Novel Sequencing Tool Provides First Accurate Tuberculosis Genome

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Scanning electron micrograph of M. tuberculosis. Credit: Janice Carr/CDC

Key Points:

  • Researchers have created a new genome assembly tool for TB.
  • The tool assembles genomes without a reference using data from MinION sequencers.
  • The TB sequence created by the pipeline contains 6,400 thousand more pieces of information than the old reference.

Researchers from Rutgers New Jersey Medical school have developed a new genome assembly tool that could spur the development of new treatments for tuberculosis and other bacterial infections. Even better, the new tool—which has created an improved genome map of one tuberculosis strain—should do the same for other strains and other types of bacteria.

“The key to beating this disease is to understand it, and the key to understanding it lies in its DNA,” said senior author David Alland, chief of the Division of Infectious Diseases at Rutgers New Jersey Medical School. “We hope our new pipeline provides researchers around the world with the information they need to create faster, more effective treatments and, ideally, a fully effective vaccine.”

The new pipeline, dubbed Bact-Builder, combines common open-source genome assembly programs into a novel and easy-to-use tool which is freely available on GitHub.

Scientists first sequenced the genome of the H37Rv strain of TB in 1998, but researchers were unable to generate the complete and accurate sequence needed to maximize their chances of eradicating the disease. Today, scientists typically cut large pieces of DNA into small, quick-to-scan fragments, and then use a reference sequence—such as H37Rv—to align all the resulting pieces of data properly.

Bact-Builder, however, assembles genomes without a reference using data from MinION sequencers. This allows researchers to identify genes present in clinical strains that may not be present in the reference.

The tuberculosis sequence created by Bact-Builder contains 6,400 thousand more pieces of information (base pairs) than the old reference and identifies new genes and gene fragments.

Alland says having an easy way to sequence all TB strains accurately is critical movin forward.

“Strain comparison should answer many vital questions, such as why some strains are more contagious than others. Why do some strains cause more serious disease? Why are some strains more difficult to cure? The answers to all these questions, which could help us devise better treatments and vaccines, are in the genetic code, but you need an accurate way to find them,” said Alland.

 

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