The primary goal of Core D is to provide access to complementary transcriptional profiling technologies in order to examine differential mRNA expression during spatial and temporal regulation of angiogenesis in different model systems studied by the individual projects. The main objectives of the core will be to (1) consult and train on functional genomics and bioinformatics, (2) provide standardized methods for quality control and validation of microarray experiments, (3) offer experienced onsite staff to perform microarray experiments and to analyze the data, (4) implement, update, and develop bioinformatics and biostatistics software tools for microarray analysis and data mining, and (5) develop a standardized database and interactive research portal. The core will label cRNA probes, hybridize Affymetrix and customized arrays, and provide comprehensive analysis of the microarray data using biostatistical and bioinformatic 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 testing and generation. Specifically, the Core will establish the Angiogenesis Research Portal (ARP) to provide web-accessible data entry, annotation, cataloging facilities and state-of-the-art bioinformatics analyses for investigators in the several projects. The core is also developing new bioinformatics tools for data analysis and integration of metadata with the aim to build biological pathways. This will enable researchers from all Projects to use maximally the expression data sets to determine functional dependencies among the known genes and, as desired, Expressed Sequence Tags (ESTs) and direct further biological validation of these putative dependencies. For this Program Project the facility will make primary use of Affymetrix GeneChip arrays of murine and human expressed sequences although we have the capacity to generate customized focused microarrays on glass slides spotted with oligonucleotides. Services to be provided are: 1. Establish a web-accessible Angiogenesis Research Portal (ARP) for data entry and analysis. 2. Provide statistical and other advice with regard to experimental design. 3. Provide standardized RNA expression data from biological samples provided by the individual projects. 4. Develop and make use of """"""""noise-aware"""""""" Benchmark Data Sets (BDS) for normal murine tissues and cells. 5. Aid in hypothesis generation by providing and making use of bioinformatics techniques to identify functional dependencies. Providing these services as a core function will save time and money and establish quality controls and standardized procedures and reagents which will lead to standardized data sets that can be compared and shared by all investigators in the program. Integration of data sets from the different projects may also generate new insights not visible in individual data sets.
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