DNA Microarray Time Series Analysis: Automated Statistical Assessment of Circadian Rhythms in Gene Expression Patterning

Publisher Summary This chapter describes the use of DNA microarrays in elucidation of network dynamics of circadian gene regulation. Application of this technology to circadian biology is particularly apropos given the molecular basis of intracellular circadian regulation, a system of transcriptional–translational feedback control. The COSOPT algorithm evolved as an extension of the CORRCOS algorithm and has been applied to search for diurnal/circadian gene expression profiling in mammalian and Drosophila microarray time series. Simulated data sets were prepared to approximate gene chip profiles from the experimental examinations of expression time series. The straightforward, direct approximation by nonlinear least squares optimization of a single-frequency cosine function to the data in question produced admirable performance under conditions in which pointwise uncertainties are not considered, but produced the highest false-positive rate of all the methods when pointwise uncertainties were considered. It is found that COSOPT also reports information about mean expression level and can use this information as an exclusionary criterion.

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