Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.
Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.
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DOI：
10.1371/journal.pone.0002049
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发表时间：
2008-04-23
期刊：
影响因子：
3.7
通讯作者：
Buhimschi, Catalin S.
中科院分区：
文献类型：
--
作者：
Buhimschi, Irina A.;Zhao, Guomao;Rosenberg, Victor A.;Abdel-Razeq, Sonya;Thung, Stephen;Buhimschi, Catalin S.
尽管蛋白质组学的最新进展为导致早产的几种不同发病机制（炎症、出血）提供了一个新的视角，但大多数早产的病因仍然难以捉摸。我们对羊水进行了多维蛋白质组学分析，以确定在没有炎症或出血的情况下与早产相关的途径。使用表面增强激光解吸电离飞行时间（SELDI-TOF）质谱法从新鲜羊水中产生蛋白质组指纹，共286个连续样本，这些样本来自出现早产或早产胎膜早破体征或症状的妇女。在32%（92/286）的SELDI追踪中检测到炎症和/或出血蛋白质组模式。在剩余的追踪中，基于量化蛋白质组指纹之间的相似性/不相似性的描述符应用分层算法。这允许基于在10-12.5 kDa质量区域中存在5个SELDI峰来鉴定新谱（Q-谱）。显示Q曲线的妇女（平均值±SD，胎龄：25±4周，n = 40）更有可能早产，尽管在完整的胎膜和正常羊水临床结果的背景下进行了期待治疗。 利用鉴定为中心的蛋白质组学技术（荧光二维差异凝胶电泳，机器人胰蛋白酶消化和质谱）结合蛋白质分析通过进化关系（PANTHER）本体分类，我们确定，在羊水中的差异表达的蛋白质主要参与非炎症生物过程，如蛋白质代谢，信号转导和运输。羊水的蛋白质组分析结合非分级生物信息学算法确定了一个亚组的患者在没有羊膜内炎症或出血的情况下有早产风险，这表明一种新的导致早产的发病途径。改变的蛋白质可能为治疗干预和未来药物开发提供机会，以预防早产。
Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding. A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10–12.5 kDa mass area. Women displaying the Q-profile (mean±SD, gestational age: 25±4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport. Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity.
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DOI：
10.1111/j.1471-0528.2004.00340.x
发表时间：
2005-02-01
影响因子：
5.8
作者：
Buhimschi, IA;Christner, R;Buhimschi, CS
通讯作者：
Buhimschi, CS
DOI：
10.1016/0002-9378(95)90189-2
发表时间：
1995-07-01
影响因子：
9.8
作者：
KANAYAMA, N;ELMARADNY, E;TERAO, T
通讯作者：
TERAO, T
DOI：
10.1016/0028-2243(95)02087-9
发表时间：
1995-06-01
影响因子：
2.6
作者：
KANAYAMA, N;ELMARADNY, E;TERAO, T
通讯作者：
TERAO, T
影响因子：
4.4
作者：
Michaels, John-Edward A.;Dasari, Surendra;Nagalla, Srinivasa R.
通讯作者：
Nagalla, Srinivasa R.
影响因子：
7.8
作者：
Chakravarti, S;Magnuson, T;Lass, JH;Jepsen, KJ;LaMantia, C;Carroll, H
通讯作者：
Carroll, H