Diagnostic proteomic profiles for aneuploidy

描述（申请人提供）：安全准确地诊断染色体异常是产前筛查的主要目标。非整倍体的评估，如21三体（唐氏综合征；DS），目前包括暗示性血清测试，随后通过羊膜穿刺术或绒毛膜绒毛取样等侵入性程序进行验证。我们应用蛋白质组学分析的工具来证实孕妇血清DS标记物存在的假设，并可用于设计准确和无创的检测方法。在我们的SBIR一期研究中，我们在母体血清中发现了特异性差异表达蛋白生物标志物，这些生物标志物与DS妊娠的特征一致。在这个ii期申请中，我们建议(1)在来自FASTER NIH Trial数据库的更大的DS、胎龄和性别匹配的对照样本中验证假定的DS生物标志物集的差异表达，(2)开发一个基于maldi的原型高通量分析，将在使用FASTER数据集补充ProeoGenix， Inc.的额外DS和对照样本的盲法研究中进行验证。拟议的研究扩展了我们最初的生物发现研究，并构成了实现基于蛋白质组学的分析测试的逻辑下一步，可以提供商业服务，并将取代当前的测试模式。

DESCRIPTION (provided by applicant): Safe and accurate diagnosis of chromosomal abnormalities is a major goal of prenatal screening. The assessment of aneuploidies such as trisomy 21 (Down's syndrome; DS) currently involves suggestive serum tests that are subsequently validated by invasive procedures such as amniocentesis or chorionic villus sampling. We have applied the tools of proteomic analysis to confirm the hypothesis that maternal serum markers for DS exist and can be used in the design of accurate and non-invasive tests. In our SBIR Phase-l studies, we identified specific differentially expressed protein biomarkers in maternal serum that were consistently characteristic of DS pregnancies. In this Phase-ll application, we propose to (1) verify the differential expression of the putative DS biomarker set in a larger cohort of DS and gestational age and sex-matched control samples derived from the FASTER NIH Trial database, and (2) develop a prototype MALDI-based high-throughput assay that will be validated in a blinded study employing the FASTER dataset supplemented with additional DS and control samples banked by ProeoGenix, Inc. The proposed studies extend our initial biodiscovery research and constitute the logical next step in the implementation of a proteomics-based analytical test that can be offered commercially, and which will replace current testing modalities.