Evaluation of the application value of the whole genome sequence analysis tools, TB Profiler v2.8.0, Mykrobe v0.7.0 and PhyResSE v1.0, in testing drug-resistant tuberculosis

doi:10.3969/j.issn.1000-6621.2020.11.010

Abstract

Abstract:

Objective To evaluate the application of three whole genome sequence (WGS) analysis tools developed for Mycobacterium tuberculosis (MTB), TB Profiler v2.8.0, Mykrobe v0.7.0 and PhyResSE v1.0, in testing drug-resistant of tuberculosis. Methods WGS data and drug susceptibility testing (DST) results of 534 MTB clinical isolates from two previous studies were collected from National Center for Biotechnology Information Sequence Read Archive (NCBI SRA) database. Of the 534 MTB clinical isolates, 457 were multi-resistant and 77 were susceptible. Using DST as reference, WGS data were analyzed by TB Profiler, Mykrobe and PhyResSE to access the performance on predicting resistance to first-line and second-line anti-tuberculosis drugs. Results Taking DST results as reference, the sensitivities of TB Profiler, Mykrobe and PhyResSE for rifampicin resistance were similar, which were 90.81% (415/457), 87.75% (401/457) and 90.81% (415/457), respectively. The sensitivities of Mykrobe and PhyResSE for isoniazid resistance were 76.42% (350/458) and 76.20% (349/458), slightly higher than that of TB Profiler (69.43%, 318/458). The sensitivities of the three tools for ethambutol and streptomycin resistance were similar, ranging from 76.00% to 81.61%. As to pyrazinamide, the sensitivity of TB Profiler (72.82%, 150/206) was higher than those of Mykrobe (61.65%, 127/206) and PhyResSE (50.97%, 105/206). For fluoroquinolones and amikacin, the sensitivities of PhyResSE were 88.27% (143/162) and 60.00% (27/45), higher than those of TB Profiler (81.48% (132/162) and 48.89% (22/45)) and Mykrobe (82.10% (133/162) and 55.56% (25/45). The specificities of the three tools for detecting drug resistance of anti-tuberculosis drugs were similar and high (higher than 90%), except for ethambutol which was 82.42%-83.88%. Conclusion All of the three bioinformatics tools have a good performance on rapid detection of drug-resistant tuberculosis with a promising prospect of future application. The relatively low sensitivity of the tools to pyrazinamide and some second-line anti-tuberculosis drugs suggests that studies on resistance mechanism of these drugs should be enhanced.

Key words: Mycobacterium tuberculosis, Genome-wide sequencing, Diagnosis, Drug resistance

LI Bing-ying, ZHENG Xu-bin, HU Yi, XU Biao. Evaluation of the application value of the whole genome sequence analysis tools, TB Profiler v2.8.0, Mykrobe v0.7.0 and PhyResSE v1.0, in testing drug-resistant tuberculosis[J]. Chinese Journal of Antituberculosis, 2020, 42(11): 1196-1202. doi: 10.3969/j.issn.1000-6621.2020.11.010

Figures/Tables 4

References 20

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分析工具	一线抗结核药品				二线抗结核药品
分析工具	INH	RFP	PZA	EMB	FQ	Bdq	Lzd	Cfz	Am	Sm	Eto	PAS
TB Profiler	√	√	√	√	√	√	√	√	√	√	√	√
Mykrobe	√	√	√	√	√	-	-	-	√	√	-	-
PhyResSE	√	√	√	√	√	-	-	-	√	√	√	-

性能	TB Profiler	Mykrobe	PhyResSE
工具版本	网页版和命令行版本	独立软件和命令行版本	网页版
是否批量处理	仅在命令行版本中	仅在命令行版本中	是
是否处理原始数据	是	是	是
是否进行质量控制和质量过滤	是	是	是
是否检测非结核分枝杆菌	否	是	是
是否能修改突变数据库	是	是	否
是否能判断菌株家系	是	是	是
检测结果是否简单易懂	是	是	是

药品名称检测工具及结果	DST结果		敏感度[%(95CI)]	特异度[%(95CI)]
药品名称检测工具及结果	耐药(株)	敏感(株)	敏感度[%(95CI)]	特异度[%(95CI)]
氟喹诺酮类
TB Profiler			81.48(74.63~87.14)	96.50(94.10~98.13)
耐药	132	13
敏感	30	359
Mykrobe			82.10(75.31~87.67)	98.12(96.16~99.24)
耐药	133	7
敏感	29	365
PhyResSE			88.27(82.29~92.79)	96.77(94.43~98.32)
耐药	143	12
敏感	19	360
阿米卡星
TB Profiler			48.89(33.70~64.23)	99.80(98.85~99.99)
耐药	22	1
敏感	23	483
Mykrobe			55.56(40.00~70.36)	99.59(98.52~99.95)
耐药	25	2
敏感	20	482
PhyResSE			60.00(44.33~74.30)	99.59(98.52~99.95)
耐药	27	2
敏感	18	482
链霉素
TB Profiler			78.77(73.92~83.09)	88.89(83.80~92.82)
耐药	256	23
敏感	69	184
Mykrobe			76.00(70.98~80.54)	89.37(84.35~93.22)
耐药	247	22
敏感	78	185
PhyResSE			79.38(74.57~83.65)	90.34(85.47~94.00)
耐药	258	20
敏感	67	187