Iterative Group Analysis (iGA): A simple tool to enhance sensitivity and facilitate interpretation of microarray experiments

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Abstract
The biological interpretation of even a simple microarray experiment can be a challenging and highly complex task. Here we present a new method (Iterative Group Analysis) to facilitate, improve, and accelerate this process. Our Iterative Group Analysis approach (iGA) uses elementary statistics to identify those functional classes of genes that are significantly changed in an experiment and at the same time determines which of the class members are most likely to be differentially expressed. iGA does not require that all members of a class change and is therefore robust against imperfect class assignments, which can be derived from public sources (e.g. GeneOntologies) or automated processes (e.g. key word extraction from gene names). In contrast to previous non-iterative approaches, iGA does not depend on the availability of fixed lists of differentially expressed genes, and thus can be used to increase the sensitivity of gene detection especially in very noisy or small data sets. In the extreme, iGA can even produce statistically meaningful results without any experimental replication. The automated functional annotation provided by iGA greatly reduces the complexity of microarray results and facilitates the interpretation process. In addition, iGA can be used as a fast and efficient tool for the platform-independent comparison of a microarray experiment to the vast number of published results, automatically highlighting shared genes of potential interest. By applying iGA to a wide variety of data from diverse organisms and platforms we show that this approach enhances and accelerates the interpretation of microarray experiments.

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