药理学知识图谱:药物再利用是否需要化学结构? / Pharmacology Knowledge Graphs: Do We Need Chemical Structure for Drug Repurposing?
1️⃣ 一句话总结
这项研究发现,在基于知识图谱预测药物新用途时,使用药物的网络拓扑关系和蛋白质信息比直接使用其详细的化学结构效果更好、更高效,表明复杂的化学结构模型并非必要。
The contributions of model complexity, data volume, and feature modalities to knowledge graph-based drug repurposing remain poorly quantified under rigorous temporal validation. We constructed a pharmacology knowledge graph from ChEMBL 36 comprising 5,348 entities including 3,127 drugs, 1,156 proteins, and 1,065 indications. A strict temporal split was enforced with training data up to 2022 and testing data from 2023 to 2025, together with biologically verified hard negatives mined from failed assays and clinical trials. We benchmarked five knowledge graph embedding models and a standard graph neural network with 3.44 million parameters that incorporates drug chemical structure using a graph attention encoder and ESM-2 protein embeddings. Scaling experiments ranging from 0.78 to 9.75 million parameters and from 25 to 100 percent of the data, together with feature ablation studies, were used to isolate the contributions of model capacity, graph density, and node feature modalities. Removing the graph attention based drug structure encoder and retaining only topological embeddings combined with ESM-2 protein features improved drug protein PR-AUC from 0.5631 to 0.5785 while reducing VRAM usage from 5.30 GB to 353 MB. Replacing the drug encoder with Morgan fingerprints further degraded performance, indicating that explicit chemical structure representations can be detrimental for predicting pharmacological network interactions. Increasing model size beyond 2.44 million parameters yielded diminishing returns, whereas increasing training data consistently improved performance. External validation confirmed 6 of the top 14 novel predictions as established therapeutic indications. These results show that drug pharmacological behavior can be accurately predicted using target-centric information and drug network topology alone, without requiring explicit chemical structure representations.
药理学知识图谱:药物再利用是否需要化学结构? / Pharmacology Knowledge Graphs: Do We Need Chemical Structure for Drug Repurposing?
这项研究发现,在基于知识图谱预测药物新用途时,使用药物的网络拓扑关系和蛋白质信息比直接使用其详细的化学结构效果更好、更高效,表明复杂的化学结构模型并非必要。
源自 arXiv: 2603.01537