Limits...
Integrating multiple 'omics' analyses identifies serological protein biomarkers for preeclampsia.

Liu LY, Yang T, Ji J, Wen Q, Morgan AA, Jin B, Chen G, Lyell DJ, Stevenson DK, Ling XB, Butte AJ - BMC Med (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.

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.

Show MeSH

Related in: MedlinePlus

Study outline of the multi-’omics’-based discovery and validation of PE biomarkers. Candidate analytes, which failed subsequent validation, are greyed out. PE, preeclampsia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4226208&req=5

Figure 1: Study outline of the multi-’omics’-based discovery and validation of PE biomarkers. Candidate analytes, which failed subsequent validation, are greyed out. PE, preeclampsia.

Mentions: The overall sample allocation, PE biomarker discovery, validation and diagnostic panel construction steps are illustrated in Figure 1. Our study was conducted in two phases: (1) the discovery phase, which included both the in silico expression analysis (n = 111 PE and n = 152 control placenta samples) and the proteomics two-dimensional gel profiling (pooled n = 5 PE and pooled n = 5 control serum proteomes); and (2) the validation phase, which comprised the analysis of independent PE (n = 32) and control (n = 32) cohorts. All the serum samples were purchased from ProMedDX Inc. All serum samples were collected after informed consent was obtained and included detailed case report forms. Excluded from this study were patients who were current smokers, had a history of substance abuse, used in vitro fertilization assistance, had chronic hypertension and pregnancies complicated by intrauterine growth restriction. Case (PE) and control (normal pregnant) cohorts were matched for gestational age, ethnicity and parity.


Integrating multiple 'omics' analyses identifies serological protein biomarkers for preeclampsia.

Liu LY, Yang T, Ji J, Wen Q, Morgan AA, Jin B, Chen G, Lyell DJ, Stevenson DK, Ling XB, Butte AJ - BMC Med (2013)

Study outline of the multi-’omics’-based discovery and validation of PE biomarkers. Candidate analytes, which failed subsequent validation, are greyed out. PE, preeclampsia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4226208&req=5

Figure 1: Study outline of the multi-’omics’-based discovery and validation of PE biomarkers. Candidate analytes, which failed subsequent validation, are greyed out. PE, preeclampsia.
Mentions: The overall sample allocation, PE biomarker discovery, validation and diagnostic panel construction steps are illustrated in Figure 1. Our study was conducted in two phases: (1) the discovery phase, which included both the in silico expression analysis (n = 111 PE and n = 152 control placenta samples) and the proteomics two-dimensional gel profiling (pooled n = 5 PE and pooled n = 5 control serum proteomes); and (2) the validation phase, which comprised the analysis of independent PE (n = 32) and control (n = 32) cohorts. All the serum samples were purchased from ProMedDX Inc. All serum samples were collected after informed consent was obtained and included detailed case report forms. Excluded from this study were patients who were current smokers, had a history of substance abuse, used in vitro fertilization assistance, had chronic hypertension and pregnancies complicated by intrauterine growth restriction. Case (PE) and control (normal pregnant) cohorts were matched for gestational age, ethnicity and parity.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.

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.

Show MeSH
Related in: MedlinePlus