Diagnostic proteomic profiles for aneuploidy

描述(由申请人提供)：安全和准确地诊断染色体异常是产前筛查的主要目标。目前对21三体(唐氏综合征；DS)等非整倍体的评估包括提示性血清检测，这些检测随后通过羊膜穿刺术或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这一假设，即DS的母体血清标志物存在，并可用于设计准确的非侵入性测试。在我们的SBIR阶段-L研究中，我们确定了母亲血清中特定的差异表达蛋白质生物标记物，这些生物标记物是DS妊娠的一贯特征。在这个第二阶段的应用中，我们建议(1)验证假设的DS生物标记物集在来自较快的NIH试验数据库的DS和胎龄和性别匹配的对照样本的更大队列中的差异表达，以及(2)开发基于MALDI的原型高通量分析，该原型将在使用较快的数据集和ProeoGenix，Inc.银行的额外DS和对照样本的盲目研究中得到验证。拟议的研究扩展了我们最初的生物发现研究，并构成了实施基于蛋白质组学的分析测试的合乎逻辑的下一步，该测试可以商业提供，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.