SBIR Phase II: Rapid Pathogen Diagnostics and Biosurveillance using Multiplexed High-throughput Sequencing

小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力是提高我们抗击对农业产量造成负面影响的传染病的能力，并降低全球粮食生产和分配系统的效率。这项创新将利用高通量测序和生物信息学的力量，提供一种病原体识别和监测工具，对已知和未知的感染性病原体证明有效，从而加强对科学和技术的了解。该平台快速、灵敏、经济高效，可用于任何动物样本，以检测几乎所有可能的微生物，甚至是以前从未表征过的微生物。数百个样本可以在不依赖已知的微生物遗传/基因组数据的情况下进行快速筛选。2012-2017年，全球分子诊断市场的复合年增长率(CAGR)预计将超过14%，其中传染病检测是领先的应用，占有率为26%，因此该项目的商业机会巨大。此外，这项提议寻求建立一个基本的信息学基础设施，再加上样品制备的改进，将有助于对几个样品进行可扩展的高通量分析。目前的诊断方法依赖于已知的目标微生物遗传学，并以存在/不存在已知目标序列的形式提供有限的信息。SBIR第一阶段有助于降低与基于DNA测序和贝叶斯统计的高通量无偏见病原体检测平台相关的技术风险。在追求标准化和验证我们的元基因组病原体识别平台的过程中，该项目建议：1)提高病毒检测能力和准确性，2)开发新功能，3)将第一阶段和第二阶段的进展整合到一个集成的内部网络可访问界面中。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to improve our ability to fight infectious diseases that negatively impact agricultural yields and reduce the efficiency of global food production and distribution systems. This innovation will enhance scientific and technological understanding by leveraging the power of high-throughput sequencing and bioinformatics to provide a pathogen identification and surveillance tool with demonstrated efficacy against known and unknown infectious agents. This platform is fast, sensitive, and cost-effective, and can be used for any animal sample to detect virtually all possible microbes even microbes that have never before been characterized. Hundreds of samples can be rapidly screened without relying upon known genetic/genomic data of microbes. The global molecular diagnostics market is expected to grow at a compound annual growth rate (CAGR) of over 14% from 2012 to 2017, with infectious disease testing being the leading application at 26% share, therefore the commercial opportunity of this project is vast.The proposed project follows up on the validation of the diagnostic platform (SBIR Phase I) and delves deeper into improving virus detection and genetic data generation. In addition, this proposal seeks to develop a basal informatics infrastructure that together with sample preparation improvements will be conducive of scalable, high-throughput analysis of several samples. Current diagnostic methods rely on what is already known about target microbe genetics, and provide limited information in the form of presence/absence of a known target sequence. The SBIR Phase I was instrumental to lowering the technical risks associated with a high-throughput unbiased pathogen detection platform based on DNA sequencing and Bayesian statistics. In the pursue of standardizing and validating our metagenomics pathogen identification platform, this project proposes to: 1) improve viral detection capabilities and accuracy, 2) develop new functionalities, and 3) incorporate Phase I and Phase II advances into an integrated in-house web-accessible interface.