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Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.

Buhimschi IA, Zhao G, Rosenberg VA, Abdel-Razeq S, Thung S, Buhimschi CS - PLoS ONE (2008)

Bottom Line: 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.The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, United States of America. irina.buhimschi@yale.edu

ABSTRACT

Background: 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.

Methodology/principal findings: 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.

Conclusion/significance: 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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Distribution of amniotic SELDI tracings based on proteomic patterns.
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pone-0002049-g003: Distribution of amniotic SELDI tracings based on proteomic patterns.

Mentions: Based on the established proteomic fingerprints of inflammation and bleeding, we identified that of the 285 SELDI tracings screened, 92 (32%) had either evidence of intra-amniotic inflammation (n = 71, MR 3-4), bleeding (n = 6, Hb peaks present) or both (n = 15) (Figure 3). Application of the hierarchical algorithm to the hypervariable areas of the remaining 193 tracings (no inflammation and no bleeding patterns) identified a novel discriminatory profile consisting of 5 proteomic peaks in the 10–12.5 kDa area of interest (Q-profile) (Figure 2A) in 32 patients. In addition, peaks corresponding to those of the Q-profile were found in 7 cases that also had inflammation and in one case where bleeding coexisted with inflammation. The masses of the biomarkers components of the Q-profile are listed in Figure 2B.


Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.

Buhimschi IA, Zhao G, Rosenberg VA, Abdel-Razeq S, Thung S, Buhimschi CS - PLoS ONE (2008)

Distribution of amniotic SELDI tracings based on proteomic patterns.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2315798&req=5

pone-0002049-g003: Distribution of amniotic SELDI tracings based on proteomic patterns.
Mentions: Based on the established proteomic fingerprints of inflammation and bleeding, we identified that of the 285 SELDI tracings screened, 92 (32%) had either evidence of intra-amniotic inflammation (n = 71, MR 3-4), bleeding (n = 6, Hb peaks present) or both (n = 15) (Figure 3). Application of the hierarchical algorithm to the hypervariable areas of the remaining 193 tracings (no inflammation and no bleeding patterns) identified a novel discriminatory profile consisting of 5 proteomic peaks in the 10–12.5 kDa area of interest (Q-profile) (Figure 2A) in 32 patients. In addition, peaks corresponding to those of the Q-profile were found in 7 cases that also had inflammation and in one case where bleeding coexisted with inflammation. The masses of the biomarkers components of the Q-profile are listed in Figure 2B.

Bottom Line: 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.The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, United States of America. irina.buhimschi@yale.edu

ABSTRACT

Background: 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.

Methodology/principal findings: 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.

Conclusion/significance: 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.

Show MeSH
Related in: MedlinePlus