This grant application proposes to expand and extend the services of the Massachusetts General Hospital Microarray Facility to investigators within the greater Boston community who are supported by grants awarded by the National Heart Lung Blood Institute. Although microarray analysis has opened up the potential to explore the interactions of large numbers of genes simultaneously, the obstacles to successful execution of this work are substantial. One of the chief hurdles to microarray analysis has been cost. Given the imperative to repeat assays in order to ensure reproducibility, this cost has made it difficult, if not impossible, for the typical academic lab to afford to conduct complex microarray studies. By using oligonucleotides synthesized by the MGH Oligonucleotide Facility and arraying our own oligos, we expect to lower substantially this cost barrier. Other factors that have impeded progress in microarray work have included problems with clone/gene availability and/or contamination when using spotted cDNAs, lack of probe or array reproducibility, and insufficient access to bioinformatics expertise in the analysis of very large data sets. Through our commitment to the use of spotted oligonucleotides as the probe sequences on microarrays, the issue of clone availability and contamination should be resolved. Bioinformatics as well as biological solutions to the problem of array reproducibility have been addressed in this grant application. Finally, with the recruitment of several leading local biostatisticians and bioinformaticians as co-investigators or consultants, the MGH Microarray Facility has assembled the requisite expertise and effort to facilitate a collaborating investigator's ability to analyze the large data sets generated by microarray techniques. The resources of this grant will be devoted to supporting the extensive community of NHLBI funded investigators at the major teaching hospitals and universities in the Boston area, including many younger investigators who have not previously had access to this important but costly research tool.
