# Towards Interpretable Drug-Drug Interaction Prediction: A Graph-Based Approach with Molecular and Network-Level Explanations

arXiv: https://arxiv.org/abs/2507.09173 · HTML: https://mlsanity.com/paper/2507.09173/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 11 of its 65 references that are in the map.
- First posted on arXiv 12 Jul 2025.

## Builds on (most cited first, 11 of 11)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [Link Prediction Based on Graph Neural Networks](https://mlsanity.com/paper/1802.09691/) (2018)
- [Graph-based Molecular Representation Learning](https://mlsanity.com/paper/2207.04869/) (2022)
- [RGB-D Saliency Detection via Cascaded Mutual Information Minimization](https://mlsanity.com/paper/2109.07246/) (2021)
- [SumGNN: Multi-typed Drug Interaction Prediction via Efficient Knowledge Graph Summarization](https://mlsanity.com/paper/2010.01450/) (2020)
- [Drug-Drug Interaction Prediction Based on Knowledge Graph Embeddings and Convolutional-LSTM Network](https://mlsanity.com/paper/1908.01288/) (2019)
- [MR-GNN: Multi-Resolution and Dual Graph Neural Network for Predicting Structured Entity Interactions](https://mlsanity.com/paper/1905.09558/) (2019)
- [CASTER: Predicting Drug Interactions with Chemical Substructure Representation](https://mlsanity.com/paper/1911.06446/) (2019)
- [Emerging Drug Interaction Prediction Enabled by Flow-based Graph Neural Network with Biomedical Network](https://mlsanity.com/paper/2311.09261/) (2023)
- [Accurate and interpretable drug-drug interaction prediction enabled by knowledge subgraph learning](https://mlsanity.com/paper/2311.15056/) (2023)

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

- [Bridging Distance and Spectral Positional Encodings via Anchor-Based Diffusion Geometry Approximation](https://mlsanity.com/paper/2601.04517/) (2026)
- [CoFEND: A Cross-Modal Fusion End-to-End Network for Cold-Start Drug-Drug Interaction Prediction](https://mlsanity.com/paper/2607.02928/) (2026)
- [Towards AI-Driven Nanomedicine Discovery: A Benchmark and Multimodal Learning Framework for Nano Self-Assembly Prediction](https://mlsanity.com/paper/2609.04278/) (2026)

## Abstract (arXiv)

Drug-drug interactions (DDIs) represent a critical challenge in pharmacology, often leading to adverse drug reactions with significant implications for patient safety and healthcare outcomes. While graph-based methods have achieved strong predictive performance, most approaches treat drug pairs independently, overlooking the complex, context-dependent interactions unique to drug pairs. Additionally, these models struggle to integrate biological interaction networks and molecular-level structures to provide meaningful mechanistic insights. In this study, we propose MolecBioNet, a novel graph-based framework that integrates molecular and biomedical knowledge for robust and interpretable DDI prediction. By modeling drug pairs as unified entities, MolecBioNet captures both macro-level biological interactions and micro-level molecular influences, offering a comprehensive perspective on DDIs. The framework extracts local subgraphs from biomedical knowledge graphs and constructs hierarchical interaction graphs from molecular representations, leveraging classical graph neural network methods to learn multi-scale representations of drug pairs. To enhance accuracy and interpretability, MolecBioNet introduces two domain-specific pooling strategies: context-aware subgraph pooling (CASPool), which emphasizes biologically relevant entities, and attention-guided influence pooling (AGIPool), which prioritizes influential molecular substructures. The framework further employs mutual information minimization regularization to enhance information diversity during embedding fusion. Experimental results demonstrate that MolecBioNet outperforms state-of-the-art methods in DDI prediction, while ablation studies and embedding visualizations further validate the advantages of unified drug pair modeling and multi-scale knowledge integration.