AutoRD: An Automatic and End-to-End System for Rare Disease Knowledge Graph Construction Based on Ontologies-enhanced Large Language Models

Objectives: Our objective is to create an end-to-end system called AutoRD, which automates extracting information from clinical text about rare diseases. We have conducted various tests to evaluate the performance of AutoRD and highlighted its strengths and limitations in this paper. Materials and Methods: Our system, AutoRD, is a software pipeline involving data preprocessing, entity extraction, relation extraction, entity calibration, and knowledge graph construction. We implement this using large language models and medical knowledge graphs developed from open-source medical ontologies. We quantitatively evaluate our system on entity extraction, relation extraction, and the performance of knowledge graph construction. Results: AutoRD achieves an overall F1 score of 47.3%, a 14.4% improvement compared to the base LLM. In detail, AutoRD achieves an overall entity extraction F1 score of 56.1% (rare_disease: 83.5%, disease: 35.8%, symptom_and_sign: 46.1%, anaphor: 67.5%) and an overall relation extraction F1 score of 38.6% (produces: 34.7%, increases_risk_of: 12.4%, is_a: 37.4%, is_acronym: 44.1%, is_synonym: 16.3%, anaphora: 57.5%). Our qualitative experiment also demonstrates that the performance in constructing the knowledge graph is commendable. Discussion: AutoRD demonstrates the potential of LLM applications in rare disease detection. This improvement is attributed to several design, including the integration of ontologies-enhanced LLMs. Conclusion: AutoRD is an automated end-to-end system for extracting rare disease information from text to build knowledge graphs. It uses ontologies-enhanced LLMs for a robust medical knowledge base. The superior performance of AutoRD is validated by experimental evaluations, demonstrating the potential of LLMs in healthcare.

GraphCare: Enhancing Healthcare Predictions with Open-World Personalized Knowledge Graphs

Clinical predictive models often rely on patients electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose GraphCare, an open-world framework that leverages external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to generate patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed BAT graph neural network GNN for healthcare predictions. We evaluate GraphCare on two public datasets: MIMIC-III and MIMIC-IV. Our method outperforms baseline models in four vital healthcare prediction tasks: mortality, readmission, length-of-stay, and drug recommendation, improving AUROC on MIMIC-III by average margins of 10.4%, 3.8%, 2.0%, and 1.5%, respectively. Notably, GraphCare demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of GraphCare in generating personalized KGs for promoting personalized medicine.

MedML: Fusing Medical Knowledge and Machine Learning Models for Early Pediatric COVID-19 Hospitalization and Severity Prediction

The COVID-19 pandemic has caused devastating economic and social disruption, straining the resources of healthcare institutions worldwide. This has led to a nationwide call for models to predict hospitalization and severe illness in patients with COVID-19 to inform distribution of limited healthcare resources. We respond to one of these calls specific to the pediatric population. To address this challenge, we study two prediction tasks for the pediatric population using electronic health records: 1) predicting which children are more likely to be hospitalized, and 2) among hospitalized children, which individuals are more likely to develop severe symptoms. We respond to the national Pediatric COVID-19 data challenge with a novel machine learning model, MedML. MedML extracts the most predictive features based on medical knowledge and propensity scores from over 6 million medical concepts and incorporates the inter-feature relationships between heterogeneous medical features via graph neural networks (GNN). We evaluate MedML across 143,605 patients for the hospitalization prediction task and 11,465 patients for the severity prediction task using data from the National Cohort Collaborative (N3C) dataset. We also report detailed group-level and individual-level feature importance analyses to evaluate the model interpretability. MedML achieves up to a 7% higher AUROC score and up to a 14% higher AUPRC score compared to the best baseline machine learning models and performs well across all nine national geographic regions and over all three-month spans since the start of the pandemic. Our cross-disciplinary research team has developed a method of incorporating clinical domain knowledge as the framework for a new type of machine learning model that is more predictive and explainable than current state-of-the-art data-driven feature selection methods.