From microarray to biological networks: Analysis of gene expression profiles.

Powerful new methods, such as expression profiles using cDNA arrays, have been used to monitor changes in gene expression levels as a result of a variety of metabolic, xenobiotic, or pathogenic challenges. This potentially vast quantity of data enables, in principle, the dissection of the complex genetic networks that control the patterns and rhythms of gene expression in the cell. Here we present a general approach to developing dynamic models for analyzing time series of whole-genome expression. The parameters in the model show the influence of one gene expression level on another and are calculated using singular value decomposition as a means of inverting noisy and near-singular matrices. Correlative networks can then be generated based on these parameters with a simple threshold approach. We also demonstrate how dynamic models can be used in conjunction with cluster analysis to analyze microarray time series. Using the parameters from the dynamic model as a metric, two-way hierarchical clustering could be performed to visualize how influencing genes affect the expression levels of responding genes. Application of these approaches is demonstrated using gene expression data in yeast cell cycle.