# UniD3: A Knowledge Graph-Enhanced RAG Framework for Drug-Disease Discovery and Reasoning

arXiv: https://arxiv.org/abs/2606.01394 · HTML: https://mlsanity.com/paper/2606.01394/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and biomedical RAG, one of 15 directions in Retrieval-augmented generation.
- Builds on 21 of its 39 references that are in the map.
- First posted on arXiv 31 May 2026.

## Placed in

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

## Builds on (most cited first, 21 of 21)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [LLaMA: Open and Efficient Foundation Language Models](https://mlsanity.com/paper/2302.13971/) (2023)
- [BERTScore: Evaluating Text Generation with BERT](https://mlsanity.com/paper/1904.09675/) (2019)
- [From Local to Global: A Graph RAG Approach to Query-Focused Summarization](https://mlsanity.com/paper/2404.16130/) (2024)
- [A Prompt Pattern Catalog to Enhance Prompt Engineering with ChatGPT](https://mlsanity.com/paper/2302.11382/) (2023)
- [BioGPT: Generative Pre-trained Transformer for Biomedical Text Generation and Mining](https://mlsanity.com/paper/2210.10341/) (2022)
- [Datasets: A Community Library for Natural Language Processing](https://mlsanity.com/paper/2109.02846/) (2021)
- [LightRAG: Simple and Fast Retrieval-Augmented Generation](https://mlsanity.com/paper/2410.05779/) (2024)
- [HuatuoGPT-o1, Towards Medical Complex Reasoning with LLMs](https://mlsanity.com/paper/2412.18925/) (2024)
- [Retrieval-Augmented Generation with Graphs (GraphRAG)](https://mlsanity.com/paper/2501.00309/) (2024)
- [Medical Graph RAG: Towards Safe Medical Large Language Model via Graph Retrieval-Augmented Generation](https://mlsanity.com/paper/2408.04187/) (2024)
- [Curated LLM: Synergy of LLMs and Data Curation for tabular augmentation in low-data regimes](https://mlsanity.com/paper/2312.12112/) (2023)
- [DALK: Dynamic Co-Augmentation of LLMs and KG to answer Alzheimer's Disease Questions with Scientific Literature](https://mlsanity.com/paper/2405.04819/) (2024)
- [Synthetic Dialogue Dataset Generation using LLM Agents](https://mlsanity.com/paper/2401.17461/) (2024)
- [BiomedRAG: A Retrieval Augmented Large Language Model for Biomedicine](https://mlsanity.com/paper/2405.00465/) (2024)
- [MiniRAG: Towards Extremely Simple Retrieval-Augmented Generation](https://mlsanity.com/paper/2501.06713/) (2025)
- [ArchRAG: Attributed Community-based Hierarchical Retrieval-Augmented Generation](https://mlsanity.com/paper/2502.09891/) (2025)
- [BioREx: Improving Biomedical Relation Extraction by Leveraging Heterogeneous Datasets](https://mlsanity.com/paper/2306.11189/) (2023)
- [Adaptive Context Length Optimization with Low-Frequency Truncation for Multi-Agent Reinforcement Learning](https://mlsanity.com/paper/2510.26389/) (2025)
- [scDrugMap: Benchmarking Large Foundation Models for Drug Response Prediction](https://mlsanity.com/paper/2505.05612/) (2025)

## Abstract (arXiv)

Systematic characterization of drug-disease relationships is essential for drug discovery and repurposing, yet is hindered by the heterogeneity and rapid growth of biomedical literature. Existing datasets rely on labor-intensive curation and are often incomplete, while LLM-only approaches suffer from hallucination and weak evidence grounding. We introduce UniD3, a unified framework that integrates Large Language Models with Knowledge Graph-enhanced Retrieval-Augmented Generation (KG-RAG) to extract, organize, and validate drug-disease knowledge across Drug-Disease Matching (DDM), Drug Effectiveness Assessment (DEA), and Drug-Target Analysis (DTA). UniD3 processes 157,849 PubMed articles with Llama 3.3-70B and constructs knowledge graphs via a dual-stage strategy combining paper-level extraction with KG-level consolidation centered on drug and disease entities. These graphs support KG-RAG-based generation of structured datasets, evaluated through external benchmarks, fuzzy matching with curated resources, and clinician review. UniD3 produces six knowledge graphs and large-scale datasets, including 28,915 DDM, 15,042 DEA, and over 4,000 DTA QA pairs. External validation shows strong performance (F1: 0.85-0.87 for DDM/DEA; 0.82 for DTA), with clinician review confirming high reliability (AUROC = 0.90). KG-RAG-augmented models outperform standalone LLMs, and the UniD3 chatbot enables interpretable, citation-supported exploration of drug-disease relationships. UniD3 provides a scalable, extensible framework for transforming unstructured biomedical literature into high-quality, structured drug-disease knowledge, supporting AI-driven discovery, repurposing, and precision medicine.