Integrating Multiple 'omics' Analyses Identifies Serological Protein Biomarkers for Preeclampsia

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2013 Nov 8

PMID 24195779

Citations 24

Authors

Linda Y Liu

Ting Yang

Jun Ji

Qiaojun Wen

Alexander A Morgan

Bo Jin

Gongxing Chen

Deirdre J Lyell

David K Stevenson

Xuefeng B Ling

Atul J Butte

Affiliations

Soon will be listed here.

Abstract

Background: Preeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-'omics' based discovery approach.

Methods: Seven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment.

Results: In addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively.

Conclusions: Both early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE.

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