Technolgy Implementation

项目总结：技术实施 这项提案是斯坦福大学基因组技术中心拨款的续签申请。全基因组测序(WGS)的前景现在已经实现，SGTC在序列自动化和高通量寡核苷酸合成方面取得了许多技术突破，使其成为现实。翻译基因组医学仍然面临两大挑战。首先，人类有机体不是一个单一的基因组，而是基因组略有变化的细胞的集合，而这些变化在疾病中往往非常重要。第二，并不是基因组的所有区域在引起潜在疾病或同样适合测序的情况下都是等同的。在这份提案的第三层。在技术实施方面，我们将专注于使更广泛的生物医学研究人员和临床医生社区能够使用我们在SGTC开发的技术。我们已经开发了几种新技术，能够选择性地在非常小的细胞群体和池中捕获基因组的高度多元化的目标区域，并以非常高的保真度对它们进行测序。成功的实施要求该技术：1)在转化性和临床研究中的实际实施门槛低、健壮和可重复性；以及2)低成本，以便以经济的方式完成大量人群的临床研究。我们将应用有针对性的重测序方法来识别癌症中罕见的基因变异，并为移植提供准确的HLA配型，以及为临床样本进行成本效益分析而量身定做的转录组微阵列方法，以研究基因表达的变化。这些努力所产生的发现将使生物医学研究人员和临床医生能够为每个人提供个性化的治疗，从而提高患者护理的质量。

Project Summary: 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.