High throughput analysis of differential gene expression

Elucidation of the changes in gene expression associated with biological pr ocesses is a central problem in biology. Advances in molecular and computat ional biology have led to the development of powerful, high-thoughput metho ds for the analysis of differential gene expression. These tools have opene d up new opportunities in disciplines ranging from cell and developmental b iology to drug development and pharmacogenomics. In this review, the attrib utes of five commonly used differential gene expression methods are discuss ed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene exp ression (SAGE). The application of EST sequencing and microarray hybridizat ion is illustrated by the discovery of novel genes associated with osteobla st differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax- 6. These and other examples illustrate the power of genomics for discoverin g novel genes that are important in biology and which also represent new ta rgets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, an d that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success. (C) 1998 Wiley-Liss, Inc.