Predicting Preterm Birth Using Proteomics

Abstract

The complexity of preterm birth (PTB), both spontaneous and medically indicated, and its various etiologies and associated risk factors pose a significant challenge for developing tools to accurately predict risk. This review focuses on the discovery of proteomics signatures that might be useful for predicting spontaneous PTB or preeclampsia, which often results in PTB. We describe methods for proteomics analyses, proteomics biomarker candidates that have so far been identified, obstacles for discovering biomarkers that are sufficiently accurate for clinical use, and the derivation of composite signatures including clinical parameters to increase predictive power.

Keywords: Biomarkers; Biosignatures; Composite signatures; Computation; Multiomics; Omics; Preeclampsia; Proteome.

Fig. 1.. Predictive Modeling of Preterm Birth.

A. This receiver operating characteristic (ROC) curve analysis used each biological modality and the integrated approach. The mean area under the ROC curve and 95% confidence interval (CI) for each modality were as follows: transcriptomics (area under the ROC [AUROC]; 0.73; 95% CI: 0.61, 0.83), metabolomics (AUROC: 0.59; 95% CI: 0.47, 0.72), proteomics (AUROC: 0.75; 95% CI: 0.64, 0.85), and integrated (AUROC: 0.83; 95% CI: 0.72, 0.91). B. Circle size is proportional to −log10 (Wilcoxon) p-value for discrimination between term pregnancies and preterm births. Top features included an inflammatory module (which included interleukin 6 [IL-6]; IL-1 receptor antagonist [IL-1RA], a regulatory member of the IL-1 family whose expression is induced IL-1β under inflammatory conditions; granulocyte colony-stimulating factor [G-CSF]; retinoic acid receptor responder protein 2 [RARRES2]; chemokine ligand 3 [CCL3]; angiopoietin-like 4 [ANGPTL4]; protein-arginine deiminase type II [PADI2]; and transferrin receptor [TfR]) and a metabolomic module (which was enriched for glutamine and glutamate metabolism [Fisher test for pathway enrichment analysis p<4.4×10⁻⁹] and valine, leucine, and isoleucine biosynthesis pathways [p<7.3×10⁻⁶]). From Jehan F, Sazawal S, Baqui AH, et al. Multiomics characterization of preterm birth in low- and middle-income countries. JAMA Netw Open 2020;3(12):e2029655.