An artificial intelligence framework for end-to-end rare disease phenotyping from clinical notes using large language models

Phenotyping is fundamental to rare disease diagnosis, but manual curation of structured phenotypes from clinical notes is labor-intensive and difficult to scale. Existing artificial intelligence approaches typically optimize individual components of phenotyping but do not operationalize the full clinical workflow of extracting features from clinical text, standardizing them to Human Phenotype Ontology (HPO) terms, and prioritizing diagnostically informative HPO terms. We developed RARE-PHENIX, an end-to-end AI framework for rare disease phenotyping that integrates large language model-based phenotype extraction, ontology-grounded standardization to HPO terms, and supervised ranking of diagnostically informative phenotypes. We trained RARE-PHENIX using data from 2,671 patients across 11 Undiagnosed Diseases Network clinical sites, and externally validated it on 16,357 real-world clinical notes from Vanderbilt University Medical Center. Using clinician-curated HPO terms as the gold standard, RARE-PHENIX consistently outperformed a state-of-the-art deep learning baseline (PhenoBERT) across ontology-based similarity and precision-recall-F1 metrics in end-to-end evaluation (i.e., ontology-based similarity of 0.70 vs. 0.58). Ablation analyses demonstrated performance improvements with the addition of each module in RARE-PHENIX (extraction, standardization, and prioritization), supporting the value of modeling the full clinical phenotyping workflow. By modeling phenotyping as a clinically aligned workflow rather than a single extraction task, RARE-PHENIX provides structured, ranked phenotypes that are more concordant with clinician curation and has the potential to support human-in-the-loop rare disease diagnosis in real-world settings.

Development of deep learning algorithms to categorize free-text notes pertaining to diabetes: convolution neural networks achieve higher accuracy than support vector machines

Health professionals can use natural language processing (NLP) technologies when reviewing electronic health records (EHR). Machine learning free-text classifiers can help them identify problems and make critical decisions. We aim to develop deep learning neural network algorithms that identify EHR progress notes pertaining to diabetes and validate the algorithms at two institutions. The data used are 2,000 EHR progress notes retrieved from patients with diabetes and all notes were annotated manually as diabetic or non-diabetic. Several deep learning classifiers were developed, and their performances were evaluated with the area under the ROC curve (AUC). The convolutional neural network (CNN) model with a separable convolution layer accurately identified diabetes-related notes in the Brigham and Womens Hospital testing set with the highest AUC of 0.975. Deep learning classifiers can be used to identify EHR progress notes pertaining to diabetes. In particular, the CNN-based classifier can achieve a higher AUC than an SVM-based classifier.