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Current Topics Workshop: Chemogenomics (May 8-10, 2007)

(partially supported by the College of Medicine)

Organizers: Paul Blower, Joe Verducci, John Weinstein, and Stan Young

Advances in high throughput chemogenomic profiling such as yeast deletion libraries and whole genome shRNA-based loss-of-function arrays for human and mouse genes promise to accelerate the discovery of potential drug targets and increase understanding of complex interactions between components of a biological system. Chemogenomics can be defined as the use of genomics to measure the system-wide effect of a compound on an intact biological system, either single cells or whole organisms. It combines high-throughput genomics or proteomic profiling with chemoinformatic and statistical analysis to study the response of a biological system to chemical compounds. Cellular response is measured by phenotypic readouts in a high-throughput assay. Chemogenomics also investigates the consequences of differential gene/protein expression on cellular response to compound treatment. For example, expression levels of membrane transporters can have a dramatic effect on compound potency.

Chemogenomics as a discipline has been molded by access to the suite of datasets related to a panel of 60 cancer cell lines from the National Cancer Institute (NCI-60). This is an unparalleled public resource for elucidating molecular targets and mechanisms of chemosensitivity/resistance, with cytotoxic potencies for >50,000 compounds, as well as mRNA profiles and proteomes. In addition, the NCI-60 repertory will soon include expression patterns of microRNAs which can resolve discordant relationships between mRNA and protein expression profiles. The response of cancers to drug treatment is a biological process that cannot be understood by studying individual genes or proteins in isolation. The NCI-60 datasets provide significant opportunities for large-scale datamining and applications of statistical modeling of drug potencies based on mRNA/protein/miRNA expression, alone or in combination with aspects of molecular structure of the drug candidates.

In this workshop, we will survey advances in experimental techniques for high throughput profiling, statistical design and assessment for association, and chemoinformatic techniques for large-scale datamining of compound-gene associations. Chemogenomics draws on many scientific disciplines, and this workshop is intended to foster cross-discipline understanding and lead to long-term collaborations among participants. Conference presenters and discussion leaders will include experimental molecular biologists as well as scientists specializing in statistics, chemoinformatics and drug discovery applications.