We review methods for capturing differential coexpression, which can be divided into two cases by the size of gene sets: 1) two paired genes and 2) multiple genes. In the first case, two genes are positively and negatively correlated with each other under one and the other conditions, respectively. In the second case, multiple genes are coexpressed and randomly expressed under one and the other conditions, respectively. We summarize a variety of methods for the first and second cases into four and three approaches, respectively. We describe each of these approaches in detail technically, being followed by thorough comparative experiments with both synthetic and real data sets. Our experimental results imply high possibility of improving the efficiency of the current methods, particularly in the case of multiple genes, because of low performance achieved by the best methods which are relatively simple intuitive ones.

MOTIVATION: We address the issue of finding a three-way gene interaction, i.e. two interacting genes in expression under the genotypes of another gene, given a dataset in which expressions and genotypes are measured at once for each individual. This issue can be a general, switching mechanism in expression of two genes, being controlled by categories of another gene, and finding this type of interaction can be a key to elucidating complex biological systems. The most suitable method for this issue is likelihood ratio test using logistic regressions, which we call interaction test, but a serious problem of this test is computational intractability at a genome-wide level. RESULTS: We developed a fast method for this issue which improves the speed of interaction test by around 10 times for any size of datasets, keeping highly interacting genes with an accuracy of approximately 85%. We applied our method to approximately 3 x 10(8) three-way combinations generated from a dataset on human brain samples and detected three-way gene interactions with small P-values. To check the reliability of our results, we first conducted permutations by which we can show that the obtained P-values are significantly smaller than those obtained from permuted null examples. We then used GEO (Gene Expression Omnibus) to generate gene expression datasets with binary classes to confirm the detected three-way interactions by using these datasets and interaction tests. The result showed us some datasets with significantly small P-values, strongly supporting the reliability of the detected three-way interactions. AVAILABILITY: Software is available from http://www.bic.kyoto-u.ac.jp/pathway/kayano/bioinfo_three-way.html CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.