ResFinder 4.0 for predictions of phenotypes from genotypes.

ResFinder 4.0 for predictions of phenotypes from genotypes.
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DOI:
10.1093/jac/dkaa345
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发表时间:
2020-12-01
期刊:
The Journal of antimicrobial chemotherapy
影响因子:
--
通讯作者:
Aarestrup FM
Aarestrup FM
中科院分区:
其他
文献类型:
--
作者:
Bortolaia V;Kaas RS;Ruppe E;Roberts MC;Schwarz S;Cattoir V;Philippon A;Allesoe RL;Rebelo AR;Florensa AF;Fagelhauer L;Chakraborty T;Neumann B;Werner G;Bender JK;Stingl K;Nguyen M;Coppens J;Xavier BB;Malhotra-Kumar S;Westh H;Pinholt M;Anjum MF;Duggett NA;Kempf I;Nykäsenoja S;Olkkola S;Wieczorek K;Amaro A;Clemente L;Mossong J;Losch S;Ragimbeau C;Lund O;Aarestrup FM

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对于几种抗菌剂/细菌组合,基于WGS的抗菌药敏感性试验(AST)与表型AST一样可靠。然而,由于需要生物信息学技能和抗菌素耐药性(AMR)决定因素的知识来操作迄今为止开发的绝大多数工具,基于WGS的AST的常规使用受到阻碍。通过利用ResFinder和PointFinder这两个免费访问的工具,也可以帮助没有生物信息学技能的用户,我们的目标是提高他们的速度,并提供易于解释的抗菌图作为输出。ResFinder代码已重写,以处理原始读取并使用基于Kmer的对齐。对现有的ResFinder和PointFinder数据库进行了修订和扩展。还开发了其他数据库,包括将每个AMR决定因素与抗菌化合物水平的表型相关联的表型-表型关键字,以及硅胶抗菌图谱中的物种特定小组。用大肠杆菌(n = 5 84)、沙门氏菌验证Resfinder4.0。(n = 1081)、空肠弯曲杆菌(n = 239)、屎肠球菌(n = 106)、粪肠球菌(n = 50)和金黄色葡萄球菌(n = 163)表现出不同的天冬氨酸氨基转移酶谱,来自不同的人、动物来源和地理来源。在革兰氏阴性菌和革兰氏阳性菌评估的抗菌药/菌种组合中,46/51和25/32的基因-表型符合率分别为≥95%。当基因型-表型符合率为95%时,差异主要与表型测试的解释标准和次优序列质量有关,而与Resfinder 4.0的性能无关。使用Resfinder 4.0的基于WGS的AST在计算机抗生素图谱中提供与表型AST获得的一样可靠的结果,至少对于考虑的与主要公共卫生相关的细菌种类/抗菌剂是如此。
WGS-based antimicrobial susceptibility testing (AST) is as reliable as phenotypic AST for several antimicrobial/bacterial species combinations. However, routine use of WGS-based AST is hindered by the need for bioinformatics skills and knowledge of antimicrobial resistance (AMR) determinants to operate the vast majority of tools developed to date. By leveraging on ResFinder and PointFinder, two freely accessible tools that can also assist users without bioinformatics skills, we aimed at increasing their speed and providing an easily interpretable antibiogram as output. The ResFinder code was re-written to process raw reads and use Kmer-based alignment. The existing ResFinder and PointFinder databases were revised and expanded. Additional databases were developed including a genotype-to-phenotype key associating each AMR determinant with a phenotype at the antimicrobial compound level, and species-specific panels for in silico antibiograms. ResFinder 4.0 was validated using Escherichia coli (n = 584), Salmonella spp. (n = 1081), Campylobacter jejuni (n = 239), Enterococcus faecium (n = 106), Enterococcus faecalis (n = 50) and Staphylococcus aureus (n = 163) exhibiting different AST profiles, and from different human and animal sources and geographical origins. Genotype–phenotype concordance was ≥95% for 46/51 and 25/32 of the antimicrobial/species combinations evaluated for Gram-negative and Gram-positive bacteria, respectively. When genotype–phenotype concordance was <95%, discrepancies were mainly linked to criteria for interpretation of phenotypic tests and suboptimal sequence quality, and not to ResFinder 4.0 performance. WGS-based AST using ResFinder 4.0 provides in silico antibiograms as reliable as those obtained by phenotypic AST at least for the bacterial species/antimicrobial agents of major public health relevance considered.
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