Early identification of high-risk individuals for mortality after lung transplantation: A retrospective cohort study with topological feature engineering.

Lung transplantation remains the only definitive treatment for end-stage respiratory failure; however, it has substantial post-operative mortality risk. Current methods like the Lung Transplant Risk Index offer limited predictive performance. This study introduces a novel topological feature engineering model to assess mortality risk. The objective is to improve predictive accuracy by capturing complex temporal patterns while ensuring interpretability. A retrospective cohort study was conducted using clinical data from lung transplant recipients. The model integrates static and time-dependent variables through topological feature extraction, enabling sequential risk updating at transplantation, ICU admission, and throughout early post-operative course. Performance was compared to established methods using a held-out test set. Metrics included accuracy, sensitivity, specificity, and AUC. Interpretability was assessed using Shapley Additive explanations. The proposed model demonstrated superior predictive performance compared to traditional clinical risk scores (LTRI, CCI) and standard machine learning models. On the test dataset, it achieved 87.4% accuracy, 84.1% sensitivity, and 89.6% specificity, with an absolute AUC gain of 0.08 over the best non-topological baseline (p < 0.001). The model consistently outperformed existing approaches across subgroups including age, underlying disease, and transplant type. Shapley analysis revealed that dynamic variables such as early post-operative oxygenation trends, immunosuppressive load, and inflammatory markers were among the most critical contributors to mortality risk. The integration of topological features significantly enhances prediction of post-transplant mortality risk. These findings highlight topological transformers as a valuable tool for precision medicine and clinical decision support.