SBIR Phase I: Delving Deeper into the Proteome

这个小型企业创新研究(SBIR)第一阶段项目试图证明一种从人体体液样本中去除大量蛋白质的新方法的概念验证。如果成功，建议的方法可能会改变新的蛋白质生物标记物的搜索和开发。识别人体体液中的稀释蛋白质生物标记物是困难的。可能有成千上万种独特的蛋白质，它们的浓度可能会在10个数量级上有所不同。该方法由通用仪器和相关试剂组成，旨在进行样品前处理步骤，以去除丰富的蛋白质，同时保留稀释的蛋白质，从而压缩样品的动态范围。它可以从今天常规使用的样本量扩大到多个数量级的大小，这对发现稀释蛋白质生物标记物非常重要。最后，该方法以浓缩和纯化蛋白质为前端，为传统的发现新生物标志物的方法：二维凝胶电泳法(Difference Gel Electric)和自下而上的蛋白质组学方法准备样本。这个项目的更广泛的影响/商业潜力是增加蛋白质诊断在个性化医学中的成功使用，这在药物开发、靶向和部署方面发挥着重要作用。蛋白质组学的潜在力量被人体体液样本的复杂性冲淡了。一旦开发出有效的前处理方法，选择性地去除丰富的蛋白质，人们就可以更深入地研究蛋白质组，以发现可能是疾病生物标志物的更稀薄的物种。这有可能大大提高蛋白质组学数据的质量，依赖于生物标记物发现数据。反过来，这将有助于加快新药上市速度，瞄准适当的临床人群，并有助于监测疾病进展。这些都可能对个性化医疗和公共健康产生深远的影响。

This Small Business Innovation Research (SBIR) Phase I project seeks to demonstrate proof-of-concept for a new method that removes abundant proteins from human fluid samples. If it is successful, the proposed method potentially could transform the search for and development of new protein biomarkers. Identifying dilute protein biomarkers in human fluids is difficult. There can be hundreds of thousands of unique proteins that can vary in concentration over 10 orders of magnitude. The proposed method, comprising a general-purpose instrument and allied reagents, is intended to perform sample pretreatment steps to remove abundant proteins while retaining dilute proteins, and thereby compress the dynamic range of the sample. It can be scaled from sample volumes used routinely today, to many orders of magnitude larger, which is important to uncover dilute protein biomarkers. Finally, the method concentrates and purifies proteins as a front end to prepare samples for the traditional methods used to discover new biomarkers: 2D gel electrophoresis (Difference Gel Electrophoresis) and bottom-up proteomics methods. The broader impact/commercial potential of this project is to increase the successful use of protein diagnostics in personalized medicine, which is assuming a major role in drug development, targeting and deployment. The potential power of proteomics is diluted by the complexity of human fluid samples. Once effective pretreatment methods are developed that remove abundant proteins selectively, one can delve more deeply into the proteome to see the more dilute species which may be disease biomarkers. This has the potential to increase substantially the quality of proteomics data upon biomarker discovery data rely. In turn, this will help to speed new pharmaceuticals to the market, target proper clinical populations, and help to monitor disease progression. These all may have a profound effect on personalized medicine and public health.