Microarray gene expression profiling is performed in many laboratories, resulting in the rapid data accumulation in public repositories. However, due to the existence of different technology platforms and the lack of standard experimental protocols, systematic variation among data sets often exceeds the capability of statistical normalization. Currently, there is an urgent need for methodology to integrate cross-platform microarray data. This proposal addresses this need.
We aim at developing novel computational and statistical methods to integrate cross-platform microarray data. Specifically, we will (1) detect recurrent expression patterns across many microarray datasets; (2) perform functional and transcriptional annotation for multiple genomes; (3) predict transcription regulators for higher eukaryotic genes without prior information on protein-DNA binding sites; and (4) identify genetic networks that are signatures of diseases. Using our approach, we are in a position to extract an order of magnitude more information for any genome for which massive microarray data is available. We will perform """"""""context-specific"""""""" functional and transcriptional annotation for the genomes of yeast (S. cerevisiae), worm (C. elegans), fly (D. melanogaster), plant (A. thaliana), mouse (M. musculus), rat (R. norvegicus) and human (H. sapiens). That is, we will conditionally annotate the functions/regulations of genes, depending on which set of other genes they are interacting with and under which sets of conditions such interactions occur. When releasing our prediction results, we will attach to each annotation the necessary context information. Finally, we will develop a software package ARRAYMINEfor biologists to perform integrative analysis of cross-platform microarray data. Our algorithms and software will significantly facilitate the re-use of the vast amount of existing microarray data, reduce the necessity to generate new data, and improve our understanding of cellular functions and networks under a variety of perturbations.
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