A crucial component to the recent major advances in genomic research has been the uniting of advances in biology with those in computers, informatics and networking. As sequencing throughput has increased, the technological burden has shifted increasingly to analysis and informatics. This project was established to ensure that necessary computational tools and resources are available to the NIH community. An integrated system for the storage, management, analysis and viewing of cDNA microArray data has been developed to support the NCI Advanced Technology Center microArray facility. The mAdb (microArray database) system provides a secure data management system for gathering, storing, and managing experimental information and expression array data. A variety of Web accessible tools have been implemented to support the multiple analytical approaches needed to decipher array data in a more meaningful way. Important to the mAdb system design is compatibility with any platform (Unix, Windows or Macintosh) capable of running an Internet Browser. We have taken an evolutionary developmental approach to designing and implementing the mAdb system, which provides for continuous evaluation, improvement, flexibility and quick turn around. In addition, tools for mining UniGene for Tissue specific Gene sets and that allow comparison of various microArray Gene sets have been made available to the community. A natural extension of mAdb has been the inclusion of additional data resources. This includes supporting information from various data sources (e.g. Gene Ontology, GenBank, LocusLink, UniGene, KEGG Pathways, Biocarta Pathways and GeneCards) to enable drilling down into the rapidly expanding biological knowledgebase. In order to have effective use of the informational resource developed to support micorArray analysis, ongoing user training and support is provided through CIT facilities for this collaborative effort. While on going development of new and improved analysis tools continues, the mAdb system is in routine service, supporting over 900 NCI researchers and collaborators and containing over 30,000 microArray experiments. A critical design element for the mAdb system was to accommodate scalability to allow expansion to support other ICDs. The design allows us to support separate WEB servers serving different user communities from a single code base. The mAdb system has been set up on separate WEB servers to support users of the NIAID microArray core facility and the Lymphoma Leukemia Molecular Profiling Project consortium. Preliminary discussions and exploratory planning to add support for the NIA microArray core facility have been undertaken. The Lymphoma/Leukemia Molecular Profiling Project is using Lymphochip cDNA microArrays to define the gene expression profiles of all types of human lymphoid malignancies. One primary goal of this Project is to redefine the classification of human lymphoid malignancies in molecular terms. A second major goal is to define molecular correlates of clinical parameters that can be used in prognosis and in the selection of appropriate therapy for these patients. As members of the international LLMPP consortium, we provide the Informatics development and support this project. Computational genetic linkage analysis software packages are widely used at NIH for the precise mapping of potential disease genes. This software is extremely computer resource-intensive and complex to use and maintain. We have assisted NIH laboratories performing linkage analysis by providing needed software on shared, high-performance computing platforms, as well as creating streamlined procedures to use the software. One application of these techniques, in collaboration with the National Center of Biotechnology Information and the National Cancer Institute, used two new sets of genetic marker data and the software packages CRI-MAP and FIRSTORD to extend and significantly enrich the feline genomic map. Genetic research into inherited diseases has been advanced by the continuing collaboration with the National Center for Biotechnology Information to build upon a comprehensive database of a population of North American Anabaptists. This database was greatly enlarged by the addition of a new genealogy source. The database was used to investigate the associations between inbreeding, family size, interbirth intervals, early death, and twinning.
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