title: On the Identifiability of Transmission Dynamic Models for Infectious Diseases.
abstract: Understanding the transmission dynamics of infectious diseases is important for both biological research and public health applications. It has been widely demonstrated that statistical modeling provides a firm basis for inferring relevant epidemiological quantities from incidence and molecular data. However, the complexity of transmission dynamic models presents two challenges: (1) the likelihood function of the models is generally not computable, and computationally intensive simulation-based inference methods need to be employed, and (2) the model may not be fully identifiable from the available data. While the first difficulty can be tackled by computational and algorithmic advances, the second obstacle is more fundamental. Identifiability issues may lead to inferences that are driven more by prior assumptions than by the data themselves. We consider a popular and relatively simple yet analytically intractable model for the spread of tuberculosis based on classical IS6110 fingerprinting data. We report on the identifiability of the model, also presenting some methodological advances regarding the inference. Using likelihood approximations, we show that the reproductive value cannot be identified from the data available and that the posterior distributions obtained in previous work have likely been substantially dominated by the assumed prior distribution. Further, we show that the inferences are influenced by the assumed infectious population size, which generally has been kept fixed in previous work. We demonstrate that the infectious population size can be inferred if the remaining epidemiological parameters are already known with sufficient precision.
authors.affiliation: Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland jarno.lintusaari@aalto.fi.
authors.forename: Jarno
authors.initials: J
authors.lastname: Lintusaari
authors.affiliation: Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland Helsinki Institute for Information Technology (HIIT) and Department of Mathematics and Statistics, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Michael U
authors.initials: MU
authors.lastname: Gutmann
authors.affiliation: Helsinki Institute for Information Technology (HIIT) and Department of Computer Science, Aalto University, FI-00076 Aalto, Finland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kaski
authors.affiliation: Helsinki Institute for Information Technology (HIIT) and Department of Mathematics and Statistics, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
mesh_terms: D000465:Algorithms; D000483:Alleles; D001499:Bayes Theorem; D003141:Communicable Diseases / Q000635:transmission*; D003198:Computer Simulation; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D059645:Mutation Rate; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D011156:Population Density; D014376:Tuberculosis / Q000635:transmission
keywords: approximate Bayesian computation; identifiability; intractable likelihood; transmission dynamic models; tuberculosis