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Bioinformatics. 2002 Nov;18(11):1477-85.

Statistical analysis of a small set of time-ordered gene expression data using linear splines.

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Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.



Recently, the temporal response of genes to changes in their environment has been investigated using cDNA microarray technology by measuring the gene expression levels at a small number of time points. Conventional techniques for time series analysis are not suitable for such a short series of time-ordered data. The analysis of gene expression data has therefore usually been limited to a fold-change analysis, instead of a systematic statistical approach.


We use the maximum likelihood method together with Akaike's Information Criterion to fit linear splines to a small set of time-ordered gene expression data in order to infer statistically meaningful information from the measurements. The significance of measured gene expression data is assessed using Student's t-test.


Previous gene expression measurements of the cyanobacterium Synechocystis sp. PCC6803 were reanalyzed using linear splines. The temporal response was identified of many genes that had been missed by a fold-change analysis. Based on our statistical analysis, we found that about four gene expression measurements or more are needed at each time point.

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