The primary goal of Core C will be to provide access to transcriptional profiling technologies to examine differential mRNA expression in the scope of endothelial cell heterogeneity and to delineate the mechanisms underlying site-specific phenotypes studied by the individual projects. The main objectives of the core will be to consult and train on functional genomics and bioinformatics, to provide standardized methods for quality control and validation of microarray experiments, to offer experienced onsite staff to perform microarray experiments and to analyze the data, to implement, update, and develop bioinformatics and biostatistics software tools for microarray analysis and data mining, and to develop a standardized database and interactive research portal. The core will label the cRNA probes, hybridize microarrays as well as provide a comprehensive analysis of the microarray data using biostatistical and bioinformatics software tools. Data generated by the core will be uploaded to the Research Portal and incorporated into a database for further analysis and querying by the individual investigators for hypothesis generation. The Core will establish the Endothelial Cell Heterogeneity Research Portal (ECHRP) to provide web-accessible data entry, annotation, cataloging facilities and state-of-the-start bioinformatics analyses. In addition, the core will develop new bioinformatics tools for data analysis and integration of metadata with the aim to build and simulate biological pathways. This will enable researchers from all Projects to maximally utilize the expression data sets to determine functional dependencies among the known and unknown genes and direct further biological validation of these putative dependencies. This critical biological validation step is described in each of the respective Project proposals. The facility will use Affymetrix GeneChip arrays of murine and human expressed sequences. By providing these services as a core function, we aim to save time and money and to establish quality controls and standardized procedures and reagents, which will lead to standardized data sets that can be compared and shared by different investigators in the program. In addition, integration of data sets from the different projects may by itself generate new insights not visible in individual data sets. The core will facilitate to integrate the wealth of data generated by the individual projects beyond the data generated by the microarray experiments.
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