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Ng, KCS, Ngabonziza, JCS, Lempens, P, de Jong, BC, van Leth, F and Meehan, CJ 
ORCID: https://orcid.org/0000-0003-0724-8343,
2019.
Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data.
PeerJ, 7: e7564.
ISSN 2167-8359
Abstract
Background: Mycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicin-resistant (RR)-TB. However, as next-generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low- and middle-income high TB-burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance.
Methods: We developed the Python-based MycTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs—Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data.
Results: The MTBGT tool correctly transformed the single nucleotide polymorphism (SNP) data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin-susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda.
Conclusion: Overall, the MTBGT tool allows low- and middle-income countries to make sense of the increasingly generated WGS in light of the readily available RDT results, and assess whether currently implemented RDTs adequately detect RR-TB in their setting. With its feature to transform WGS to RDT results and facilitate continuous RR-TB data analysis, the MTBGT tool may bridge the gap between and among data from periodic surveys, continuous surveillance, research, and routine tests, and may be integrated within the national information system for use by the NTP and epidemiologists to improve setting-specific RR-TB control. The MTBGT source code and accompanying documentation are available at https://github.com/KamelaNg/MTBGT.
| Item Type: | Journal article |
|---|---|
| Publication Title: | PeerJ |
| Creators: | Ng, K.C.S., Ngabonziza, J.C.S., Lempens, P., de Jong, B.C., van Leth, F. and Meehan, C.J. |
| Publisher: | PeerJ |
| Date: | 26 August 2019 |
| Volume: | 7 |
| ISSN: | 2167-8359 |
| Identifiers: | Number Type 10.7717/peerj.7564 DOI 1627051 Other |
| Rights: | This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Jonathan Gallacher |
| Date Added: | 13 Dec 2022 08:33 |
| Last Modified: | 13 Dec 2022 08:33 |
| URI: | https://irep.ntu.ac.uk/id/eprint/47633 |
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