) The overall goal of this program remains the systematic and quantitative analysis of genome-wide patterns of gene expression in cancer. By using cDNA microarrays to study normal and cancer-derived human cell lines as well as tumors, a cumulative gene expression database will be expanded to increase the biological informativeness of gene expression patterns in cell lines, normal tissues and tumors. At the same time, such experiments will begin to characterize the biological roles of the many heretofore uncharacterized human genes on the arrays. A variety of experiments with cell lines are proposed whose results will facilitate biological interpretation of gene expression patterns found in tumors. Proposed experiments include studies of periodic gene expression in synchronized animal cells growing in culture; patterns of gene expression displayed by genes when stressed with starvation, heat, cold, radiation, etc; studies of changes in gene expression during long-term culture, and studies of gene expression patterns when cells are organizing themselves into rudimentary tissues. The program includes substantial improvements in the computational and analytical infrastructure, including further development of analytical algorithms as well as improved database, data archiving and data display systems. Finally, further technology development of the cDNA microarray technology is proposed.
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