Dataset Information

Bacterial genomic epidemiology with mixed samples.

ABSTRACT: Genomic epidemiology is a tool for tracing transmission of pathogens based on whole-genome sequencing. We introduce the mGEMS pipeline for genomic epidemiology with plate sweeps representing mixed samples of a target pathogen, opening the possibility to sequence all colonies on selective plates with a single DNA extraction and sequencing step. The pipeline includes the novel mGEMS read binner for probabilistic assignments of sequencing reads, and the scalable pseudoaligner Themisto. We demonstrate the effectiveness of our approach using closely related samples in a nosocomial setting, obtaining results that are comparable to those based on single-colony picks. Our results lend firm support to more widespread consideration of genomic epidemiology with mixed infection samples.

SUBMITTER: Maklin T

PROVIDER: S-EPMC8743562 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Bacterial genomic epidemiology with mixed samples.

Mäklin Tommi T Kallonen Teemu T Alanko Jarno J Samuelsen Ørjan Ø Hegstad Kristin K Mäkinen Veli V Corander Jukka J Heinz Eva E Honkela Antti A

Microbial genomics 20211101 11

Genomic epidemiology is a tool for tracing transmission of pathogens based on whole-genome sequencing. We introduce the mGEMS pipeline for genomic epidemiology with plate sweeps representing mixed samples of a target pathogen, opening the possibility to sequence all colonies on selective plates with a single DNA extraction and sequencing step. The pipeline includes the novel mGEMS read binner for probabilistic assignments of sequencing reads, and the scalable pseudoaligner Themisto. We demonstra ...[more]

PMID: 34779765

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Project description:BackgroundEpidemiological surveillance relies on microbial strain typing, which defines genomic relatedness among isolates to identify case clusters and their potential sources. Although predefined thresholds are often applied, known outbreak-specific features such as pathogen mutation rate and duration of source contamination are rarely considered. We aimed to develop a hypothesis-based model that estimates genetic distance thresholds and mutation rates for point-source single-strain food or environmental outbreaks.MethodsIn this modelling study, we developed a forward model to simulate bacterial evolution at a specific mutation rate (μ) over a defined outbreak duration (D). From the distribution of genetic distances expected under the given outbreak parameters and sample isolation dates, we estimated a distance threshold beyond which isolates should not be considered as part of the outbreak. We embedded the model into a Markov Chain Monte Carlo inference framework to estimate the most probable mutation rate or time since source contamination, which are both often imprecisely documented. A simulation study validated the model over realistic durations and mutation rates. We then identified and analysed 16 published datasets of bacterial source-related outbreaks; datasets were included if they were from an identified foodborne outbreak and if whole-genome sequence data and collection dates for the described isolates were available.FindingsAnalysis of simulated data validated the accuracy of our framework in both discriminating between outbreak and non-outbreak cases and estimating the parameters D and μ from outbreak data. Precision of estimation was much higher for high values of D and μ. Sensitivity of outbreak cases was always very high, and specificity in detecting non-outbreak cases was poor for low mutation rates. For 14 of the 16 outbreaks, the classification of isolates as being outbreak-related or sporadic is consistent with the original dataset. Four of these outbreaks included outliers, which were correctly classified as being beyond the threshold of exclusion estimated by our model, except for one isolate of outbreak 4. For two outbreaks, both foodborne Listeria monocytogenes, conclusions from our model were discordant with published results: in one outbreak two isolates were classified as outliers by our model and in another outbreak our algorithm separated food samples into one cluster and human samples into another, whereas the isolates were initially grouped together based on epidemiological and genetic evidence. Re-estimated values of the duration of outbreak or mutation rate were largely consistent with a priori defined values. However, in several cases the estimated values were higher and improved the fit with the observed genetic distance distribution, suggesting that early outbreak cases are sometimes missed.InterpretationWe propose here an evolutionary approach to the single-strain conundrum by estimating the genetic threshold and proposing the most probable cluster of cases for a given outbreak, as determined by its particular epidemiological and microbiological properties. This forward model, applicable to foodborne or environmental-source single point case clusters or outbreaks, is useful for epidemiological surveillance and may inform control measures.FundingEuropean Union Horizon 2020 Research and Innovation Programme.

Dataset Information

Bacterial genomic epidemiology with mixed samples.

Publications

Bacterial genomic epidemiology with mixed samples.

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