title: Biomarker interactions are better predictors of spontaneous preterm birth.
abstract: OBJECTIVE
  The objective of this study was to assess the role of biomarker interactions as predictors of spontaneous preterm birth (PTB) using multifactor dimensionality reduction (MDR) analysis. With MDR, a nonparametric, unsupervised, model-free approach, we tested for biomarker interactions within maternal-fetal compartments in 2 racial groups: African Americans (AA) and Caucasians (C).
  
  
  METHODS
  A total of 36 biomarkers from maternal plasma (MP), cord plasma (CP), and amniotic fluid (AF) were analyzed from 191 patients. The MDR combined attribute selection, construction, and classification to detect biomarker interactions that were assessed for generality and significance using 10× cross-validation and permutation testing. Selected significant interactive models were replicated with additional samples.
  
  
  RESULTS
  The interactive model containing interleukin (IL)-2, angiopoietin 2 (ANGPT-2), and IL-6 receptor was significant in AA MP. In AA CP, the IL-8 and tumor necrosis factor (TNF) receptor 1 model was significant. In AA AF, the ANGPT-2 and macrophage inflammatory protein 1 alpha model was significant. Replication of the AA MP model using 54 additional AA MP samples confirmed predictability of these biomarkers. In C AF, interaction was observed between ANGPT-2, monocyte chemotactic protein 3, and TNF-α, but no other interactions were significant in C.
  
  
  CONCLUSIONS
  Using MDR, we identified biomarker interactions that are predictors of PTB even in the absence of a main effect with a single biomarker.
authors.affiliation: 1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine Perinatal Research, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bhat
authors.forename: S M
authors.initials: SM
authors.lastname: Williams
authors.forename: G R
authors.initials: GR
authors.lastname: Saade
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000208:ethnology; D000650:Amnion / Q000378:metabolism; D042702:Angiopoietin-2 / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D011237:Predictive Value of Tests; D011247:Pregnancy; D047928:Premature Birth / Q000175:diagnosis* / Q000208:ethnology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D044465:White People / Q000208:ethnology; D055815:Young Adult
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha
keywords: biomarker; mdr; preterm