Open Access Research article

Integrating multiple ‘omics’ analyses identifies serological protein biomarkers for preeclampsia

Linda Y Liu1, Ting Yang2, Jun Ji2, Qiaojun Wen2, Alexander A Morgan2, Bo Jin2, Gongxing Chen2, Deirdre J Lyell3, David K Stevenson1, Xuefeng B Ling2* and Atul J Butte1*

Author Affiliations

1 Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA

2 Department of Surgery, Stanford University, Stanford, CA 94305, USA

3 Department of Obstetrics & Gynecology, Stanford University, 269 Campus Drive, CCSR 4245A, Stanford, CA 94305, USA

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BMC Medicine 2013, 11:236  doi:10.1186/1741-7015-11-236

Published: 6 November 2013



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.


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.


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.


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.

2D gel (two-dimensional gel electrophoresis); LCMS; Multiplex analysis; Preeclampsia; Proteomic profile