MolBioKG: Grounding Out-of-Graph Molecules in Biomedical Knowledge Graphs via Multi-Resolution Structural Anchoring

Computer Science > Artificial Intelligence [Submitted on 7 Aug 2026] MolBioKG: Grounding Out-of-Graph Molecules in Biomedical Knowledge Graphs via Multi-Resolution Structural Anchoring Yiming Zhang, Hikaru Shindo, Shuan Chen, Kaushalya Madhawa, Jun Jin Choong, Yuna Oikawa, Takashi Fujiwara, Keisuke Ozawa Biomedical knowledge graphs (KGs) accelerate drug discovery, but standard pipelines assume query molecules already exist as graph entities, leaving unregistered molecules disconnected. We address this cold-start challenge, termed the out-of-graph molecule problem, by introducing MolBioKG. This two-layer system grounds unseen molecules in biomedical evidence via multi-resolution structural anchoring. It connects an index of 2.74 million molecules (represented by scaffolds, fragments, functional groups, and fingerprints) to a 9.6-million-edge KG. Given only a SMILES string, MolBioKG retrieves structurally related graph entities and traverses their biomedical neighborhoods without task-specific training. It features two inference mechanisms: static multi-anchor retrieval using Reciprocal Rank Fusion, and Adapt-KG, a tool-using LLM policy for adaptive traversal. Evaluated across in-graph link recovery, complex multi-hop reasoning, and out-of-graph generalization, MolBioKG outperforms strong baselines. Notably, it raises Hits@10 from 0.585 to 0.876 in multi-hop reasoning and out-of-graph target recall from 0.145 to 0.269, all while ensuring predictions retain traceable structural anchors and source-attributed KG evidence. Comments: Preprint Subjects: Artificial Intelligence (cs.AI); Machine Learning (cs.LG) Cite as: arXiv:2608.06713 [cs.AI]   (or arXiv:2608.06713v1 [cs.AI] for this version)   https://doi.org/10.48550/arXiv.2608.06713 Focus to learn more Submission history From: Hikaru Shindo [view email] [v1] Fri, 7 Aug 2026 02:12:52 UTC (1,136 KB) Access Paper: HTML (experimental) view license Current browse context: cs.AI < prev   |   next > new | recent | 2026-08 Change to browse by: cs cs.LG References & Citations NASA ADS Google Scholar Semantic Scholar Export BibTeX Citation Bookmark Bibliographic Tools Bibliographic and Citation Tools Bibliographic Explorer Toggle Bibliographic Explorer (What is the Explorer?) Connected Papers Toggle Connected Papers (What is Connected Papers?) Litmaps Toggle Litmaps (What is Litmaps?) scite.ai Toggle scite Smart Citations (What are Smart Citations?) Code, Data, Media Demos Related Papers About arXivLabs Which authors of this paper are endorsers? | Disable MathJax (What is MathJax?)