Proteomic analysis of amniotic fluid to identify women with preterm labor and intra-amniotic inflammation/infection: The use of a novel computational method to analyze mass spectrometric profiling
- 1 January 2008
- journal article
- research article
- Published by Informa UK Limited in The Journal of Maternal-Fetal & Neonatal Medicine
- Vol. 21 (6), 367-387
- https://doi.org/10.1080/14767050802045848
Abstract
Objective. Examination of the amniotic fluid proteome has been used to identify biomarkers for intra-amniotic inflammation as well as those that may be useful in predicting the outcome of preterm labor. The purpose of this study was to combine a novel computational method of pattern discovery with mass spectrometric proteomic profiling of amniotic fluid to discover biomarkers of intra-amniotic infection/inflammation (IAI). Methods. This cross-sectional study included patients with spontaneous preterm labor and intact membranes who delivered at term (n = 59) and those who delivered preterm with IAI (n = 60). Proteomic profiling was performed using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. A proteomic profile was acquired through multiple simultaneous SELDI conditions, which were combined in a single proteomic ‘fingerprint’ using a novel computational approach. Classification of patients based on their associated surface-enhanced laser desorption/ionization–time of flight (SELDI–TOF) mass spectra as belonging to either the class of individuals with preterm delivery with IAI or term delivery was accomplished by constructing an empirical model. The first phase in the construction of this empirical model involved the selection of adjustable parameters utilizing a training/testing subset of data. The second phase tested the generalization of the model by utilizing a blinded validation set of patients who were not employed in parameter selection. Results. Gestational age at amniocentesis was not significantly different between the groups. Thirty-nine unique mass spectrometric peaks discriminated patients with preterm labor/delivery with IAI from those with preterm labor and term delivery. In the testing/training dataset, the classification accuracies (averaged over 100 random draws) were: 91.4% (40.2/44) for patients with preterm delivery with IAI, and 91.2% (40.1/44) for term delivery. The overall accuracy of the classification of patients in the validation dataset was 90.3% (28/31). Conclusions. Proteomic analysis of amniotic fluid allowed the identification of mass spectrometry features, which can distinguish patients with preterm labor with IAI from those with preterm labor without inflammation or infection who subsequently delivered at term.Keywords
This publication has 100 references indexed in Scilit:
- Metabolomics in premature labor: a novel approach to identify patients at risk for preterm deliveryThe Journal of Maternal-Fetal & Neonatal Medicine, 2010
- Human spontaneous labor without histologic chorioamnionitis is characterized by an acute inflammation gene expression signatureAmerican Journal of Obstetrics and Gynecology, 2006
- Analysis of microarray experiments of gene expression profilingAmerican Journal of Obstetrics and Gynecology, 2006
- Insights into the Physiology of Childbirth Using TranscriptomicsPLoS Medicine, 2006
- Labor-Associated Gene Expression in the Human Uterine Fundus, Lower Segment, and CervixPLoS Medicine, 2006
- Inflammatory Aetiology of Human Myometrial Activation Tested Using Directed GraphsPLoS Computational Biology, 2005
- Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranesAmerican Journal of Obstetrics and Gynecology, 2004
- A Gene-Expression Signature as a Predictor of Survival in Breast CancerNew England Journal of Medicine, 2002
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000
- Amniotic Fluid Interleukin‐6 Determinations Are of Diagnostic and Prognostic Value in Preterm LaborAmerican Journal of Reproductive Immunology, 1993