An improved clinical and genetics-based prediction model for diabetic foot ulcer healing

The goal of this investigation was to use comprehensive prediction modeling tools and available genetic information to try to improve upon the performance of simple clinical models in predicting whether a diabetic foot ulcer (DFU) will heal.We utilized a cohort study (n=206) that included clinical factors, measurements of circulating endothelial precursor cells (CEPC), and fine sequencing of the NOS1AP gene. We derived and selected relevant predictive features from this patient-level information using statistical and machine learning techniques. We then developed prognostic models using machine learning approaches and assessed predictive performance. The presentation is consistent with TRIPOD requirements.Models using baseline clinical and CEPC data had an area under the receiver operating characteristic curve (AUC) of 0.73 (0.66, 0.80). Models using only single nucleotide polymorphisms (SNPs) of the NOS1AP gene had an AUC of 0.67 (95% CI: (0.59, 0.75)). However, models incorporating baseline and SNP information resulted in improved AUC (0.80, 95% CI (0.73, 0.87)).We provide a rigorous analysis demonstrating the predictive potential of genetic information in DFU healing. In this process, we present a framework for using advanced statistical and bioinformatics techniques for creating superior prognostic models and identify potentially predictive SNPs for future research.We have developed a new benchmark for which future predictive models can be compared against. Such models will enable wound care experts to more accurately predict whether a patient will heal and aid clinical trialists in designing studies to evaluate therapies for subjects likely or unlikely to heal.