A computational method to differentiate normal individuals, osteoarthritis and rheumatoid arthritis patients using serum biomarkers

• Published in: Journal of the Royal Society interface Vol. 11; no. 97; p. 20140428
• Main Authors: Heard, Bryan J., Rosvold, Joshua M., Fritzler, Marvin J., El-Gabalawy, Hani, Wiley, J. Preston, Krawetz, Roman J.
• Format: Journal Article
• Language: English
• Published: England The Royal Society 06-08-2014
• Subjects: Adult; Algorithms; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Artificial Neural Network; Biomarkers - blood; Cytokines; Cytokines - blood; Diagnosis, Computer-Assisted - methods; Diagnostic; Female; Humans; Machine Learning; Male; Middle Aged; Neural Networks (Computer); Osteoarthritis; Osteoarthritis - blood; Osteoarthritis - diagnosis; Pattern Recognition, Automated - methods; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Serum; artificial neural network; cytokines; diagnostic; machine learning; serum; osteoarthritis
• ISSN: 1742-5689; 1742-5662
• DOI: 10.1098/rsif.2014.0428

The objective of this study was to develop a method for categorizing normal individuals (normal, n = 100) as well as patients with osteoarthritis (OA, n = 100), and rheumatoid arthritis (RA, n = 100) based on a panel of inflammatory cytokines expressed in serum samples. Two panels of inflammatory proteins were used as training sets in the construction of two separate artificial neural networks (ANNs). The first training set consisted of all proteins (38 in total) and the second consisted of only the significantly different proteins expressed (12 in total) between at least two patient groups. Both ANNs obtained high levels of sensitivity and specificity, with the first and second ANN each diagnosing 100% of test set patients correctly. These results were then verified by re-investigating the entire dataset using a decision tree algorithm. We show that ANNs can be used for the accurate differentiation between serum samples of patients with OA, a diagnosed RA patient comparator cohort and normal/control cohort. Using neural network and systems biology approaches to manage large datasets derived from high-throughput proteomics should be further explored and considered for diagnosing diseases with complex pathologies.