Technology Implementation This proposal is a renewal application for the Stanford Genome Technology Center Grant. The promise of Whole Genome Sequencing (WGS) is now realized, and SGTC has pioneered many of the technological breakthroughs in sequence automation and high-throughput oligonucleotide synthesis that have made this a reality. Two big challenges in translational genomic medicine remain. The first is that the human organism is not a single genome, but a collection of cells with slightly varying genomes, and those variations are often very important in disease. The second is that not all regions of the genome are equivalent in disease causing potential or equally amenable to sequencing. In this third tier of the proposal. Technology Implementation, we will focus on making technologies that we have developed at SGTC accessible to a wider community of biomedical researchers and clinicians. We have developed several new technologies that are able to selectively capture highly multiplex, targeted regions ofthe genome in very small cell populations and in pools, and sequence them with very high fidelity. Successful implementation requires that the technology be: 1) robust and reproducible with low barriers for practical implementation in translational and clinical studies;and 2) low cost, such that clinical studies of large populations are done economically. We will apply targeted resequencing methods to identify rare genetic variants in cancer and provide accurate HLA typing for transplantation, and a transcriptome microarray method tailored for the cost-effective analysis of clinical samples to investigate gene expression changes. The resulting discoveries from these efforts will improve the quality of patient care by enabling biomedical researchers and clinicians to personalize treatments to each individual.
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