GraPPI: A Retrieve-Divide-Solve GraphRAG Framework for Large-scale Protein-protein Interaction Exploration

Fuente: arXiv
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Main Authors: Li, Ziwen, Chen, Xiang 'Anthony', Jeon, Youngseung
Format: Preprint
Published: 2025
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author Li, Ziwen
Chen, Xiang 'Anthony'
Jeon, Youngseung
author_facet Li, Ziwen
Chen, Xiang 'Anthony'
Jeon, Youngseung
contents Drug discovery (DD) has tremendously contributed to maintaining and improving public health. Hypothesizing that inhibiting protein misfolding can slow disease progression, researchers focus on target identification (Target ID) to find protein structures for drug binding. While Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have accelerated drug discovery, integrating models into cohesive workflows remains challenging. We conducted a user study with drug discovery researchers to identify the applicability of LLMs and RAGs in Target ID. We identified two main findings: 1) an LLM should provide multiple Protein-Protein Interactions (PPIs) based on an initial protein and protein candidates that have a therapeutic impact; 2) the model must provide the PPI and relevant explanations for better understanding. Based on these observations, we identified three limitations in previous approaches for Target ID: 1) semantic ambiguity, 2) lack of explainability, and 3) short retrieval units. To address these issues, we propose GraPPI, a large-scale knowledge graph (KG)-based retrieve-divide-solve agent pipeline RAG framework to support large-scale PPI signaling pathway exploration in understanding therapeutic impacts by decomposing the analysis of entire PPI pathways into sub-tasks focused on the analysis of PPI edges.
format Preprint
id arxiv_https___arxiv_org_abs_2501_16382
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle GraPPI: A Retrieve-Divide-Solve GraphRAG Framework for Large-scale Protein-protein Interaction Exploration
Li, Ziwen
Chen, Xiang 'Anthony'
Jeon, Youngseung
Quantitative Methods
Artificial Intelligence
Machine Learning
Drug discovery (DD) has tremendously contributed to maintaining and improving public health. Hypothesizing that inhibiting protein misfolding can slow disease progression, researchers focus on target identification (Target ID) to find protein structures for drug binding. While Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have accelerated drug discovery, integrating models into cohesive workflows remains challenging. We conducted a user study with drug discovery researchers to identify the applicability of LLMs and RAGs in Target ID. We identified two main findings: 1) an LLM should provide multiple Protein-Protein Interactions (PPIs) based on an initial protein and protein candidates that have a therapeutic impact; 2) the model must provide the PPI and relevant explanations for better understanding. Based on these observations, we identified three limitations in previous approaches for Target ID: 1) semantic ambiguity, 2) lack of explainability, and 3) short retrieval units. To address these issues, we propose GraPPI, a large-scale knowledge graph (KG)-based retrieve-divide-solve agent pipeline RAG framework to support large-scale PPI signaling pathway exploration in understanding therapeutic impacts by decomposing the analysis of entire PPI pathways into sub-tasks focused on the analysis of PPI edges.
title GraPPI: A Retrieve-Divide-Solve GraphRAG Framework for Large-scale Protein-protein Interaction Exploration
topic Quantitative Methods
Artificial Intelligence
Machine Learning
url https://arxiv.org/abs/2501.16382