# Explainable Biomedical Hypothesis Generation via Retrieval Augmented Generation enabled Large Language Models

arXiv: https://arxiv.org/abs/2407.12888 · HTML: https://mlsanity.com/paper/2407.12888/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Placed in Medical and biomedical RAG, one of 15 directions in Retrieval-augmented generation.
- First posted on arXiv 17 Jul 2024.

## Placed in

- Retrieval-augmented generation / [Medical and biomedical RAG](https://mlsanity.com/rag/medical-and-biomedical-rag/)

## Built on by (most cited first, 4 of 4)

- [Retrieval-Augmented Generation with Graphs (GraphRAG)](https://mlsanity.com/paper/2501.00309/) (2024)
- [Position: Multimodal Large Language Models Can Significantly Advance Scientific Reasoning](https://mlsanity.com/paper/2502.02871/) (2025)
- [Biomedical Knowledge Graph: A Survey of Domains, Tasks, and Real-World Applications](https://mlsanity.com/paper/2501.11632/) (2025)
- [Biomedical Hypothesis Explainability with Graph-Based Context Retrieval](https://mlsanity.com/paper/2511.05498/) (2025)

## Abstract (arXiv)

The vast amount of biomedical information available today presents a significant challenge for investigators seeking to digest, process, and understand these findings effectively. Large Language Models (LLMs) have emerged as powerful tools to navigate this complex and challenging data landscape. However, LLMs may lead to hallucinatory responses, making Retrieval Augmented Generation (RAG) crucial for achieving accurate information. In this protocol, we present RUGGED (Retrieval Under Graph-Guided Explainable disease Distinction), a comprehensive workflow designed to support investigators with knowledge integration and hypothesis generation, identifying validated paths forward. Relevant biomedical information from publications and knowledge bases are reviewed, integrated, and extracted via text-mining association analysis and explainable graph prediction models on disease nodes, forecasting potential links among drugs and diseases. These analyses, along with biomedical texts, are integrated into a framework that facilitates user-directed mechanism elucidation as well as hypothesis exploration through RAG-enabled LLMs. A clinical use-case demonstrates RUGGED's ability to evaluate and recommend therapeutics for Arrhythmogenic Cardiomyopathy (ACM) and Dilated Cardiomyopathy (DCM), analyzing prescribed drugs for molecular interactions and unexplored uses. The platform minimizes LLM hallucinations, offers actionable insights, and improves the investigation of novel therapeutics.