A robust Bayesian two-sample test for detecting intervals of differential gene expression in microarray time series.

Understanding the regulatory mechanisms that are responsible for an organism's response to environmental change is an important issue in molecular biology. A first and important step towards this goal is to detect genes whose expression levels are affected by altered external conditions. A range of methods to test for differential gene expression, both in static as well as in time-course experiments, have been proposed. While these tests answer the question whether a gene is differentially expressed, they do not explicitly address the question when a gene is differentially expressed, although this information may provide insights into the course and causal structure of regulatory programs. In this article, we propose a two-sample test for identifying intervals of differential gene expression in microarray time series. Our approach is based on Gaussian process regression, can deal with arbitrary numbers of replicates, and is robust with respect to outliers. We apply our algorithm to study the response of Arabidopsis thaliana genes to an infection by a fungal pathogen using a microarray time series dataset covering 30,336 gene probes at 24 observed time points. In classification experiments, our test compares favorably with existing methods and provides additional insights into time-dependent differential expression.

Model structure and uncertainty for stochastic non-point source modelling applications

The uncertainty associated with a rainfall-runoff and non-point source loading (NPS) model can be attributed to both the parameterization and model structure. An interesting implication of the areal nature of NPS models is the direct relationship between model structure (i.e. sub-watershed size) and sample size for the parameterization of spatial data. The approach of this research is to find structural limitations in scale for the use of the conceptual NPS model, then examine the scales at which suitable stochastic depictions of key parameter sets can be generated. The overlapping regions are optimal (and possibly the only suitable regions) for conducting meaningful stochastic analysis with a given NPS model. Previous work has sought to find optimal scales for deterministic analysis (where, in fact, calibration can be adjusted to compensate for sub-optimal scale selection); however, analysis of stochastic suitability and uncertainty associated with both the conceptual model and the parameter set, as presented here, is novel; as is the strategy of delineating a watershed based on the uncertainty distribution. The results of this paper demonstrate a narrow range of acceptable model structure for stochastic analysis in the chosen NPS model. In the case examined, the uncertainties associated with parameterization and parameter sensitivity are shown to be outweighed in significance by those resulting from structural and conceptual decisions. © 2011 Copyright IAHS Press.