Regulatory sequence analysis: application to the interpretation of gene expression.
Microarray technologies for measuring mRNA abundances in cells allow monitoring of gene expression levels for tens of thousands of genes in parallel. By measuring expression responses across hundreds of different conditions or timepoints a relatively detailed gene expression map starts to emerge. Using cluster analysis techniques, it is possible to identify genes that are consistently coexpressed under several different conditions or treatments. These sets of coexpressed genes can then be compared to existing knowledge about biochemical or signalling pathways, the function of unknown genes can be hypothesised by comparing them to other genes with characterised function, or from trends in expression profiles in general - why cell needs to transcribe or silence the genes during particular treatment. The regulation of genes on the DNA level is largely guided by particular sequence features, the transcription factor binding sites, and other signals encaptured in DNA. By analyzing the regulatory regions of the DNA of the genes consistently coexpressed, we can discover the potential signals hidden in DNA by computational analysis methods. The prerequisite for this kind of analysis is the existence of genomic DNA sequence, knowledge about gene locations, and experimental gene expression measurements for a variety of conditions. This article surveys some of the analysis methods and studies for such a computational discovery approach for yeast Saccharomyces cerevisiae.
Vilo
J
J
European Bioinformatics Institute EBI, EMBL Outstation - Hinxton, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK. vilo@ebi.ac.uk
Kivinen
K
K
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000706:statistics & numerical data / Q000639:trends