Construction and evaluation of yeast expression networks by database-guided predictions.

Abstract

DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We performed microarray experiments to elucidate the transcriptional networks, which are up- or down-regulated in response to the expression of toxic polyglutamine proteins in yeast. Such experiments initially generate hit lists containing differentially expressed genes. To look into transcriptional responses, we constructed networks from these genes. We therefore developed an algorithm, which is capable of dealing with very small numbers of microarrays by clustering the hits based on co-regulatory relationships obtained from the SPELL database. Here, we evaluate this algorithm according to several criteria and further develop its statistical capabilities. Initially, we define how the number of SPELL-derived co-regulated genes and the number of input hits influences the quality of the networks. We then show the ability of our networks to accurately predict further differentially expressed genes. Including these predicted genes into the networks improves the network quality and allows quantifying the predictive strength of the networks based on a newly implemented scoring method. We find that this approach is useful for our own experimental data sets and also for many other data sets which we tested from the SPELL microarray database. Furthermore, the clusters obtained by the described algorithm greatly improve the assignment to biological processes and transcription factors for the individual clusters. Thus, the described clustering approach, which will be available through the ClusterEx web interface, and the evaluation parameters derived from it represent valuable tools for the fast and informative analysis of yeast microarray data.