ArticleBMC genomics2017
SMRT genome assembly corrects reference errors, resolving the genetic basis of virulence in Mycobacterium tuberculosis.
Article in BMC genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Pervasive genome structure heterogeneity iniScience · 2026Article
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- Interred mechanisms of resistance and host immune evasion revealed through network-connectivity analysis ofmSystems · 2025Article
- High-Accuracy Long-Read Sequencing ofThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Article
- Intercellular mosaic methylation in fast-growingNAR molecular medicine · 2024Article
- Functional genetic variation inFrontiers in microbiology · 2023Article
- Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study.Antimicrobial agents and chemotherapy · 2022Article
- Patterns of genomic interrelatedness of publicly available samples in the TB portals database.Tuberculosis (Edinburgh, Scotland) · 2022Article
- Article
- A complete high-quality MinION nanopore assembly of an extensively drug-resistant Mycobacterium tuberculosis Beijing lineage strain identifies novel variation in repetitive PE/PPE gene regions.Microbial genomics · 2018Article
- Integrated Multi-Omic Analysis ofFrontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
backgroundThe genetic basis of virulence in Mycobacterium tuberculosis has been investigated through genome comparisons of virulent (H37Rv) and attenuated (H37Ra) sister strains. Such analysis, however, relies heavily on the accuracy of the sequences. While the H37Rv reference genome has had several corrections to date, that of H37Ra is unmodified since its original publication.
resultsHere, we report the assembly and finishing of the H37Ra genome from single-molecule, real-time (SMRT) sequencing. Our assembly reveals that the number of H37Ra-specific variants is less than half of what the Sanger-based H37Ra reference sequence indicates, undermining and, in some cases, invalidating the conclusions of several studies. PE_PPE family genes, which are intractable to commonly-used sequencing platforms because of their repetitive and GC-rich nature, are overrepresented in the set of genes in which all reported H37Ra-specific variants are contradicted. Further, one of the sequencing errors in H37Ra masks a true variant in common with the clinical strain CDC1551 which, when considered in the context of previous work, corresponds to a sequencing error in the H37Rv reference genome.
conclusionsOur results constrain the set of genomic differences possibly affecting virulence by more than half, which focuses laboratory investigation on pertinent targets and demonstrates the power of SMRT sequencing for producing high-quality reference genomes.
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