Differential scanning calorimetry as a complementary diagnostic tool for the evaluation of biological samples

Biochim Biophys Acta. 2016 May;1860(5):981-989. doi: 10.1016/j.bbagen.2015.10.004. Epub 2015 Oct 14.

Abstract

Background: Differential scanning calorimetry (DSC) is a tool for measuring the thermal stability profiles of complex molecular interactions in biological fluids. DSC profiles (thermograms) of biofluids provide specific signatures which are being utilized as a new diagnostic approach for characterizing disease but the development of these approaches is still in its infancy.

Methods: This article evaluates several approaches for the analysis of thermograms which could increase the utility of DSC for clinical application. Thermograms were analyzed using localized thermogram features and principal components (PCs). The performance of these methods was evaluated alongside six models for the classification of a data set comprised of 300 systemic lupus erythematosus (SLE) patients and 300 control subjects obtained from the Lupus Family Registry and Repository (LFRR).

Results: Classification performance was substantially higher using the penalized algorithms relative to localized features/PCs alone. The models were grouped into two sets, the first having smoother solution vectors but lower classification accuracies than the second with seemingly noisier solution vectors.

Conclusions: Coupling thermogram technology with modern classification algorithms provides a powerful diagnostic approach for analysis of biological samples. The solution vectors from the models may reflect important information from the thermogram profiles for discriminating between clinical groups.

General significance: DSC thermograms show sensitivity to changes in the bulk plasma proteome that correlate with clinical status. To move this technology towards clinical application the development of new approaches is needed to extract discriminatory parameters from DSC profiles for the comparison and diagnostic classification of patients.

Keywords: Diagnostic classification; Differential scanning calorimetry; Penalized classification methods; Plasma proteome; Systemic lupus erythematosus; Thermogram.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Blood Proteins / chemistry*
  • Calorimetry, Differential Scanning
  • Case-Control Studies
  • Humans
  • Logistic Models
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / diagnosis
  • Principal Component Analysis
  • Proteome / chemistry*
  • Registries*
  • Thermodynamics

Substances

  • Blood Proteins
  • Proteome