A warning machine learning algorithm for early knee osteoarthritis structural progressor patient screening

Abstract

Aim: In osteoarthritis (OA) there is a need for automated screening systems for early detection of structural progressors. We built a comprehensive machine learning (ML) model that bridges major OA risk factors and serum levels of adipokines/related inflammatory factors at baseline for early prediction of at-risk knee OA patient structural progressors over time. Methods: The patient- and gender-based model development used baseline serum levels of six adipokines, three related inflammatory factors and their ratios (36), as well as major OA risk factors [age and bone mass index (BMI)]. Subjects (677) were selected from the Osteoarthritis Initiative (OAI) progression subcohort. The probability values of being structural progressors (PVBSP) were generated using our previously published prediction model, including five baseline structural features of the knee, i.e. two X-rays and three magnetic resonance imaging variables. To identify the most important variables amongst the 47 studied in relation to PVBSP, we employed the ML feature classification methodology. Among five supervised ML algorithms, the support vector machine (SVM) demonstrated the best accuracy and use for gender-based classifiers development. Performance and sensitivity of the models were assessed. A reproducibility analysis was performed with clinical trial OA patients. Results: Feature selections revealed that the combination of age, BMI, and the ratios CRP/MCP-1 and leptin/CRP are the most important variables in predicting OA structural progressors in both genders. Classification accuracies for both genders in the testing stage (OAI) were >80%, with the highest sensitivity of CRP/MCP-1. Reproducibility analysis showed an accuracy ⩾92%; the ratio CRP/MCP-1 demonstrated the highest sensitivity in women and leptin/CRP in men. Conclusion: This is the first time that such a framework was built for predicting knee OA structural progressors. Using this automated ML patient- and gender-based model, early prediction of knee structural OA progression can be performed with high accuracy using only three baseline serum biomarkers and two risk factors. Plain language summary Machine learning model for early knee osteoarthritis structural progression Knee osteoarthritis is a well-known debilitating disease leading to reduced mobility and quality of life – the main causes of chronic invalidity. Disease evolution can be slow and span many years; however, for some individuals, the progression/evolution can be fast. Current treatments are only symptomatic and conventional diagnosis of osteoarthritis is not very effective in early identification of patients who will progress rapidly. To improve therapeutic approaches, we need a robust prediction model to stratify osteoarthritis patients at an early stage according to risk of joint structure disease progression. We hypothesize that a prediction model using a machine learning system would enable such an early identification of individuals for whom osteoarthritis knee structure will degrade rapidly. Data were from the Osteoarthritis Initiative, a National Institute of Health (United States) databank, and the robustness and generalizability of the developed model was further evaluated using osteoarthritis patients from an external cohort. Using the supervised machine learning system (support vector machine), we developed an automated patient- and gender-based model enabling an early clinical prognosis for individuals at high risk of structural progressive osteoarthritis. In brief, this model employed at baseline (when the subject sees a physician) easily obtained features consisting of the two main osteoarthritis risk factors, age and bone mass index (BMI), in addition to the serum levels of three molecules. Two of these molecules belong to a family of factors names adipokines and one to a related inflammatory factor. In brief, the model comprising a combination of age, BMI, and the ratios CRP/MCP-1 and leptin/CRP were found very robust for both genders, and the high accuracy persists when tested with an external cohort conferring the gender-based model generalizability. This study offers a new automated system for identifying early knee osteoarthritis structural progressors, which will significantly improve clinical prognosis with real time patient monitoring.

Mass spectrometry-based proteomics identify novel serum osteoarthritis biomarkers

“…Nonetheless, it is worth mentioning that a ratio of serum CRP with another molecule (monocyte chemoattractant protein-1 [MCP-1]) was suggested as an OA biomarker. This ratio has been found associated with OA symptoms and predicted, in combination with other factors, OA individuals with knee structural degenerative progression [ 37 , 71 ]. Furthermore, CRP is also known to activate the classical complement pathway by binding to C1q [ 72 ].…”

Soluble biological markers in osteoarthritis

“… 131 Finally, Martel-Pelletier investigators using an automated machine learning patient and sex-based model identified three baseline serum biomarkers [ratios CRP/monocyte chemoattractant protein-1 ratios CRP/-1 and leptin/MCP-1] and two clinical risk factors (age and BMI) as the most important variables for the prediction of strutural progression. 132 , 133 …”

Osteoarthritis endotype discovery via clustering of biochemical marker data

“…At present, defining the appropriate outcome measures that are needed for OA clinical trials and the objective assessment of new therapies is challenging 19. Therefore, new computational methods based on machine learning (ML) and big data analytics can help advance this field of research by enabling protocols for patient classification into subtypes, using a combination of clinical, biochemical and/or imaging data 20–22…”