Accurate, long read length, whole human genome sequencing under $100

描述（由申请人提供）：拟议研究的长期目标是设计和构建一个DNA测序系统，该系统可以在100美元以下对整个人类基因组进行测序，包括样品制备，并且该系统的产品成本远低于10,000美元。根据拟议研究开发的系统在成本上至少比招标目标好一个数量级，同时保持所有性能指标。在这方面，它将打破基因组医学的障碍。整个系统是基于消费者手机相机芯片上的光学DNA测序，通过传感器将DNA单个碱基的纳米级动态与宏观运动联系起来，无需使用荧光即可轻松成像，但只需使用单个普通白光LED。初步数据表明，该方法已能实现1,600个碱基的DNA读长和100个碱基片段的精确测序比对。虽然这是一个很好的开始，但第一阶段的工作将继续研究这种方法的准确性、读长和吞吐量限制。为了实现这一目标，需要在第一阶段构建图像处理和生物信息学等软件工具，同时我们还需要改进生物分析。如果成功，主要目标是在第一阶段结束时对微生物DNA （Ecoli）进行完全测序，从而对所提出的体系结构进行完全基准测试。在第一阶段之后，将使用商用手机相机芯片构建一个低成本的台式系统，并将用于执行全人类基因组测序，目标成本定义为本次申请的目标。

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is the design and construction of a DNA sequencing system that can sequence the whole human genome under $100 including sample preparation and with the cost of goods of the system well under $10,000. The system developed under the proposed research is at least an order of magnitude in cost better than the target of the solicitation while maintaining all performance metrics. In that respect it will break the barrier towards genomic medicine. The overall system is based on optically sequencing DNA on a consumer cell-phone camera chip by means of a transducer that relates the nanometer scale dynamics of single base of a DNA to a macro-motion that is easy to image without the use of fluorescence, but only with a single common white-light LED. Preliminary data shows that the proposed method can already achieve DNA readlength of 1,600 bases and accurate sequencing alignment of 100 base sections. While this is a great start, Phase I work will continue to investigate the accuracy and readlength and throughput limits of this approach. To achieve that, software tools such as image processing and bioinformatics need to be constructed at this first phase, while at same time we will need to improve the biology assays. If successful, the main goal is to completely sequence a microbial DNA (Ecoli) at the end of Phase I, and thus completely benchmark the proposed architecture. Beyond Phase I, a low cost benchtop system will be constructed using commercial cell-phone camera chips and will be used to perform sequencing of Whole Human Genome with the target cost defined as goal of this grant solicitation.