A Function-Centric Approach to the Biological Interpretation of Microarray Time-Series

Pablo Minguez[1] (pminguez@cipf.es)
Fátima Al-Shahrour[1] (falshahrour@cipf.es)
Joaquín Dopazo[1],[2] (jdopazo@cipf.es)

[1]Bioinformatics Department, Centro de Investigación Príncipe Felipe (CIPF), Autopista del Saler 16, E46013, Valencia, Spain
[2]Functional Genomics Node, INB-CIPF, Autopista del Saler 16, E-46013, Valencia, Spain

Abstract

The interpretation of microarray experiments is commonly addressed by means a two-step approach in which the relevant genes are firstly selected uniquely on the basis of their experimental values (ignoring their coordinate behaviors) and in a second step their functional properties are studied to hypothesize about the biological roles they are fulfilling in the cell. Recently, different methods (e.g. GSEA or FatiScan) have been proposed to study the coordinate behavior of blocks of functionally-related genes. These methods study the distribution of functional information across lists of genes ranked according their different experimental values in a static situation, such as the comparison between two classes (e.g. healthy controls versus diseased cases). Nevertheless there is no an equivalent way of studying a dynamic situation from a functional point of view.
We present a method for the functional analysis of microarrays series in which the experiments display autocorrelation between successive points (e.g. time series, dose-response experiments, etc.) The method allows to recover the dynamics of the molecular roles fulfilled by the genes along the series which provides a novel approach to functional interpretation of such experiments. The method finds blocks of functionally-related genes which are significantly and coordinately over-expressed at different points of the series. This method draws inspiration from systems biology given that the analysis does not focus on individual properties of genes but on collective behaving blocks of functionally-related genes.
The FatiScan algorithm used in the method proposed is available at: http://fatiscan.bioinfo.cipf.es, or within the Babelomics suite: http://www.babelomics.org. Additional material is available at: http://bioinfo.cipf.es/data/plasmodium

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