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

• Published in: Biochimica et biophysica acta Vol. 1860; no. 5; pp. 981 - 989
• Main Authors: Garbett, Nichola C., Brock, Guy N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: Algorithms; Blood Proteins - chemistry; Calorimetry, Differential Scanning; Case-Control Studies; data collection; Diagnostic classification; Differential scanning calorimetry; Humans; Logistic Models; lupus erythematosus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - diagnosis; patients; Penalized classification methods; Plasma proteome; Principal Component Analysis; proteome; Proteome - chemistry; Registries; Systemic lupus erythematosus; thermal stability; Thermodynamics; Thermogram; LR; LDA; GLM; SVM-SCAD; SVM; SLE; AUC; Systemic lupus erythematosus; DSC; SCAD; PLS; LASSO; LFRR; Penalized classification methods; TFM; LR-ENET; Cpex; Differential scanning calorimetry; LR-LASSO; ROC; SVM-ESCAD; PLS-DA; Thermogram; PC; Tmax; SPLS-DA; Diagnostic classification; Plasma proteome; LDA-LASSO
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2015.10.004

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. 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). 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. 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. 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. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah. •New approaches for the diagnostic analysis of thermograms were evaluated.•Classification performance was assessed using a large dataset of lupus and controls.•Thermogram feature metrics and principal components performed modestly.•Classification performance was higher for modern classification algorithms.•Uncovering biological drivers of thermogram changes can enhance diagnostic analysis.