Modeling nonlinearity in dilution design microarray data

Dilution design (Mixed tissue RNA) has been utilized by some researchers to evaluate and assess the performance of multiple microarray platforms. Current microarray data analysis approaches assume that the quantified signal intensities are linearly related to the expression of the corresponding genes in the sample. However, there are sources of nonlinearity in microarray expression measurements. Such nonlinearity study in the expressions of the RNA mixtures provides a new way to analyze gene expression data, and we argue that the nonlinearity can reveal novel information for microarray data analysis. Therefore, we proposed a statistical model, called proportion model, which is based on the linear regression analysis. To approximately quantify the nonlinearity in the dilution design, a new calibration, beta ratio (BR) was derived from the proportion model. Furthermore, a new adjusted fold change (adj-FC) was proposed to predict the true FC without nonlinearity, in particular for large FC.