Unsupervised Cluster Analysis Reveals Distinct Subtypes of ME/CFS Patients Based on Peak Oxygen Consumption and SF-36 Scores

Abstract

Biomarker; Cardiopulmonary exercise test; Chronic fatigue syndrome

Biomarcador; Prova d'esforç cardiopulmonar; Síndrome de fatiga crònica

Biomarcador; Prueba de esfuerzo cardiopulmonar; Síndrome de fatiga crónica

Purpose Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET). Methods Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber's classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters. Findings The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p − value < 0.05) for classifying patients with ME/CFS. Implications Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.