Mining Complex Human Fluids for New Potential Protein Biomarkers

挖掘复杂的人体液体以寻找新的潜在蛋白质生物标志物

基本信息

批准号：
9049033
负责人：
Frank Jahnke
金额：
$ 30万
依托单位：
SONATA BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-23 至 2018-09-22
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9049033
关键词：
Adsorption Affect Affinity Albumins Antibodies Attention Beds Binding Biological Markers Buffers Cells Chromatography Clinic Complement Complex DNA Data Development Diagnostic Diagnostic tests Disease Elements Excision Goals Human Libraries Liquid Chromatography Liquid substance MYO5A gene Malignant Neoplasms Malignant neoplasm of lung Marketing Methods Mining Nucleic Acids Organism Performance Pharmacologic Substance Phase Plasma Polymethyl Methacrylate Process Protein Dynamics Protein Isoforms Proteins Proteome Proteomics Research Sampling Serum Serum Albumin Solid Solutions Source Specificity Testing Time Tissues Two-Dimensional Gel Electrophoresis Work aptamer cohort combinatorial cost effective dimer disulfide bond expectation gel electrophoresis interest product development protein complex protein protein interaction public health relevance surfactant tandem mass spectrometry tool

项目摘要

DESCRIPTION (provided by applicant): In this proposal we seek to demonstrate a new experimental approach to develop a new subtractive method to remove abundant proteins from complex human fluid samples. The ultimate goal is to develop a suite of methods or tools to facilitate the de novo discovery of a complete set of low-abundance potential protein biomarkers from which more targeted studies can be performed. A particular interest is in the discovery of potential biomarkers for cancers, and in the past we have studied lung cancer samples and references drawn from the same cohort. In this Phase I proposal, we seek to demonstrate the selective and specific removal of human serum albumin isoforms and dimers from human plasma. These serum albumins comprise half of the protein in human serum or plasma, and cause very real issues with both tandem mass spectrometry and difference gel electrophoresis approaches. The Phase II would extend to work to remove three orders of magnitude of abundant proteins, a 50 times increase from existing state-of-the-art methods. One key feature is that the conditions are chosen to minimize protein-protein interactions, which compromise the performance of existing methods. The simplified human fluid samples produced will be compatible with both 2D gel electrophoresis and liquid chromatography- tandem mass spectrometry approaches.

描述（由申请人提供）：在本提案中，我们试图展示一种新的实验方法，以开发一种新的消减方法，以去除复杂的人体液体样本中丰富的蛋白质。最终目标是开发一套方法或工具来促进去除。新发现了一整套低丰度的潜在蛋白质生物标志物，从中可以进行更有针对性的研究，特别感兴趣的是发现癌症的潜在生物标志物，在过去，我们研究了癌症肺部样本和来自癌症肺样本的参考文献。同一队列中。在这一第一阶段的提案中，我们试图证明从人血浆中选择性和特异性去除人血清白蛋白异构体和二聚体。这些血清白蛋白占人血清或血浆中蛋白质的一半，并导致串联质谱和二聚体产生非常现实的问题。第二阶段将扩展到去除三个数量级的丰富蛋白质，比现有最先进的方法增加了 50 倍。蛋白质相互作用，这会损害所产生的简化人体液体样品将与二维凝胶电泳和液相色谱-串联质谱方法兼容。