Gene expression measurement using cDNA and oligo arrays is exploding in popularity, yet many technical problems remain. In parallel, high throughput methods for measuring protein concentrations are being developed. One of the more challenging problems results from the large volume of data generated in these experiments. Image capture, processing, interpretation and quantification remain as important fundamental issues. Quality control and experimental design must be carefully addressed. Numerous statistical, image processing and bioinformatics issues remain problematic. Accordingly, these projects seek to address such problems. In a major NIH-wide project, we maintain a database for storage, retrieval and analysis of Affymetrix oligo-based microarrays, NIHLIMS. As part of this collaboration, we are creating a data analysis pipeline and bioinformatics toolset, including both commercial and freely available software. The database currently stores information from over 2000 microarrays. Our web-based analysis (A-SCAN) and downloadable tool set (MSCL Analyst's Toolbox) are now mature, widely tested and applied in numerous studies. Working with laboratories in NCI, CC, NHLBI, NINDS, NIAID, NHGRI, NICHD, NIA, NIDDK, NIDA we have developed, customized and applied software for the analysis of microarray based studies. In one of several major studies with the Critical Care Medicine Department, CC, we have designed and analyzed a study of the genomics of recovery and subsequent rejection of heart transplants in a novel animal model. The goal is to identify markers of rejection which could eventually be used in monitoring recovery from transplant in humans. We have developed a novel statistical tool, GO-SCAN for analysis of gene annotations associated with differentially expressed genes. The tool provides several compact visualizations of annotation space, and has been successfully applied in the analysis of an endotoxin response study in which over 1,000 differentially expressed genes were identified. A web-version of the tool is now also available. In an ongoing study of pineal function with investigators of NICHD, we identified several hundred genes which manifest circadien variation in rats, and for which measurement of homologs in human and monkey were feasible. Interestingly, pineal function in primates appears to be controlled in a very different way from rodents. In one of two proteomics initiatives, we collaborated with investigators in CCMD to apply mass-spectroscopy for identification of novel entities as possible markers of infection in BAL (bronchial alveolar lavage) fluid. A time course study of normal volunteers exposed to endotoxin demonstrated a significant number of varying spectroscopic peaks, which were subsequently identified molecularly. A study of samples from ARDS (acute respiratory distress syndrome) patients confirmed most of these results. Methods previously developed by this lab for reverse-phase proteomic arrays were applied in studies undertaken by investigators of Laboratory of Molecular Pharmacology, NCI. MSCL staff participated in a nationwide collaboration to advance sepsis research, a topic of high interest to critical care medicine. A major invited lecture was presented at the 2nd Symposium on Functional Genomics of Critical Illness and Injury. The MSCL staff frequently provides advice and guidance to several Institutes and Laboratories as they apply new microarray , proteomic and bioinformatics techniques. In particular, NHLBI, NICHD, NINDS, NIDA and NIDDK have requested and received extensive consultations in this area. MSCL staff also participate in the NIH-wide Biomedical Information Science and Technology Initiative (BISTI) Consortium serve as the focus of biomedical computing issues at the NIH
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