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DOEs transition to production sequencing has been based largely on gel electrophoresis, with data acquisition by laser-induced fluorescence. However, this in no way decreases the necessity for innovative long-term basic research in the area of instrumentation support for genome studies. In this context, OBER is refocusing its current Genome Instrumentation Program, taking stock of current progress and considering likely future needs. [See related article on Jason Review.] To complete the human genome sequence within the available budget and time, substantial improvements in existing sequencing methods would be advantageous. Further, OBER places a strong emphasis on research directed to completely new approaches to genomic analysis. After 2005 the ongoing need will be for fast and cost-effective determination of DNA sequence to compare sequences among individual humans and also to determine the genomes of numerous organisms of biomedical and commercial interest. Additionally, with the continuing acquisition of this remarkable base of biological data, high-throughput experimental tools will be required to assist in a practical and useful understanding of gene function. Specific Instrumentation Goals * Approaches to determining DNA sequence more rapidly, accurately, and economically, particularly to increase current maximum read lengths at least 2.5 times to 2000 to 2500 bases. * Instrumentation that integrates and more thoroughly automates DNA sequence determination (e.g., sample preparation, loading, and analysis) and data analysis. Priority will be placed on approaches that emphasize miniaturization and microfabrication. * Approaches that (1) verify a previously determined DNA sequences accuracy without having to redetermine its entire sequence and (2) provide economical error-checking and proofreading of newly determined DNA sequence. * Tools that enable efficient comparison of a known DNA sequence with a related but previously undetermined DNA sequence. * Techniques for determining the functions of large numbers of genes in parallel, particularly those that match the speed and volume of DNA sequence determination. This solicitation was intended to stimulate research that tests the applicability of concepts unrelated to the standard instrumentation for gene sequencing. The emphasis is on basic science that will enable genomic studies in the next century, when genomic data will be widely available and the appetite for new data will be undiminished. Robust tools for using this information within new quantitative, mechanistic, and predictive biology will be paramount. Work supported within the redirected program will hasten the arrival of an epoch when ideas and experiments requiring genome-scale data are within the scope of investigator-initiated, hypothesis-driven science. |
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