PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data

Abstract

Antibiotic-resistant tuberculosis poses a global threat, causing the deaths of hundreds of thousands of people annually. While whole-genome sequencing (WGS), with its unprecedented level of detail, promises to play an increasingly important role in diagnosis, data analysis is a daunting challenge. Here, we present a simple-to-use web service (free for academic use at http://phyresse .org). Delineating both lineage and resistance, it provides state-of-the-art methodology to life scientists and physicians untrained in bioinformatics. It combines elaborate data processing and quality control, as befits human diagnostics, with a treasure trove of validated resistance data collected from well-characterized samples in-house and worldwide.

Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

“…Web-based tools capable of analyzing WGS data of MTBC for the purposes of genotyping and drug resistance profiling have become available, including PhyResSe and TGS-TB, among others (42,43). Two such platforms, TB-Profiler and MUBII-TB-DB, were compared for their success at predicting resistance to the major TB drugs (44).…”

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

“…Extracted DNA was frozen at NCTLD until shipment to Emory University, where whole-genome sequencing was performed using an Illumina HiSeq 2000 instrument. The FastQ sequencing files for all M. tuberculosis isolates were uploaded to the Phylo-Resistance Search Engine (PhyResSE; http://phyresse.org, accession numbers 593375378609f78d466ecec7ceff6768 and 75ba5a7139084e9f061875f303b6d822), which is a web-based tool to delineate the M. tuberculosis antibiotic resistance and lineage from whole-genome sequencing data (28).…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…145,146 However, before wholegenome sequencing information can be used in routine clinical practice, several important issues need to be resolved. Whole-genome sequencing is complicated by the need for culture before DNA extraction, 147 incomplete knowledge of all resistance-conferring mutations, 59,148 and the need for a validated pipeline to accurately predict resistance. 149 A relational sequencing tuberculosis data platform (ReSeqTB) is being developed in a partnership between the Foundation for Innovative Diagnostics and Critical Path to TB Drug Regimens to catalogue genotypic and phenotypic data and to provide a validated pipeline for the analysis of whole-genome sequencing.…”

“…128 However, as described by the routine strain typing service in the UK, the effect of molecular epidemiological data on patient care and public health response might not be useful if those data are not reported and acted upon quickly. 153 To achieve this, major technical and systems barriers must be overcome, including the strengthening of information technology systems to facilitate timely capture, export, and potentially automated analysis of complex data, such as in web-based systems; 148 linking molecular data to key epidemiological data (eg, geographical location); improving local scientific capacity; and providing decision makers with sufficient autonomy and resources to act in response to such data.…”