PMID- 30948181 OWN - NLM STAT- MEDLINE DCOM- 20200107 LR - 20200107 IS - 1873-281X (Electronic) IS - 1472-9792 (Linking) VI - 115 DP - 2019 Mar TI - Evaluation of a gene-by-gene approach for prospective whole-genome sequencing-based surveillance of multidrug resistant Mycobacterium tuberculosis. PG - 81-88 LID - S1472-9792(18)30474-8 [pii] LID - 10.1016/j.tube.2019.02.006 [doi] AB - Whole-genome sequencing (WGS) offers unprecedented resolution for tracking Mycobacterium tuberculosis transmission and antibiotic-resistance spread. Still, the establishment of standardized WGS-based pipelines and the definition of epidemiological clusters based on genetic relatedness are under discussion. We aimed to implement a dynamic gene-by-gene approach, fully relying on freely available software, for prospective WGS-based tuberculosis surveillance, demonstrating its application for detecting transmission chains by retrospectively analysing all M/XDR strains isolated in 2013-2017 in Portugal. We observed a good correlation between genetic relatedness and epidemiological links, with strongly epilinked clusters displaying mean pairwise allele differences (AD) always below 0.3% (ratio of mean AD over the total number of shared loci between same-cluster strains). This data parallels the genetic distances acquired by the core-SNV analysis, while providing higher resolution and epidemiological concordance than MIRU-VNTR genotyping. The dynamic analysis of strain sub-sets (i.e., increasing the number of shared loci within each sub-set) also strengthens the confidence in detecting epilinked clusters. This gene-by-gene strategy also offers several practical benefits (e.g., reliance on freely-available software, scalability and low computational requirements) that further consolidated its suitability for a timely and robust prospective WGS-based laboratory surveillance of M/XDR-TB cases. CI - Copyright (c) 2019. Published by Elsevier Ltd. FAU - Macedo, Rita AU - Macedo R AD - National Reference Laboratory for Mycobacteria, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: rita.macedo@insa.min-saude.pt. FAU - Pinto, Miguel AU - Pinto M AD - Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: miguel.pinto@insa.min-saude.pt. FAU - Borges, Vitor AU - Borges V AD - Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: vitor.borges@insa.min-saude.pt. FAU - Nunes, Alexandra AU - Nunes A AD - Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: alexandra.nunes@insa.min-saude.pt. FAU - Oliveira, Olena AU - Oliveira O AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; ICVS/3B, PT Government Associate Laboratory, 4710-057, Braga/4805-017, Guimaraes, Portugal; EPI Unit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal. Electronic address: radomoliveira@gmail.com. FAU - Portugal, Isabel AU - Portugal I AD - iMed.ULisboa-Research Institute for Medicines, University of Lisbon, Lisbon, Portugal. Electronic address: iportugal@ff.ulisboa.pt. FAU - Duarte, Raquel AU - Duarte R AD - EPI Unit, Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; Clinical Epidemiology, Predictive Medicine and Public Health Department, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; Pulmonology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho EPE, 4400-129 Vila Nova de Gaia, Portugal. Electronic address: raquelafduarte@gmail.com. FAU - Gomes, Joao Paulo AU - Gomes JP AD - Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health, 1649-016 Lisbon, Portugal. Electronic address: j.paulo.gomes@insa.min-saude.pt. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190225 PL - Scotland TA - Tuberculosis (Edinb) JT - Tuberculosis (Edinburgh, Scotland) JID - 100971555 SB - IM MH - Genes, Bacterial/*genetics MH - Genome, Bacterial MH - Genotype MH - Humans MH - Mycobacterium tuberculosis/*genetics MH - Phylogeny MH - Polymorphism, Single Nucleotide/genetics MH - Portugal/epidemiology MH - Prospective Studies MH - Tuberculosis, Multidrug-Resistant/epidemiology/*genetics MH - *Whole Genome Sequencing OTO - NOTNLM OT - Gene-by-gene approach OT - Multidrug-resistance OT - Mycobacterium tuberculosis OT - Surveillance OT - Whole-genome sequencing EDAT- 2019/04/06 06:00 MHDA- 2020/01/08 06:00 CRDT- 2019/04/06 06:00 PHST- 2018/11/08 00:00 [received] PHST- 2019/01/15 00:00 [revised] PHST- 2019/02/22 00:00 [accepted] PHST- 2019/04/06 06:00 [entrez] PHST- 2019/04/06 06:00 [pubmed] PHST- 2020/01/08 06:00 [medline] AID - S1472-9792(18)30474-8 [pii] AID - 10.1016/j.tube.2019.02.006 [doi] PST - ppublish SO - Tuberculosis (Edinb). 2019 Mar;115:81-88. doi: 10.1016/j.tube.2019.02.006. Epub 2019 Feb 25.