OutbreakFlow: Model-based Bayesian inference of disease outbreak dynamics with invertible neural networks and its application to the COVID-19 pandemics in Germany
Mathematical models in epidemiology are an indispensable tool to determine the dynamics and important characteristics of infectious diseases. Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However,...
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description | Mathematical models in epidemiology are an indispensable tool to determine the dynamics and important characteristics of infectious diseases. Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However, reliably inferring the epidemical dynamics by connecting complex models to real data is still hard and requires either laborious manual parameter fitting or expensive optimization methods which have to be repeated from scratch for every application of a given model. In this work, we address this problem with a novel combination of epidemiological modeling with specialized neural networks. Our approach entails two computational phases: In an initial training phase, a mathematical model describing the epidemic is used as a coach for a neural network, which acquires global knowledge about the full range of possible disease dynamics. In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. Application of our method to the early Covid-19 outbreak phase in Germany demonstrates that we are able to obtain reliable probabilistic estimates for important disease characteristics, such as generation time, fraction of undetected infections, likelihood of transmission before symptom onset, and reporting delays using a very moderate amount of real-world observations. |
doi_str_mv | 10.1371/journal.pcbi.1009472 |
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Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However, reliably inferring the epidemical dynamics by connecting complex models to real data is still hard and requires either laborious manual parameter fitting or expensive optimization methods which have to be repeated from scratch for every application of a given model. In this work, we address this problem with a novel combination of epidemiological modeling with specialized neural networks. Our approach entails two computational phases: In an initial training phase, a mathematical model describing the epidemic is used as a coach for a neural network, which acquires global knowledge about the full range of possible disease dynamics. In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. Application of our method to the early Covid-19 outbreak phase in Germany demonstrates that we are able to obtain reliable probabilistic estimates for important disease characteristics, such as generation time, fraction of undetected infections, likelihood of transmission before symptom onset, and reporting delays using a very moderate amount of real-world observations.</description><identifier>ISSN: 1553-7358</identifier><identifier>ISSN: 1553-734X</identifier><identifier>EISSN: 1553-7358</identifier><identifier>DOI: 10.1371/journal.pcbi.1009472</identifier><identifier>PMID: 34695111</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Bayes Theorem ; Bayesian analysis ; Bayesian statistical decision theory ; Biology and Life Sciences ; Calibration ; Computer and Information Sciences ; Computer applications ; Control ; Coronaviruses ; COVID-19 ; COVID-19 - epidemiology ; Disease transmission ; Dynamics ; Epidemic models ; Epidemics ; Epidemiology ; Estimates ; Germany - epidemiology ; Humans ; Infectious diseases ; Knowledge acquisition ; Mathematical models ; Medicine and Health Sciences ; Methods ; Models, Biological ; Neural networks ; Neural Networks, Computer ; Optimization ; Ordinary differential equations ; Outbreaks ; Pandemics ; Parameter estimation ; Parameters ; People and places ; Public health ; Research and Analysis Methods ; Simulation ; Statistical inference ; Time series ; Uncertainty</subject><ispartof>PLoS computational biology, 2021-10, Vol.17 (10), p.e1009472-e1009472</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Radev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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epidemiology</topic><topic>Disease transmission</topic><topic>Dynamics</topic><topic>Epidemic models</topic><topic>Epidemics</topic><topic>Epidemiology</topic><topic>Estimates</topic><topic>Germany - epidemiology</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Knowledge acquisition</topic><topic>Mathematical models</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Models, Biological</topic><topic>Neural networks</topic><topic>Neural Networks, Computer</topic><topic>Optimization</topic><topic>Ordinary differential equations</topic><topic>Outbreaks</topic><topic>Pandemics</topic><topic>Parameter estimation</topic><topic>Parameters</topic><topic>People and places</topic><topic>Public health</topic><topic>Research and Analysis Methods</topic><topic>Simulation</topic><topic>Statistical inference</topic><topic>Time series</topic><topic>Uncertainty</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Radev, Stefan T</creatorcontrib><creatorcontrib>Graw, Frederik</creatorcontrib><creatorcontrib>Chen, Simiao</creatorcontrib><creatorcontrib>Mutters, Nico T</creatorcontrib><creatorcontrib>Eichel, Vanessa M</creatorcontrib><creatorcontrib>Bärnighausen, Till</creatorcontrib><creatorcontrib>Köthe, Ullrich</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Computing Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Computer Science Collection</collection><collection>Computer Science Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Computing Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. 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subjects | Bayes Theorem Bayesian analysis Bayesian statistical decision theory Biology and Life Sciences Calibration Computer and Information Sciences Computer applications Control Coronaviruses COVID-19 COVID-19 - epidemiology Disease transmission Dynamics Epidemic models Epidemics Epidemiology Estimates Germany - epidemiology Humans Infectious diseases Knowledge acquisition Mathematical models Medicine and Health Sciences Methods Models, Biological Neural networks Neural Networks, Computer Optimization Ordinary differential equations Outbreaks Pandemics Parameter estimation Parameters People and places Public health Research and Analysis Methods Simulation Statistical inference Time series Uncertainty |
title | OutbreakFlow: Model-based Bayesian inference of disease outbreak dynamics with invertible neural networks and its application to the COVID-19 pandemics in Germany |
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