Nature sub-issue: New assembly tool leads to more accurate Mycobacterium tuberculosis genome

Researchers at Rutgers University's New Jersey School of Medicine have developed a new genome assembly tool that promises to help researchers design new treatments to tackle tuberculosis and other bacterial infections
.

The study was published in the journal Nature Communications
.
The researchers say they have used the new tool to improve the genome map of one strain of tuberculosis, and it can also be applied to other strains and other types of bacteria
.

According to the World Health Organization, Mycobacterium tuberculosis (M.
tuberculosis).
Tuberculosis) infected about a quarter of the world's population and killed 1.
6 million people in 2021
.
For TB, current medical interventions are limited to a century-old vaccine that reduces the risk of infection by 20%, while strong antibiotics are used for four to six months but sometimes do not work
.

David Alland, senior author of the study and director of the Division of Infectious Diseases at Rutgers Medical College of New Jersey, said: "The key to defeating this disease is to understand it, and the key to understanding it is to understand its DNA
.
We hope that our new process will give researchers around the world the information they need to create faster, more effective treatments, preferably a fully effective vaccine
.
" ”

Back in 1998, scientists first sequenced the genome of the TB strain H37Rv, but until now, they have not been able to produce a complete and accurate genome sequence that would maximize the elimination of the disease
.

In order to solve the sequencing problem of Mycobacterium tuberculosis H37Rv, the researchers have developed a new process to generate highly accurate whole genome sequences
by de-novo assembly method.
The new tool, named Bact-Builder, uses an assembly method based on long-read long-term common sequences and is applied to
three independently cultured H37Rv cultures.

Nowadays, when sequencing new bacterial genomes, it is common to break long DNA fragments into small fragments that can be scanned quickly, and then assemble all the resulting data correctly using a reference sequence such as H37Rv
.
However, Bact-Builder used long-read, long-read data generated by the MinION sequencer to assemble the genome without a reference, which could help researchers identify genes
that only exist in clinical strains.

The Mycobacterium tuberculosis sequences obtained by the Bact-Builder construction have about 6.
4 kb more new sequences than the old reference data, and more importantly, it can identify new genes and gene fragments
that are missing from the old reference data.

"Reference sequences for the H37Rv strain are used in hundreds of studies each year, and just publishing the exact genome of the reference strain can go a long way in TB research," Alland said
.

Alland believes that it is even more important to have a simple way to accurately sequence all strains, "because strain comparison can answer many important questions, such as why are some strains more contagious?" Why do some strains cause more severe disease? Why are some strains harder to cure? The answers to all of these questions are in the genetic code, and they can help us design better treatments and vaccines, but you need an accurate way to find them
.
”

Original search

Chitale, P.
, Lemenze, A.
D.
, Fogarty, E.
C.
et al.
A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome.
Nat Commun 13, 7068 (2022).
https://doi.
org/10.
1038/s41467-022-34853-x