Algorithm development for diagnostic biomarker assays

Int Rev Neurobiol. 2011:101:279-98. doi: 10.1016/B978-0-12-387718-5.00011-0.

Abstract

This chapter describes the ground-breaking development of a serum-based test to help confirm the diagnosis of schizophrenia. A multiplex panel of 51 immunoassays was developed that allowed reproducible identification of schizophrenia patients compared to controls with high sensitivity and specificity. Validation of this test consisted of developing a linear support vector machine decision rule and testing its performance using cross-validation. This resulted in readjustment of the panel and algorithm to a smaller set of 40 robust assays, along with a simple procedure for maintenance and recalibration across future measurement changes associated with different reagent lots. The resulting decision rule delivered a sensitive and specific prediction for presence of schizophrenia in subjects compared to matched controls, with a receiver operating characteristic area under the curve of 88%. Performance of the recalibrated decision rule remained constant across lot changes, ensuring consistency and accuracy.

Publication types

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

MeSH terms

  • Algorithms*
  • Biomarkers / analysis*
  • Biomarkers / blood
  • Humans
  • Immunoassay / methods*
  • Immunoassay / trends
  • Molecular Diagnostic Techniques / methods*
  • Molecular Diagnostic Techniques / trends
  • Predictive Value of Tests
  • Reproducibility of Results
  • Schizophrenia / blood
  • Schizophrenia / diagnosis*
  • Schizophrenia / physiopathology

Substances

  • Biomarkers