Vitaly O. Kheyfets, Andrew J. Sweatt, Mardi Gomberg-Maitland, D. Dunbar Ivy, Robin Condliffe, David G. Kiely, Allan Lawrie, Bradley A. Maron, Roham T. Zamanian, Kurt R. Stenmark
University of Colorado. Stanford University. George Washington University. University of Sheffield. Harvard University.
United States and United Kingdom
Canadian Respiratory Journal Open Research
CRJ Open Res 2023; 9:
DOI: 10.1183/23120541.00484-2022
Abstract
Background: Pulmonary arterial hypertension (PAH) is a heterogeneous and complex pulmonary vascular disease associated with substantial morbidity. Machine-learning algorithms (used in many PAH risk calculators) can combine established parameters with thousands of circulating biomarkers to optimise PAH prognostication, but these approaches do not offer the clinician insight into what parameters drove the prognosis. The approach proposed in this study diverges from other contemporary phenotyping methods by identifying patient-specific parameters driving clinical risk.
Methods: We trained a random forest algorithm to predict 4-year survival risk in a cohort of 167 adult PAH patients evaluated at Stanford University, with 20% withheld for (internal) validation. Another cohort of 38 patients from Sheffield University were used as a secondary (external) validation. Shapley values, borrowed from game theory, were computed to rank the input parameters based on their importance to the predicted risk score for the entire trained random forest model (global importance) and for an individual patient (local importance).
Results: Between the internal and external validation cohorts, the random forest model predicted 4-year risk of death/transplant with sensitivity and specificity of 71.0-100% and 81.0-89.0%, respectively. The model reinforced the importance of established prognostic markers, but also identified novel inflammatory biomarkers that predict risk in some PAH patients.
Conclusion: These results stress the need for advancing individualised phenotyping strategies that integrate clinical and biochemical data with outcome. The computational platform presented in this study offers a critical step towards personalised medicine in which a clinician can interpret an algorithm’s assessment of an individual patient.
Category
Diagnostic Testing for Pulmonary Vascular Disease. Risk Stratification
Potential Biomarkers Associated with Pulmonary Vascular Disease
Age Focus: Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes