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Timothy M. D. Ebbels

Publications and source records attributed to Timothy M. D. Ebbels.

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Integrative analysis of time course metabolic data and biomarker discovery

Metabonomics time-course experiments provide the opportunity to understand the changes to an organism by observing the evolution of metabolic profiles in response to internal or external stimuli. Along with other omic longitudinal profiling technologies, these techniques have great potential to complement the analysis of complex relations between variations across diverse omic variables and provide unique insights into the underlying biology of the system. However, many statistical methods currently used to analyse short time-series omic data are i) prone to overfitting or ii) do not take into account the experimental design or iii) do not make full use of the multivariate information intrinsic to the data or iv) unable to uncover multiple associations between different omic data. The model we propose is an attempt to i) overcome overfitting by using a weakly informative Bayesian model, ii) capture experimental design conditions through a mixed-effects model, iii) model interdependencies between variables by augmenting the mixed-effects model with a conditional auto-regressive (CAR) component and iv) identify potential associations between heterogeneous omic variables .

stat.AP

Bayesian inference for multiple Gaussian graphical models with application to metabolic association networks

We investigate the effect of cadmium (a toxic environmental pollutant) on the correlation structure of a number of urinary metabolites using Gaussian graphical models (GGMs). The inferred metabolic associations can provide important information on the physiological state of a metabolic system and insights on complex metabolic relationships. Using the fitted GGMs, we construct differential networks, which highlight significant changes in metabolite interactions under different experimental conditions. The analysis of such metabolic association networks can reveal differences in the underlying biological reactions caused by cadmium exposure. We consider Bayesian inference and propose using the multiplicative (or Chung-Lu random graph) model as a prior on the graphical space. In the multiplicative model, each edge is chosen independently with probability equal to the product of the connectivities of the end nodes. This class of prior is parsimonious yet highly flexible; it can be used to encourage sparsity or graphs with a pre-specified degree distribution when such prior knowledge is available. We extend the multiplicative model to multiple GGMs linking the probability of edge inclusion through logistic regression and demonstrate how this leads to joint inference for multiple GGMs. A sequential Monte Carlo (SMC) algorithm is developed for estimating the posterior distribution of the graphs.

stat.ME