On the performance of methods for finding a switching mechanism in gene expression.

Abstract

We address an issue of detecting a switching mechanism in gene expression, where two genes are positively correlated for one experimental condition while they are negatively correlated for another. We compare the performance of existing methods for this issue, roughly divided into two types: interaction test (IT) and the difference of correlation coefficients. Interaction test, currently a standard approach for detecting epistasis in genetics, is the log-likelihood ratio test between two logistic regressions with/without an interaction term, resulting in checking the strength of interaction between two genes. On the other hand, two correlation coefficients can be computed for two experimental conditions and the difference of them shows the alteration of expression trends in a more straightforward manner. In our experiments, we tested three different types of correlation coefficients: Pearson, Spearman and a midcorrelation (biweight midcorrelation). The experiment was performed by using ~ 2.3 × 10(9) combinations selected out of the GEO (Gene Expression Omnibus) database. We sorted all combinations according to the p-values of IT or by the absolute values of the difference of correlation coefficients and then visually evaluated the top ranked combinations in terms of the switching mechanism. The result showed that 1) combinations detected by IT included non-switching combinations and 2) Pearson was affected by outliers easily while Spearman and the midcorrelation seemed likely to avoid them.