Angiopoietin-1, angiopoietin-2 and bicarbonate as diagnostic biomarkers in children with severe sepsis

PLoS One. 2014 Sep 25;9(9):e108461. doi: 10.1371/journal.pone.0108461. eCollection 2014.

Abstract

Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasma samples provided by a tertiary care center's Pediatric Intensive Care Unit (PICU) from a group of 45 patients with varying sepsis severity at the time of admission. Canonical Correlation Analysis with the Forward Selection and Random Forests methods identified a particular set of biomarkers that included Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), and Bicarbonate (HCO[Formula: see text]) as having the strongest correlations with sepsis severity. The robustness and effectiveness of these biomarkers for classifying sepsis severity were validated by constructing a linear Support Vector Machine diagnostic classifier. We also show that the concentrations of Ang-1, Ang-2, and HCO[Formula: see text] enable predictions of the time dependence of sepsis severity in children.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Angiopoietin-1 / blood*
  • Angiopoietin-2 / blood*
  • Bicarbonates / blood*
  • Biomarkers / blood
  • Cluster Analysis
  • Humans
  • Intensive Care Units, Pediatric
  • Prognosis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sepsis / blood*
  • Sepsis / diagnosis*
  • Severity of Illness Index
  • Support Vector Machine

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Bicarbonates
  • Biomarkers

Grants and funding

This work was partially supported by DARPA (Space and Naval Warfare System Center Pacic) under award number N66001-11-1-4184 (http://www.darpa.mil/). Additional support for this work was provided by Infectious Disease Supercluster, Colorado State University, 2012 seed grant (http://infectiousdisease.colostate.edu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.