Development of Web-driven Bioinformatic Platform for Microarrays

The objective of this effort is to create an innovative bioinformatics platform for microarray data management and analysis. This platform will overcome the following limitations inherent in current microarray systems: (1) current systems typically do notaddress all types of array data, (2) current systems do not record the context of the samples, which hinders scientific and statistically relevant queries of the data, and (3) current systems do not track computational processes, which hampers dataanalysis. In order to take advantage of microarrays and manage the massive volume of data produced by them, scientists must have bioinformatics platforms like the one we are developing for this research. We propose to couple a highly sophisticatedLaboratory Information Management System (LIMS) to a pioneering analysis information management system (AIMS) that executes computational processes and interfaces with external bioinformatics tools as well as databases. The integration of LIMS and AIMSwill produce dramatic benefits for researchers throughout the DOD's Defense Technology Area Plan in Infectious Diseases of Military Importance by improving research quality and decreasing time to biological discovery. Some of the technologies used in thisresearch were developed by 3rd Millennium for an Advanced Technology Program (ATP) grant (see Related Work section).The bioinformatics platform we are developing will benefit both the government and the private sector in drug development, toxicologystudies, and disease treatment by improving research quality and decreasing time to biological discovery. For example, the platform will aid disease treatment by facilitating the development of gene expression molecular phenotype classifiers for diseasestates. These classifiers can be used to match drugs to the diseases against which they will be the most effective. The search engine we implemented in Phase 1 of the research and will develop further in Phase 2 can aid in the construction of suchclassifiers. The sophisticated engine can also help in drug development by identifying genes that are suitable drugable targets and have altered expression profiles in the disease state relative to the healthy state. Also, databases of expression profileslike the one we implemented in Phase 1 are already being used in drug toxicology studies to determine if candidate drugs have molecular phenotypes that are known to be toxic. Expression profile databases have also shown utility in identifying the functionof genes that lack annotations. This is especially helpful for researchers who are working with organisms that have poorly annotated genomes like the disease causing agents Plasmodium falciparum (malaria) and Bacillus anthracis (anthrax). In order torealize the full potential of functional genomic technologies like microarrays, researchers throughout the DOD and private sector need bioinformatics platforms like the one we successfully developed for Phase 1 of the research and will develop further inPhase 2. Finally, technologies developed for this proposal will also be extremely effective for the management and analysis of other functional genomic data such as proteomic and metabolic data.