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Forecasting cell fate during antibiotic exposure using stochastic gene expression.

ABSTRACT: Antibiotic killing does not occur at a single, precise time for all cells within a population. Variability in time to death can be caused by stochastic expression of genes, resulting in differences in endogenous stress-resistance levels between individual cells in a population. Here we investigate whether single-cell differences in gene expression prior to antibiotic exposure are related to cell survival times after antibiotic exposure for a range of genes of diverse function. We quantified the time to death of single cells under antibiotic exposure in combination with expression of reporters. For some reporters, including genes involved in stress response and cellular processes like metabolism, the time to cell death had a strong relationship with the initial expression level of the genes. Our results highlight the single-cell level non-uniformity of antibiotic killing and also provide examples of key genes where cell-to-cell variation in expression is strongly linked to extended durations of antibiotic survival.

SUBMITTER: Rossi NA

PROVIDER: S-EPMC6624276 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Forecasting cell fate during antibiotic exposure using stochastic gene expression.

Rossi Nicholas A NA El Meouche Imane I Dunlop Mary J MJ

Communications biology 20190711

Antibiotic killing does not occur at a single, precise time for all cells within a population. Variability in time to death can be caused by stochastic expression of genes, resulting in differences in endogenous stress-resistance levels between individual cells in a population. Here we investigate whether single-cell differences in gene expression prior to antibiotic exposure are related to cell survival times after antibiotic exposure for a range of genes of diverse function. We quantified the ...[more]

PMID: 31312728

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Project description:BackgroundMonkeypox virus is gaining attention due to its severity and spread among people. This study sheds light on the modeling and forecasting of new monkeypox cases. Knowledge about the future situation of the virus using a more accurate time series and stochastic models is required for future actions and plans to cope with the challenge.MethodsWe conduct a side-by-side comparison of the machine learning approach with the traditional time series model. The multilayer perceptron model (MLP), a machine learning technique, and the Box-Jenkins methodology, also known as the ARIMA model, are used for classical modeling. Both methods are applied to the Monkeypox cumulative data set and compared using different model selection criteria such as root mean square error, mean square error, mean absolute error, and mean absolute percentage error.ResultsWith a root mean square error of 150.78, the monkeypox series follows the ARIMA (7,1,7) model among the other potential models. Comparatively, we use the multilayer perceptron (MLP) model, which employs the sigmoid activation function and has a different number of hidden neurons in a single hidden layer. The root mean square error of the MLP model, which uses a single input and ten hidden neurons, is 54.40, significantly lower than that of the ARIMA model. The actual confirmed cases versus estimated or fitted plots also demonstrate that the multilayer perceptron model has a better fit for the monkeypox data than the ARIMA model.Conclusions and recommendationWhen it comes to predicting monkeypox, the machine learning method outperforms the traditional time series. A better match can be achieved in future studies by applying the extreme learning machine model (ELM), support vector machine (SVM), and some other methods with various activation functions. It is thus concluded that the selected data provide a real picture of the virus. If the situations remain the same, governments and other stockholders should ensure the follow-up of Standard Operating Procedures (SOPs) among the masses, as the trends will continue rising in the upcoming 10 days. However, governments should take some serious interventions to cope with the virus.LimitationIn the ARIMA models selected for forecasting, we did not incorporate the effect of covariates such as the effect of net migration of monkeypox virus patients, government interventions, etc.

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Forecasting cell fate during antibiotic exposure using stochastic gene expression.

Publications

Forecasting cell fate during antibiotic exposure using stochastic gene expression.

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