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Computational Modeling, Parameterization, and Evaluation of the Spread of Diseases
Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computational Science.
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Computer simulations play a vital role in the modeling of infectious diseases. Different modeling regimes fit specific purposes, from ordinary differential equations to probabilistic formulations. Throughout the COVID-19 pandemic, we have seen how the results from these computational models can come to dictate our daily lives and the importance of reliable results. This thesis aims to address the challenge of exploiting the increase in available computational power to build accurate models with well-understood uncertainties. The latter is essential when basing decisions on any model predictions.

Data collection relevant to epidemiology is expanding, and methods to incorporate models in data fitting need to follow suit. This thesis applies the Bayesian framework connecting data with models in a probabilistic setting. We propose simulation-based inference methods that allow for the use of complex models otherwise excluded due to their intractable likelihoods. Our computational set-up exemplifies how modelers can deploy Bayesian inference in large-scale, real-world data environments.

The thesis includes four papers relevant for modelers considering dynamic systems, approximate Bayesian inference, or epidemics. Paper I finds the approximate posterior of a complex chemical reaction network and estimates the prior and posterior uncertainties using the pathwise Fisher information matrix, thus framing our methodology in a fully synthetic setting. Paper II constructs a disease spread model for the spread of a verotoxigenic E. coli prevalent in the Swedish cattle population. The data includes a high-resolution transport network and actual bacterial-swab observations from selected farms. The results show that even if the data is sparse in space and time, it is still possible to recover a posterior that replicates the data and is viable for mitigation evaluations. Paper III studies a form of meta-models, the Ornstein-Uhlenbeck process, and how they approximate epidemiological models and enable broad analysis. We state an analytical limit of what is possible to learn from data subject to binary filters with confirming numerical examples. Finally, Paper IV finds a posterior model of the COVID-19 pandemic in Sweden and the 21 regions using a Kalman filter approximation. The findings result in a probabilistic regional surveillance tool for an epidemic at a national scale with considerable cost-cutting potential independent of large-scale testing of individuals.

In conclusion, the thesis examines how reasonably realistic and computationally expensive epidemic models can be adapted to data using a Bayesian framework without compromising model complexity and estimating uncertainties that further support decision-making.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2022. , p. 50
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2157
Keywords [en]
Parameter estimation, Bayesian modeling, Stochastic epidemiological models, simulation-based inference, approximate bayesian computations
National Category
Computational Mathematics Probability Theory and Statistics
Research subject
Scientific Computing
Identifiers
URN: urn:nbn:se:uu:diva-473445ISBN: 978-91-513-1521-8 (print)OAI: oai:DiVA.org:uu-473445DiVA, id: diva2:1654329
Public defence
2022-08-19, Heinz-Otto Kreiss, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 10:15 (English)
Opponent
Supervisors
Projects
eSSENCEAvailable from: 2022-05-24 Created: 2022-04-27 Last updated: 2022-06-15
List of papers
1. Towards Confident Bayesian Parameter Estimation in Stochastic Chemical Kinetics
Open this publication in new window or tab >>Towards Confident Bayesian Parameter Estimation in Stochastic Chemical Kinetics
2021 (English)In: Numerical Mathematics and Advanced Applications ENUMATH 2019: European Conference, Egmond aan Zee, The Netherlands, September 30 - October 4 / [ed] Fred J. Vermolen & Cornelis Vuik, Springer International Publishing Springer Nature, 2021, p. 373-380Conference paper, Published paper (Refereed)
Abstract [en]

We investigate the feasibility of Bayesian parameter inference for chemical reaction networks described in the low copy number regime. Here stochastic models are often favorable implying that the Bayesian approach becomes natural. Our discussion circles around a concrete oscillating system describing a circadian rhythm, and we ask if its parameters can be inferred from observational data. The main challenge is the lack of analytic likelihood and we circumvent this through the use of a synthetic likelihood based on summarizing statistics. We are particularly interested in the robustness and confidence of the inference procedure and therefore estimates a priori as well as a posteriori the information content available in the data. Our all-synthetic experiments are successful but also point out several challenges when it comes to real data sets.

Place, publisher, year, edition, pages
Springer NatureSpringer International Publishing, 2021
Series
Lecture Notes in Computational Science and Engineering (LNCSE), ISSN 1439-7358, E-ISSN 2197-7100 ; 139
National Category
Computational Mathematics
Identifiers
urn:nbn:se:uu:diva-463045 (URN)10.1007/978-3-030-55874-1_36 (DOI)978-3-030-55873-4 (ISBN)978-3-030-55874-1 (ISBN)
Conference
Numerical Mathematics and Advanced Applications ENUMATH 2019 European Conference, Egmond aan Zee, The Netherlands, September 30 - October 4
Projects
eSSENCE
Funder
eSSENCE - An eScience Collaboration
Available from: 2022-01-05 Created: 2022-01-05 Last updated: 2024-01-15Bibliographically approved
2. Bayesian epidemiological modeling over high-resolution network data
Open this publication in new window or tab >>Bayesian epidemiological modeling over high-resolution network data
2020 (English)In: Epidemics, ISSN 1755-4365, E-ISSN 1878-0067, Vol. 32, article id 100399Article in journal (Refereed) Published
Abstract [en]

