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A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks.

ABSTRACT: Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions, though largely as a retrospective tool. Prospective monitoring, in which samples are continuously added and compared to previous samples, can generate more actionable information. To enable prospective pathogen comparison, genomic relatedness metrics based on single-nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare, i.e., the core genome, is critical to obtain a good metric. We propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436 S. aureus, 1362 K. pneumoniae and 348 E. faecium samples, ROC curves demonstrate that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high sensitivity: in a set of 2335 S. aureus samples, it correctly identifies 44 out of 44 known outbreak samples, whereas the conserved-gene method confirms 38 known outbreak samples.

SUBMITTER: Aggelen HV

PROVIDER: S-EPMC6534532 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks.

Aggelen Helen van HV Kolde Raivo R Chamarthi Hareesh H Loving Joshua J Fan Yu Y Fallon John T JT Huang Weihua W Wang Guiqing G Fortunato-Habib Mary M MM Carmona Juan J JJ Gross Brian D BD

Scientific reports 20190524 1

Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions, though largely as a retrospective tool. Prospective monitoring, in which samples are continuously added and compared to previous samples, can generate more actionable information. To enable prospective pathogen comparison, genomic relatedness metrics based on single-nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The cho ...[more]

PMID: 31127153

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Project description:BackgroundThe severity of COVID-19, as well as the speed and scale of its spread, has posed a global challenge. Countries around the world have implemented stringent non-pharmaceutical interventions (NPI) to control transmission and prevent health systems from being overwhelmed. These NPI have had profound negative social and economic impacts. With the timeline to worldwide vaccine roll-out being uncertain, governments need to consider to what extent they need to implement and how to de-escalate these NPI. This rapid review collates de-escalation criteria reported in the literature to provide a guide to criteria that could be used as part of de-escalation strategies globally.MethodsWe reviewed literature published since 2000 relating to pandemics and infectious disease outbreaks. The searches included Embase.com (includes Embase and Medline), LitCovid, grey literature searching, reference harvesting and citation tracking. Over 1,700 documents were reviewed, with 39 documents reporting de-escalation criteria included in the final analysis. Concepts retrieved through a thematic analysis of the included documents were interlinked to build a conceptual dynamic de-escalation framework.ResultsWe identified 52 de-escalation criteria, the most common of which were clustered under surveillance (cited by 43 documents, 10 criteria e.g. ability to actively monitor confirmed cases and contact tracing), health system capacity (cited by 30 documents, 11 criteria, e.g. ability to treat all patients within normal capacity) and epidemiology (cited by 28 documents, 7 criteria, e.g. number or changes in case numbers). De-escalation is a gradual and bi-directional process, and resurgence of infections or emergence of variants of concerns can lead to partial or full re-escalation(s) of response and control measures in place. Hence, it is crucial to rely on a robust public health surveillance system.ConclusionsThis rapid review focusing on de-escalation within the context of COVID-19 provides a conceptual framework and a guide to criteria that countries can use to formulate de-escalation plans.

Dataset Information

A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks.

Publications

A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks.

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