title: Integrating multiple 'omics' analyses identifies serological protein biomarkers for preeclampsia.
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.
authors.forename: Linda Y
authors.initials: LY
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Wen
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Morgan
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Gongxing
authors.initials: G
authors.lastname: Chen
authors.forename: Deirdre J
authors.initials: DJ
authors.lastname: Lyell
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
authors.affiliation: Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.
authors.forename: Xuefeng B
authors.initials: XB
authors.lastname: Ling
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000503:physiopathology*; D011247:Pregnancy; D012698:Serologic Tests / Q000379:methods; D044967:Serum / Q000737:chemistry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins