The Rapid Drug Susceptibility Testing Consortium (RDST), coordinated by the Critical Path Institute (C-Path) through the Critical Path to TB Drug Regimens (CPTR) initiative, has launched the Relational Sequencing TB data platform (ReSeqTB). ReSeqTB is a data-sharing platform and analytic visualization tool that can be used to discover, grade, and track key bacterial drug-resistance mutations. The tool was created to facilitate the development of new diagnostics capable of rapidly testing drug susceptibility, which could be used to identify effective treatment regimens for better managing patients with drug-resistant tuberculosis (TB).

One of the targets of the United Nations’ sustainable development goals for 2030 is to end the TB epidemic, which demands a global effort to tackle the rise of multidrug-resistant TB (MDR-TB). Approximately 52% of MDR-TB patients are successfully treated, compared to more than 80% of patients with drug-susceptible TB.1

Current approaches to test for drug susceptibility require trained technical support and well-resourced laboratories. It can take several months to deliver results, especially if the Mycobacterium tuberculosis (M.tb) bacteria are resistant and require testing against an expanded panel of drugs. ReSeqTB was developed to change the paradigm by enabling clinicians and researchers to identify mutations to all drugs simultaneously.

ReSeqTB provides researchers with a user-friendly interface to access whole-genome sequencing data that is standardized, collated, and integrated with culture-based drug susceptibility tests, incorporating clinical outcome data when available. This resource is intended to provide a one-stop location for such stakeholders as healthcare professionals, researchers, and diagnostic developers to identify and categorize M.tb mutations associated with drug resistance. Identifying drug-resistance mutations using genomic-based diagnostic assays can facilitate quick, well-tailored delivery of patient care. The ReSeqTB platform will help overcome confusion about the relevance of mutations and their clinical interpretation. This will be particularly important as new TB treatments are approved and scaled up.

“The ReSeqTB platform provides TB research efforts—specifically for TB surveillance using sequencing technologies—with standardized criteria for grading TB drug-resistance conferring mutations through a validated algorithm,” says Matteo Zignol, MD, MPH, scientist at the TB monitoring and evaluation section of the World Health Organization (WHO) global TB program.

ReSeqTB is now open to researchers outside of CPTR, who can request access to the data platform via the ReSeqTB website. Expanded access will drive additional research across multiple segments, which can improve treatment practices and increase the efficiency of TB research. To date, more than 2,000 users have visited the ReSeqTB website.

“The goal of opening ReSeqTB more widely is to promote public access to new and contemporary curated data that has been aggregated from different TB studies under a common clinical data interchange standards consortium standard,” says Marco Schito, PhD, scientific director at CPTR. “A tiered access system will be used to allow individual contributors to define data use and timing of access. This will accelerate the identification and validation of mutations associated with resistance to existing, new, and repurposed drugs, and is in line with funders’ requests to ensure publicly funded data are effectively disseminated to promote further collaboration.”

The ReSeqTB platform is user-focused. It features a visual browser to aid in the identification and analysis of mutations and their correlation with drug resistance and susceptibility. Downloadable drug-resistance reports, along with visualization tools, are available and will be further optimized based on user feedback. More mutations will be validated as data are contributed to the platform. Additional tools and enhancements will be introduced on an ongoing basis.

The continued development of ReSeqTB requires ongoing interaction and dialogue with stakeholders on needs, requirements, and data-sharing challenges. Future iterations of the platform will reflect feedback from clinicians, national TB programs, and patient advocacy groups.

ReSeqTB is a joint initiative funded by the Bill & Melinda Gates Foundation, with extensive contributions from several partner organizations, including C-Path and CPTR, FIND, WHO, the Stop TB Partnership’s new diagnostics working group, and the US Centers for Disease Control and Prevention.

Cofounded by the Bill and Melinda Gates Foundation, the Critical Path Institute, and the TB Alliance, and launched in March 2010, CPTR is working with stakeholders around the world to advance a new paradigm that dramatically speeds new TB drug regimens to patients.

For more information, visit the Critical Path Institute.

REFERENCE

  1. Global Tuberculosis Report, 2016. Geneva, Switzerland: World Health Organization, 2016. Available at: apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed February 13, 2017.