.; Khurtsilava, I.; Avaliani, Z.; Rosenthal, A.; Gabrielian, A.; Shurgaia, M.; Shubladze, N.; Garcia-Basteiro, A. L.; Lopez, M.; Comas, I.

2024-01-31 genomics
10.1101/2024.01.30.577772 bioRxiv
Show abstract

Culturing Mycobacterium tuberculosis (MTB) from tuberculosis cases is the basis for many research and clinical applications. Paradoxically, it is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. The alternative, culture-free sequencing from diagnostic samples, is a promising but challenging approach both to obtain and analyse the MTB genome from the complex sample. This study obtains high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics pipeline. Our approach reveals that 88% of variants called in culture-free sequencing analysis are false positives due to supplementary alignments, mostly in enriched-sputa samples. Overall, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants frequency (0.98). Our findings extrapolate to all publicly available data, thus demonstrating that in most cases culture accurately mirrors clinical samples.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.