Can molecular mechanisms of biological processes be extracted from expression profiles? Case study: endothelial contribution to tumor-induced angiogenesis.

Whereas the genome contains all potential developmental programs, expression profiles permit the determination of genes that are actively transcribed under defined physiological conditions. In this article, the idea of extracting biological mechanisms from expression data is tested. Molecular processes of the endothelial contribution to angiogenesis are derived from recently published expression profiles. The analysis reveals the sensitivity limits of experimental detection of transcriptional changes and how sequence-analytic techniques can help to identify the function of genes in question. We conclude that the transcripts (http://mendel.imp.univie.ac.at/SEQUENCES/TEMS/) found to be up-regulated in angiogenesis are involved in extracellular matrix remodeling, cellular migration, adhesion, cell-cell communication rather than in angiogenesis initiation or integrative control. Comparison with tissue-specific patterns of EST occurrence shows that, indeed, the presumptive tumor-specific endothelial markers are more generally expressed by cell types involved in migration and matrix remodeling processes. This exemplary study demonstrates how bioinformatics approaches can be helpful in deriving mechanistic information from diverse sources of experimental data. Copyright 2001 John Wiley & Sons, Inc.