Polony Sequencing the Human Genome

描述（由申请人提供）：我们建议进一步开发和利用超高通量polony基因组测序，主要目标是在一周内以低于10,000美元的成本重新测序人类基因组。目前，这项技术很先进，但要达到我们的目标还需要进一步的进步。作为该项目的关键定量里程碑，我们将报告人类基因组序列，其“目标序列质量相当于或优于2002年12月发表的小鼠序列（Nature 420:520, 2002）”。该项目分为四个具体目标，主要是：(1)通过增加读取长度来改进polony测序技术，改进文库构建方案，增加测序反应中的头密度，(2)改进polony基因组测序显微镜的设计，(3)改进我们用于组装原始序列读取的计算工具，最后，(4)对肿瘤基因组重新测序，确定肿瘤发展过程中发生的体细胞突变。实现我们目标的进展已进入后期阶段。我们能够常规地对细菌基因组进行测序，我们即将对整个人类基因组进行测序，以达到所需的质量水平。此外，我们认为通过追求本文所描述的目标可以获得可观的回报。

DESCRIPTION (provided by applicant): We propose to further develop and utilize ultra-high throughput polony genome sequencing with the primary goal of re-sequencing the human genome in under one week at a cost of less than $10,000. Currently, the technology is well advanced, but further progress is needed to meet our goals. As the critical quantitative milestone of the project, we will report the sequence for a human genome with "a target sequence quality equivalent to, or better than, that of the mouse assembly published in December 2002 (Nature 420:520, 2002)". The project is divided into four specific aims, which are basically to (1) to improve the polony sequencing technology by increasing the read length, improve the library construction protocol, and increase bead density in the sequencing reactions, (2) improve the design of the polony genome sequencing microscope, (3) improve the computational tools that we have for assembling the raw sequence reads, and finally, (4) re-sequence a cancer genome and identify the somatic mutations that have occurred during tumor development. Progress towards our goals is at an advanced stage. We are able to routinely sequence bacterial genomes and we are on the verge of sequencing an entire human genome to the required quality level. Additionally, we feel that there are substantial rewards to be gained by pursuing the goals described herein.