Yevgeny Doctor & Guy Nimrod CS-LS 2nd year, Hebrew University of Jerusalem Israel Gene Expression : Clustering Abstract The rapid advance of genome-scale sequencing has driven the development of methods to exploit this information by characterizing biological processes in new ways. Microarrays are one of the latest breakthroughs in molecular biology as a tool for monitoring the expression level of each gene in the cell. Their applications embody much of what is implied by the term ‘genomics’ – they are broad in scope, large in scale and take advantage of all available sequence information for experimental design and data interpretation in pursuit of biological understanding. In order to process the large amounts of information produced by this technique, new algorithmical approaches were developed, and we will present one of them – clustering. This method organizes genes in clusters according to similarity in patterns of gene expression, and displays the data graphically in a way that is intuitive for biologists. The clustering of the genes can be used to gain understanding of the functions of the genes and their regulation, as well of global cellular processes. We present two large-scale experiments in yeast that used the methods described above. The first research explores the genomic expression patterns in yeast in response to diverse environmental transitions. A large set of genes (~900) showed a similar drastic response to almost all environmental changes, and there were additional features of the genomic responses specialized for specific conditions. This work gives a partial sketch of the complex regulation of the environmental stress response of yeast and suggests several hypotheses for further investigation. The second work uses the expession pattern analysis in order to identify and characterize genes whose transcript levels vary periodically within the cell cycle. The authors explore the functional properties of the gene clusters, and look for known and new promoter elements regulating those genes. The resulting data gives a partial picture of the circuitry of the transcriptional controls in the cell cycle. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell. 1998 Dec;9(12):3273-97. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell. 2000 Dec;11(12):4241-57. Lockhart DJ, Winzeler EA. Genomics, gene expression and DNA arrays. Nature. 2000 Jun 15;405(6788):827-36.