Neuronal apoptosis revealed by genomic analysis: integrating gene expression profiles with functional information

Abstract

Apoptosis is a key physiological response that occurs during development of the nervous system, resulting in the death of nearly half of the embryonic neuronal population. Aberrant apoptotic mechanisms are thought to contribute significantly to many neurological disorders including Alzheimer's disease. Although many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis, the complete spectrum of genes involved in distinct temporal domains is mostly unknown. To begin a comprehensive survey of the gene-based molecular mechanisms that underlie neuronal apoptosis, we have used the unprecedented experimental opportunities that genome sequences and the development of DNA microarray technology now provide to perform genome-wide expression analysis in different paradigms of neuronal apoptosis. In order to extract knowledge from gene expression information we have developed new informatics applications that enable clustering methods based on semantic characteristics, such as gene ontologies. This review will highlight the use of a genomic approach to identify the molecular program underlying neuronal apoptosis and illustrate how a semantic clustering method can be useful to extract more knowledge from microarray data.