Can Large Language Models Enhance Predictions of Disease Progression? Investigating Through Disease Network Link Prediction

Large Language Models (LLMs) have made significant strides in various tasks, yet their effectiveness in predicting disease progression remains relatively unexplored. To fill this gap, we use LLMs and employ advanced graph prompting and Retrieval-Augmented Generation (RAG) to predict disease comorbidity within disease networks. Specifically, we introduce a disease Comorbidity prediction model using LLM, named ComLLM, which leverages domain knowledge to enhance the prediction performance. Based on the comprehensive experimental results, ComLLM consistently outperforms conventional models, such as Graph Neural Networks, achieving average area under the curve (AUC) improvements of 10.70% and 6.07% over the best baseline models in two distinct disease networks. ComLLM is evaluated across multiple settings for disease progression prediction, employing various prompting strategies, including zero-shot, few-shot, Chain-of-Thought, graph prompting and RAG. Our results show that graph prompting and RAG enhance LLM performance in disease progression prediction tasks. ComLLM exhibits superior predictive capabilities and serves as a proofof-concept for LLM-based systems in disease progression prediction, highlighting its potential for broad applications in healthcare 1 .