Bayesian Optimal Design for Ordinary Differential Equation Models With Application in Biological Science

© 2019 The Author(s). Bayesian optimal design is considered for experiments where the response distribution depends on the solution to a system of nonlinear ordinary differential equations. The motivation is an experiment to estimate parameters in the equations governing the transport of amino acids through cell membranes in human placentas. Decision-theoretic Bayesian design of experiments for such nonlinear models is conceptually very attractive, allowing the formal incorporation of prior knowledge to overcome the parameter dependence of frequentist design and being less reliant on asymptotic approximations. However, the necessary approximation and maximization of the, typically analytically intractable, expected utility results in a computationally challenging problem. These issues are further exacerbated if the solution to the differential equations is not available in closed-form. This article proposes a new combination of a probabilistic solution to the equations embedded within a Monte Carlo approximation to the expected utility with cyclic descent of a smooth approximation to find the optimal design. A novel precomputation algorithm reduces the computational burden, making the search for an optimal design feasible for bigger problems. The methods are demonstrated by finding new designs for a number of common models derived from differential equations, and by providing optimal designs for the placenta experiment. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.The second author was supported by Fellowship EP/J018317/1 from the United Kingdom Engineering and Physical Sciences Research Council

Genome-wide DNA-(de)methylation is associated with Noninfectious Bud-failure exhibition in Almond (Prunus dulcis [Mill.] D.A.Webb)

Noninfectious bud-failure (BF) remains a major threat to almond production in California, particularly with the recent rapid expansion of acreage and as more intensive cultural practices and modern cultivars are adopted. BF has been shown to be inherited in both vegetative and sexual progeny, with exhibition related to the age and propagation history of scion clonal sources. These characteristics suggest an epigenetic influence, such as the loss of juvenility mediated by DNA-(de)methylation. Various degrees of BF have been reported among cultivars as well as within sources of clonal propagation of the same cultivar. Genome-wide methylation profiles for different clones within almond genotypes were developed to examine their association with BF levels and association with the chronological time from initial propagation. The degree of BF exhibition was found to be associated with DNA-(de)methylation and clonal age, which suggests that epigenetic changes associated with ageing may be involved in the differential exhibition of BF within and among almond clones. Research is needed to investigate the potential of DNA-(de)methylation status as a predictor for BF as well as for effective strategies to improve clonal selection against age related deterioration. This is the first report of an epigenetic-related disorder threatening a major tree crop

Diversity, Heterotrophy, Autotropy, and Relationships among Microorganisms in Antarctica

Campaña He52 del B.I.O Hespérides - Cruise He52 of R/V Hespérides.-- 5 pages, 2 figuresPeer reviewe