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

arXiv: https://arxiv.org/abs/2501.16382 · HTML: https://mlsanity.com/paper/2501.16382/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Placed in Medical and biomedical RAG, one of 15 directions in Retrieval-augmented generation.
- Builds on 25 of its 47 references that are in the map.
- First posted on arXiv 24 Jan 2025.

## Placed in

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

## Builds on (most cited first, 25 of 25)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [BERTScore: Evaluating Text Generation with BERT](https://mlsanity.com/paper/1904.09675/) (2019)
- [Billion-scale similarity search with GPUs](https://mlsanity.com/paper/1702.08734/) (2017)
- [Generalization through Memorization: Nearest Neighbor Language Models](https://mlsanity.com/paper/1911.00172/) (2019)
- [Harnessing the Power of LLMs in Practice: A Survey on ChatGPT and Beyond](https://mlsanity.com/paper/2304.13712/) (2023)
- [Does the Whole Exceed its Parts? The Effect of AI Explanations on Complementary Team Performance](https://mlsanity.com/paper/2006.14779/) (2020)
- [Reasoning on Graphs: Faithful and Interpretable Large Language Model Reasoning](https://mlsanity.com/paper/2310.01061/) (2023)
- [Large Language Models are Zero-Shot Rankers for Recommender Systems](https://mlsanity.com/paper/2305.08845/) (2023)
- [Effect of Confidence and Explanation on Accuracy and Trust Calibration in AI-Assisted Decision Making](https://mlsanity.com/paper/2001.02114/) (2020)
- [Teach Me to Explain: A Review of Datasets for Explainable Natural Language Processing](https://mlsanity.com/paper/2102.12060/) (2021)
- [Do LLMs Understand User Preferences? Evaluating LLMs On User Rating Prediction](https://mlsanity.com/paper/2305.06474/) (2023)
- [LongRAG: Enhancing Retrieval-Augmented Generation with Long-context LLMs](https://mlsanity.com/paper/2406.15319/) (2024)
- [GPT4Rec: A Generative Framework for Personalized Recommendation and User Interests Interpretation](https://mlsanity.com/paper/2304.03879/) (2023)
- [Boosting Language Models Reasoning with Chain-of-Knowledge Prompting](https://mlsanity.com/paper/2306.06427/) (2023)
- [QED: A Framework and Dataset for Explanations in Question Answering](https://mlsanity.com/paper/2009.06354/) (2020)
- [Large Language Models Help Humans Verify Truthfulness -- Except When They Are Convincingly Wrong](https://mlsanity.com/paper/2310.12558/) (2023)
- [In Search of Verifiability: Explanations Rarely Enable Complementary Performance in AI-Advised Decision Making](https://mlsanity.com/paper/2305.07722/) (2023)
- [BioRAG: A RAG-LLM Framework for Biological Question Reasoning](https://mlsanity.com/paper/2408.01107/) (2024)
- [BiomedRAG: A Retrieval Augmented Large Language Model for Biomedicine](https://mlsanity.com/paper/2405.00465/) (2024)
- [Human Interpretation of Saliency-based Explanation Over Text](https://mlsanity.com/paper/2201.11569/) (2022)
- [ProtoTEx: Explaining Model Decisions with Prototype Tensors](https://mlsanity.com/paper/2204.05426/) (2022)
- [Understand the Dynamic World: An End-to-End Knowledge Informed Framework for Open Domain Entity State Tracking](https://mlsanity.com/paper/2304.13854/) (2023)

## Built on by (most cited first, 3 of 3)

- [SARA: Selective and Adaptive Retrieval-augmented Generation with Context Compression](https://mlsanity.com/paper/2507.05633/) (2025)
- [Taxonomic Reasoning for Rare Arthropods: Combining Dense Image Captioning and RAG for Interpretable Classification](https://mlsanity.com/paper/2503.10886/) (2025)
- [RAGPPI: RAG Benchmark for Protein-Protein Interactions in Drug Discovery](https://mlsanity.com/paper/2505.23823/) (2025)

## Abstract (arXiv)

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.