Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission
Abstract The global tuberculosis (TB) epidemic is driven by primary transmission. Pathogen genome sequencing is increasingly used in molecular epidemiology and outbreak investigations. Based on contact tracing and epidemiological links, Single Nucleotide Polymorphism (SNP) cut-offs, ranging from 3 t...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94646-2 |
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| author | Bastiaan R. Van der Roest Martin C. J. Bootsma Egil A. J. Fischer Matthias I. Gröschel Richard M. Anthony Rina de Zwaan Mirjam E. E. Kretzschmar Don Klinkenberg |
| author_facet | Bastiaan R. Van der Roest Martin C. J. Bootsma Egil A. J. Fischer Matthias I. Gröschel Richard M. Anthony Rina de Zwaan Mirjam E. E. Kretzschmar Don Klinkenberg |
| author_sort | Bastiaan R. Van der Roest |
| collection | DOAJ |
| description | Abstract The global tuberculosis (TB) epidemic is driven by primary transmission. Pathogen genome sequencing is increasingly used in molecular epidemiology and outbreak investigations. Based on contact tracing and epidemiological links, Single Nucleotide Polymorphism (SNP) cut-offs, ranging from 3 to 12 SNPs, identify probable transmission clusters or exclude direct transmission. However, contact tracing can be limited by recall bias and inconsistent methodologies across TB settings. We propose phylodynamic models, i.e. methods to infer transmission processes from pathogen genomes and associated epidemiological data, as an alternative reference to infer transmission events. We analyzed 2,008 whole-genome sequences from Dutch TB patients collected from 2015 to 2019. Genetic clusters were defined within a 20-SNP range, and the phylodynamic model phybreak was employed to infer transmission. Probable transmission SNP cut-offs were assessed by the proportion of inferred transmission events with a SNP distance below these cut-offs. A total of 79 clusters were identified, with a median size of 4 isolates (IQR = 3-8). A SNP cut-off of 4 captured 98% of inferred transmission events while reducing pairs without transmission links. A cut-off beyond 12 SNPs effectively excluded transmission. Phylodynamic approaches provide a valuable alternative to contact tracing for defining SNP cut-offs, allowing for a more precise assessment of transmission events. |
| format | Article |
| id | doaj-art-66fd726ef83e49efadec4962f9eebdfc |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-66fd726ef83e49efadec4962f9eebdfc2025-08-20T02:49:26ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-94646-2Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmissionBastiaan R. Van der Roest0Martin C. J. Bootsma1Egil A. J. Fischer2Matthias I. Gröschel3Richard M. Anthony4Rina de Zwaan5Mirjam E. E. Kretzschmar6Don Klinkenberg7Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityPopulation Health Sciences, Faculty of Veterinary Medicine, University UtrechtDepartment of Infectious Diseases, Respiratory and Critical Care Medicine, Charité- Universitätsmedizin BerlinTuberculosis Reference Laboratory, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM)Tuberculosis Reference Laboratory, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM)Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityNational Institute for Public Health and the Environment (RIVM)Abstract The global tuberculosis (TB) epidemic is driven by primary transmission. Pathogen genome sequencing is increasingly used in molecular epidemiology and outbreak investigations. Based on contact tracing and epidemiological links, Single Nucleotide Polymorphism (SNP) cut-offs, ranging from 3 to 12 SNPs, identify probable transmission clusters or exclude direct transmission. However, contact tracing can be limited by recall bias and inconsistent methodologies across TB settings. We propose phylodynamic models, i.e. methods to infer transmission processes from pathogen genomes and associated epidemiological data, as an alternative reference to infer transmission events. We analyzed 2,008 whole-genome sequences from Dutch TB patients collected from 2015 to 2019. Genetic clusters were defined within a 20-SNP range, and the phylodynamic model phybreak was employed to infer transmission. Probable transmission SNP cut-offs were assessed by the proportion of inferred transmission events with a SNP distance below these cut-offs. A total of 79 clusters were identified, with a median size of 4 isolates (IQR = 3-8). A SNP cut-off of 4 captured 98% of inferred transmission events while reducing pairs without transmission links. A cut-off beyond 12 SNPs effectively excluded transmission. Phylodynamic approaches provide a valuable alternative to contact tracing for defining SNP cut-offs, allowing for a more precise assessment of transmission events.https://doi.org/10.1038/s41598-025-94646-2Phylodynamic modelingWhole Genome SequencingSNP cut-off assessmentTuberculosisTransmission |
| spellingShingle | Bastiaan R. Van der Roest Martin C. J. Bootsma Egil A. J. Fischer Matthias I. Gröschel Richard M. Anthony Rina de Zwaan Mirjam E. E. Kretzschmar Don Klinkenberg Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission Scientific Reports Phylodynamic modeling Whole Genome Sequencing SNP cut-off assessment Tuberculosis Transmission |
| title | Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission |
| title_full | Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission |
| title_fullStr | Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission |
| title_full_unstemmed | Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission |
| title_short | Phylodynamic assessment of SNP distances from whole genome sequencing for determining Mycobacterium tuberculosis transmission |
| title_sort | phylodynamic assessment of snp distances from whole genome sequencing for determining mycobacterium tuberculosis transmission |
| topic | Phylodynamic modeling Whole Genome Sequencing SNP cut-off assessment Tuberculosis Transmission |
| url | https://doi.org/10.1038/s41598-025-94646-2 |
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