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    Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data

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    Meehan_PeerJ (2.175Mb)
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    Publication date
    2019-08
    Author
    Ng, K.C.S.
    Ngabonziza, J.C.S.
    Lempens, P.
    de Jong, B.C.
    van Leth, F.
    Meehan, Conor J.
    Keyword
    Mycobacterium tuberculosis
    Rifampicin-resistant tuberculosis
    Xpert MTB/RIF
    XpertMTB/RIF Ultra
    GenoType MDRTBplus v2.0
    GenoscholarNTM+MDRTB II
    Python
    Next generation sequencing
    Whole genome sequences
    Single nucleotide polymorphism
    Rights
    © 2019 Ng et al. Distributed under Creative Commons CC-BY 4.0
    Peer-Reviewed
    Yes
    
    Metadata
    Show full item record
    Abstract
    Background: Mycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicinresistant (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.
    URI
    http://hdl.handle.net/10454/17491
    Version
    Published version
    Citation
    Ng KCS, Ngabonziza JCS, Lempens P et al (2019) Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data. PeerJ. 7:e7564.
    Link to publisher’s version
    https://doi.org/10.7717/peerj.7564
    Type
    Article
    Collections
    Life Sciences Publications

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