Systematic approach to the analysis of gene function

摘要

In order to identify, validate, and prioritize potential therapeutic targets, it is advantageous to understand the roles that these potential therapeutic targets play within the biological systems network. Stimulation of specific sets, or matrices, of cells followed by multiple time point measurements are used to capture temporal changes exhibited by the different biochemical and genetic elements within the cells. The response of these elements to various stimuli are compared and correlated, thus identifying the functional linkages of various cellular components (for example, different genes and proteins) as different biochemical pathways are stimulated within the cell. Genetic responses are further correlated to phenotypic responses, thus providing a disease model context in which different genes play a role. The methods and cell matrices of the present invention provide a user with ways to decipher these biochemical and genetic functions, and thereby evaluate various cellular components as potential therapeutic targets. The methods and cell matrices are useful e.g., for simultaneously monitoring both the expression levels and functional state for any number of proteins in a cellular system. In addition, the methods and cell matrices of the present invention can be used, for example, to monitor the response of targeted cellular pathways to stimulation by one or more potential drug therapies. Furthermore, the methods and cell matrices are useful, for example, for evaluating potential drug candidates even when the therapeutic target has not been identified.