6 hasil untuk "Samuel J. Modlin"
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Artikel Jurnal
SMRT genome assembly corrects reference errors, resolving the genetic basis of virulence in Mycobacterium tuberculosis
Abstract Background The 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…
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Artikel Jurnal
Interred mechanisms of resistance and host immune evasion revealed through network-connectivity analysis of M. tuberculosis complex graph pangenome
ABSTRACT Mycobacterium tuberculosis complex successfully adapts to environmental pressures through mechanisms of rapid adaptation which remain poorly understood despite knowledge gained through decades of research. In this study, we used 110 reference-quality, complete de novo assembled, long-read…
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Artikel Jurnal
Updated Erdman reveals tandem repeat copy number is phase-variable and impacts M. tuberculosis adaptation across evolutionary timescales
ABSTRACT High-quality reference genomes are essential for comparative genomics and accurate genotype-phenotype mapping. Here, we corrected the Mycobacterium tuberculosis Erdman strain reference genome (ErdmanTI) using ultra-deep HiFi sequencing. Among the small variants (n = 275) between ErdmanTI…
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Artikel Jurnal
Pyrazinamide Susceptibility Is Driven by Activation of the SigE-Dependent Cell Envelope Stress Response in Mycobacterium tuberculosis
ABSTRACT Pyrazinamide (PZA) plays a crucial role in first-line tuberculosis drug therapy. Unlike other antimicrobial agents, PZA is active against Mycobacterium tuberculosis only at low pH. The basis for this conditional drug susceptibility remains undefined. In this study, we utilized a…
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Artikel Jurnal
Structure-Aware Mycobacterium tuberculosis Functional Annotation Uncloaks Resistance, Metabolic, and Virulence Genes
ABSTRACT Accurate and timely functional genome annotation is essential for translating basic pathogen research into clinically impactful advances. Here, through literature curation and structure-function inference, we systematically update the functional genome annotation of Mycobacterium…
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Artikel Jurnal
Drivers and sites of diversity in the DNA adenine methylomes of 93 Mycobacterium tuberculosis complex clinical isolates
This study assembles DNA adenine methylomes for 93 Mycobacterium tuberculosis complex (MTBC) isolates from seven lineages paired with fully-annotated, finished, de novo assembled genomes. Integrative analysis yielded four key results. First, methyltransferase allele-methylome mapping corrected…