Mathematical epidemiological models have a broad use, including both qualitative and quantitative applications. With the increasing availability of data, large-scale quantitative disease spread models can nowadays be formulated. Such models have a great potential, e.g., in risk assessments in public health. Their main challenge is model parameterization given surveillance data, a problem which often limits their practical usage. We offer a solution to this problem by developing a Bayesian methodology suitable to epidemiological models driven by network data. The greatest difficulty in obtaining a concentrated parameter posterior is the quality of surveillance data; disease measurements are often scarce and carry little information about the parameters. The often overlooked problem of the model's identifiability therefore needs to be addressed, and we do so using a hierarchy of increasingly realistic known truth experiments. Our proposed Bayesian approach performs convincingly across all our synthetic tests. From pathogen measurements of shiga toxin-producing Escherichia coli O157 in Swedish cattle, we are able to produce an accurate statistical model of first-principles confronted with data. Within this model we explore the potential of a Bayesian public health framework by assessing the efficiency of disease detection and -intervention scenarios.

Place, publisher, year, edition, pages
Elsevier BV, 2020
Keywords
Bayesian parameter estimation, Pathogen detection, Disease intervention, Synthetic likelihood, Spatial stochastic models
National Category
Computational Mathematics Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:uu:diva-421463 (URN)10.1016/j.epidem.2020.100399 (DOI)000580633700005 ()32799071 (PubMedID)
Projects
eSSENCE
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research CouncileSSENCE - An eScience CollaborationSwedish National Infrastructure for Computing (SNIC)
Available from: 2020-10-08 Created: 2020-10-08 Last updated: 2022-04-27Bibliographically approved
3. Bayesian inference in epidemics: linear noise analysis
Open this publication in new window or tab >>Bayesian inference in epidemics: linear noise analysis
2023 (English)In: Mathematical Biosciences and Engineering, ISSN 1547-1063, E-ISSN 1551-0018, Vol. 20, no 2, p. 4128-4152Article in journal (Refereed) Published
Abstract [en]

This paper offers a qualitative insight into the convergence of bayesian parameter inference in a setup which mimics the modeling of the spread of a disease with associated disease measurements. Specifically, we are interested in the Bayesian model’s convergence with increasing amounts of data under measurement limitations. Depending on how weakly informative the disease measurements are, we offer a kind of ‘best case’ as well as a ‘worst case’ analysis where, in the former case, we assume that the prevalence is directly accessible, while in the latter that only a binary signal corresponding toa prevalence detection threshold is available. Both cases are studied under an assumed so-called linear noise approximation as to the true dynamics. Numerical experiments test the sharpness of our results when confronted with more realistic situations for which analytical results are unavailable.

Place, publisher, year, edition, pages
American Institute of Mathematical Sciences, 2023
Keywords
Parameter estimation, Bayesian modeling, Stochastic epidemiological models, Network model, Ornstein-Uhlenbeck process
National Category
Computational Mathematics
Research subject
Mathematics with specialization in Applied Mathematics
Identifiers
urn:nbn:se:uu:diva-473443 (URN)10.3934/mbe.2023193 (DOI)000944657100106 ()
Projects
eSSENCE
Funder
Swedish Research Council FormasVinnova
Available from: 2022-04-27 Created: 2022-04-27 Last updated: 2023-04-13Bibliographically approved
4. Bayesian Monitoring of COVID-19 in Sweden
Open this publication in new window or tab >>Bayesian Monitoring of COVID-19 in Sweden
2023 (English)In: Epidemics, ISSN 1755-4365, E-ISSN 1878-0067, Vol. 45, article id 100715Article in journal (Refereed) Published
Abstract [en]

In an effort to provide regional decision support for the public healthcare, we design a data-driven compartment-based model of COVID-19 in Sweden. From national hospital statistics we derive parameter priors, and we develop linear filtering techniques to drive the simulations given data in the form of daily healthcare demands. We additionally propose a posterior marginal estimator which provides for an improved temporal resolution of the reproduction number estimate as well as supports robustness checks via a parametric bootstrap procedure.

From our computational approach we obtain a Bayesian model of predictive value which provides important insight into the progression of the disease, including estimates of the effective reproduction number, the infection fatality rate, and the regional-level immunity. We successfully validate our posterior model against several different sources, including outputs from extensive screening programs. Since our required data in comparison is easy and non-sensitive to collect, we argue that our approach is particularly promising as a tool to support monitoring and decisions within public health.

Significance: Using public data from Swedish patient registries we develop a national-scale computational model of COVID-19. The parametrized model produces valuable weekly predictions of healthcare demands at the regional level and validates well against several different sources. We also obtain critical epidemiological insights into the disease progression, including, e.g., reproduction number, immunity and disease fatality estimates. The success of the model hinges on our novel use of filtering techniques which allows us to design an accurate data-driven procedure using data exclusively from healthcare demands, i.e., our approach does not rely on public testing and is therefore very cost-effective.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Bayesian forecasting, Public health situation awareness, Data-driven epidemics, Compartment-based model, Kalman filtering
National Category
Computational Mathematics Public Health, Global Health and Social Medicine
Research subject
Scientific Computing
Identifiers
urn:nbn:se:uu:diva-473444 (URN)10.1016/j.epidem.2023.100715 (DOI)001077959200001 ()
Projects
eSSENCE - An eScience Collaboration
Funder
VinnovaSwedish Research Council FormasSwedish Research Council
Available from: 2022-04-27 Created: 2022-04-27 Last updated: 2026-01-08Bibliographically approved

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