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A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome.

Poonam ChitaleAlexander D LemenzeEmily C FogartyAvi ShahCourtney GradyAubrey R Odom-MaybeW Evan JohnsonJason H YangA Murat ErenRoland BroschPradeep KumarDavid Alland
Published in: Nature communications (2022)
H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is globally used as the M. tuberculosis reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete and accurate bacterial genome sequences and apply it to three independently cultured and sequenced H37Rv aliquots of a single laboratory stock. Two of the 4,417,942 base-pair long H37Rv assemblies are 100% identical, with the third differing by a single nucleotide. Compared to the existing H37Rv reference, the new sequence contains ~6.4 kb additional base pairs, encoding ten new regions that include insertions in PE/PPE genes and new paralogs of esxN and esxJ, which are differentially expressed compared to the reference genes. New sequencing and de novo assemblies with Bact-Builder confirm that all 10 regions, plus small additional polymorphisms, are also present in the commonly used H37Rv strains NR123, TMC102, and H37Rv1998. Thus, Bact-Builder shows promise as an improved method to perform accurate and reproducible de novo assemblies of bacterial genomes, and our work provides important updates to the primary M. tuberculosis reference genome.
Keyphrases
  • mycobacterium tuberculosis
  • pulmonary tuberculosis
  • genome wide
  • machine learning
  • big data
  • hepatitis c virus
  • hiv infected
  • hiv aids
  • human immunodeficiency virus
  • mass spectrometry