Diagnostic proteomic profiles for aneuploidy

描述（由申请人提供）：安全准确地诊断染色体异常是产前筛查的主要目标。非整倍体如21三体（唐氏综合征; DS）的评估目前涉及提示性血清试验，随后通过侵入性程序如穿刺或绒毛膜绒毛取样进行验证。我们已经应用蛋白质组学分析的工具，以确认这一假设，即母体血清标记物的DS存在，并可用于设计准确的和非侵入性的测试。在我们的SBIR I期研究中，我们鉴定了母体血清中特异性差异表达的蛋白质生物标志物，这些蛋白质生物标志物始终是DS妊娠的特征。在该II期申请中，我们建议（1）在来自FASTER NIH试验数据库的较大DS和胎龄和性别匹配对照样本队列中验证推定DS生物标志物集的差异表达，（2）开发一个基于MALDI的高性能原型系统。将在盲态研究中采用FASTER数据集（补充额外的DS和对照样品）验证的通量试验，ProeoGenix公司拟议的研究扩展了我们最初的生物发现研究，并构成了实施基于蛋白质组学的分析测试的合理下一步，该测试可以在商业上提供，并将取代目前的测试模式。

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.