Doss, Charles R.; Suchard, Marc A.; Holmes, Ian; Kato-Maeda, Midori; Minin, Vladimir N. Fitting birth-death processes to panel data with applications to bacterial DNA fingerprinting. (English) Zbl 1283.92027 Ann. Appl. Stat. 7, No. 4, 2315-2335 (2013). Summary: Continuous-time linear birth-death-immigration (BDI) processes are frequently used in ecology and epidemiology to model the stochastic dynamics of the population of interest. In clinical settings, multiple birth-death processes can describe disease trajectories of individual patients, allowing for estimation of the effects of individual covariates on the birth and death rates of the process. Such estimation is usually accomplished by analyzing patient data collected at unevenly spaced time points, referred to as panel data in the biostatistics literature. Fitting linear BDI processes to panel data is a nontrivial optimization problem because birth and death rates can be functions of many parameters related to the covariates of interest. We propose a novel expectation-maximization (EM) algorithm for fitting linear BDI models with covariates to panel data. We derive a closed-form expression for the joint generating function of some of the BDI process statistics and use this generating function to reduce the E-step of the EM algorithm, as well as calculation of the Fisher information, to one-dimensional integration. This analytical technique yields a computationally efficient and robust optimization algorithm that we implemented in an open-source R package. We apply our method to DNA fingerprinting of Mycobacterium tuberculosis, the causative agent of tuberculosis, to study intrapatient time evolution of IS6110 copy number, a genetic marker frequently used during estimation of epidemiological clusters of Mycobacterium tuberculosis infections. Our analysis reveals previously undocumented differences in IS6110 birth-death rates among three major lineages of Mycobacterium tuberculosis, which has important implications for epidemiologists that use IS6110 for DNA fingerprinting of Mycobacterium tuberculosis. Cited in 7 Documents MSC: 92C40 Biochemistry, molecular biology 92C60 Medical epidemiology 60J85 Applications of branching processes 92-04 Software, source code, etc. for problems pertaining to biology 92-08 Computational methods for problems pertaining to biology 62P10 Applications of statistics to biology and medical sciences; meta analysis Keywords:missing data; EM algorithm; transposable elements; IS6110; tuberculosis Software:R; msm PDF BibTeX XML Cite \textit{C. R. Doss} et al., Ann. Appl. Stat. 7, No. 4, 2315--2335 (2013; Zbl 1283.92027) Full Text: DOI arXiv Euclid OpenURL References: [1] Alonso, H., Aguilo, J. I., Samper, S., Caminero, J. A., Campos-Herrero, M. I., Gicquel, B., Brosch, R., Martín, C. and Otal, I. (2011). Deciphering the role of IS6110 in a highly transmissible Mycobacterium tuberculosis Beijing strain, GC1237. Tuberculosis 91 117-126. [2] Baum, L. E., Petrie, T., Soules, G. and Weiss, N. (1970). 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