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World Database: Tuberculosis

  • 10 Jun 2021 07:55
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The Gates Foundation has awarded the Arizona based Critical Path Institute a three-year, $3 million grant to create a catalogue of tuberculosis genomes from around the world. The database will inform correlations between bacterial genetic mutations, phenotypic information about drug susceptibility, and patient outcomes used to accelerate diagnostic test development helping clinicians treat TB strains more effectively on a global scale.

"There is a huge need for rapid drug susceptibility tests to make sure patients get the right treatment on first dose. We have some new drugs and new drug regimens in the pipeline for TB patients. We are trying to aggregate all the quality information to inform assay development," Debra Hanna, executive director of the TB Drug Regimen Initiative at Critical Path , told GenomeWeb. "We need to speed up the diagnosis of resistance profiles of TB isolates and determine what, specifically, these isolates are resistant to."

Hanna highlighted the HIV drug resistance database  developed by Stanford University as a model Critical Path would like to emulate for the TB database. "We need to be even more global in nature. We need to make sure isolates in our platform are representative of the countries where TB is most endemic," she says. 

"There is no mandate that researchers contribute to the database, but there is a really compelling value proposition to do so. They have generated this important data; if we can bring it all together, their information can be used to inform new and exciting assays and treatments."

"We will have big outreach campaign do our very best to target all the labs that we think have important data to contribute. We will leverage the network of our leadership team and we have processes being developed to upload those data into the database."

As part of the Initiative, Critical Path organisation is working with expert partners including WHO(World Health Organisation), US Centers for DCP (Disease Control and Prevention), NIH (National Institutes of Health) and Gates Foundation to ensure the quality of incoming data. A parallel grant of about the same size from Gates Foundation  went to FIND Diagnostics, a non-profit foundation, in order to help create the expert partnership.

Accelerating the development of more sensitive and more specific assays, that can make use of sequencing technology, is a particular priority for Critical Path,  Hanna says. The current standard of care involves phenotypic testing of how drugs inhibit growth of a particular TB strain. "It's important to marry what's happening in the genome to what's happening in the phenotypic space," she said.

The consortium is already partnered with several molecular diagnostics firms along with researchers who will contribute data. In the eighteen months, several molecular diagnostic firms and research organisations besides FIND have signed as consortium partners, as Abbott Molecular, Alere, BioMérieux, Cepheid, Epistem, Johnson & Johnson's Janssen Biotech, Sanofi-Aventis, the PATH, the TB Alliance, and Treatment Action Group. 

The Critical Path team hopes to be able to give access to early data contributors and consortium partners. Part of the grant's mandate is data will eventually be made available to the global community. Hanna said the complexity of the project stems more from the data management challenges than software.

"A really important piece of the project is bringing together the right subject matter expertise and advisory input," she said. "We need to evaluate what should come into this database to ensure that what's in the database will inform assay development."

The quality of phenotypic data will be a major challenge, due to differences in many existing methods used to test drug susceptibility.


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