Large Scale Sequencing and Analysis of Genomes

基因组学正处于一个科学机遇和技术发酵的非凡时刻。DNA 序列信息正成为研究生物学问题的一个越来越强大的工具， 这些技术有望大幅降低DNA测序的成本，从而进一步扩大其应用范围。 到达。与此同时，科学和技术的前进道路有许多不确定性和障碍。 出于这些原因，NHGRI寻求支持基因组中心提供科学和 在这个激动人心的过渡时期保持技术领先地位。 这项建议有三个具体目标： 目标1。当前的技术。我们建议使用现有的技术来运营一个最先进的基因组中心 测序技术，继续我们15年的高通量，低成本和灵活性的跟踪记录。我们 年吞吐量将超过610亿个基数，到年底成本将降至0.29美元/kQ 20基数 4.该能力将有可能在鸟枪测序中灵活分配， 排序和整理/改进。 目标二。新技术同时，我们的目标是用新的， 颠覆性技术，目标是大幅降低成本，提高产量。在第一 今年，我们将以足够的规模运行两个新的测序平台（454和Solexa），以了解它们的功能。 真正的性能、成本和实用性，并产生有价值的数据。根据结果，我们的目标是扩大规模 一个或两个平台尽快。 这项工作需要的不仅仅是简单地在生产规模上实施新的仪器，尽管这是一个挑战。 实质性挑战。更大的挑战是，这两个平台目前不适合NHGRI的关键 基因组应用，即基因组组装和定向重测序。我们将开发全套 实验室和计算工具，以适应这些关键应用的技术。 我们的目标是在资助结束时，这些关键应用程序的成本降低30倍以上 期 目标3。科学领导力。我们将继续作为科学的智力资源， 社区，通过开创新的方法，利用DNA序列来解决重要的生物医学问题， 并与社区合作，迅速传播想法、方法和数据。

Genomics stands at a remarkable moment of scientific opportunity and technological ferment. DNA sequence information is becoming an increasingly powerful for investigating biological question, and new technologies promise to decrease dramatically the cost of DNA sequencing and thereby further expand its reach. At the same time, the scientific and technological path forward has many uncertainties and obstacles. For these reasons, NHGRI seeks to support genome centers with the ability to provide both scientific and technological leadership through this exciting period of transition. This proposal has three specific aims: Aim 1. Current technology. We propose to operate a state-of-the-art genome center using current sequencing technology, continuing our 15-year track record of high throughput, low cost and flexibility. Our annual throughput will exceed 61 billion bases, with costs decreasing to $0.29/kQ20 base by the end of Year 4. The capacity will have the potential to be allocated flexibly across shotgun sequencing, targeted sequencing and finishing/improvement. Aim 2. New technology. In parallel, we aim to completely replace the current generation with new, disruptive technologies, with the goal of dramatically decreasing cost and increasing output. During the first year, we will operate two new sequencing platforms (454 and Solexa) at sufficient scale to understand their true performance, cost and utility and to produce valuable data. Based on the results, we aim to scale-up one or both platforms as soon as possible. This work requires more than simply implementing new instruments at production scale, although this is a substantial challenge. The greater challenge is that the two platforms are not currently suited to NHGRI's key genomic applications ¿ namely, genome assembly and directed re-sequencing. We will develop the full set of laboratory and computational tools required to adapt the technologies to these key applications. Our goal will be to achieve a cost reduction of >30-fold in these key applications by the end of the grant period. Aim 3. Scientific leadership. We will continue to serve as an intellectual resource for the scientific community, by pioneering new approaches for using DNA sequence to solve important biomedical problems and by working with the community to rapidly disseminate ideas, methods and data.