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Critical Path Receives $3M Gates Foundation Award for TB Genome Database

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NEW YORK (GenomeWeb) – The Bill and Melinda Gates Foundation has awarded the Critical Path Institute a three-year, $3 million grant to create a catalog of tuberculosis genomes from around the world. The database will inform correlations between bacterial genetic mutations, phenotypic information about drug susceptibility, and patient outcomes that will be used to accelerate the development of diagnostic tests to help clinicians more effectively treat TB strains 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."

Tuscon, Ariz.-based Critical Path will use the money to develop a software platform to aggregate whole genome data on TB strains that is currently scattered and siloed in data repositories around the world at academic institutions, global surveillance repositories, and in national databases. The software platform will combine genomic data along with phenotypic data about drug susceptibility and data on patient outcomes, when available.

"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," Hanna said.

The organization has developed software and data infrastructure to house clinical trial data for TB drug therapies and will expand on that, building a platform that can incorporate whole genome sequence-level data. It will also likely develop software tools to analyze the database, but will look to incorporate existing, easy-to-use data tools to help facilitate global accessibility.

As part of the Critical Path to TB Drug Regimens Initiative, the organization is working with expert partners including the World Health Organization, the US Centers for Disease Control and Prevention, the National Institutes of Health, and the Gates Foundation to ensure the quality of incoming data. A parallel grant from the Gates Foundation of about the same size went to FIND Diagnostics, a non-profit foundation, 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 said. 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," Hanna said.

The consortium has already partnered with several molecular diagnostics firms who will be given first access to the database, along with researchers who will contribute data. In the last year and half, several molecular diagnostic firms and research organizations besides FIND have signed on as consortium partners, including Abbott Molecular, Alere, BioMérieux, Cepheid, Epistem, Johnson & Johnson's Janssen Biotech, Sanofi-Aventis, the PATH, the TB Alliance, and the Treatment Action Group. The consortium is currently in discussion with other firms to join as partners.

The Critical Path team has already been working on the new platform for several months, with at least eight people devoted to the project. By the end of the first year, it hopes to be able to give access to early data contributors and consortium partners, but as part of the grant's mandate, data will eventually be made available to the global community. Critical Path will make the database more accessible to other end users like clinicians and the broader research community as the project progresses, using the CPTR web portal, Hanna said.

Though Critical Path has not yet developed any software that stores genomic data, Hanna said the complexity of the project stems more from the data management challenges.

"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 particular challenge, due to the differences in the many existing methods used to test drug susceptibility.

Hanna points to 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 said. "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."

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