A Hierarchical Multimodal Knowledge Graph for Neural Cell-Type-Specific Regulation Integrating Single-Cell Transcriptomics and Literature Evidence
The nervous system comprises highly diverse cell types governed by cell-type-specific molecular regulatory programs. However, regulatory evidence is scattered across unstructured literature and described using inconsistent cell-type nomenclature and granularity, hindering systematic integration and cross-study comparison. Here, we construct a neural-cell-centric multimodal knowledge graph that transforms fragmented regulatory evidence into a standardized, computable substrate. We establish a three-level hierarchical cell-type taxonomy anchored to the Cell Ontology (79 nodes), integrate two large-scale human brain single-cell transcriptomic datasets (over 4 million cells) to derive molecular fingerprints, and use a large language model to retain 25,812 curated regulatory evidence records from PubMed abstracts. The resulting Neo4j graph contains 41,532 directed relationships. For knowledge graph embedding, we export a deduplicated non-paper training subgraph containing 19,819 triples over 10,660 entities, supporting cell-type-specific link prediction that prioritizes candidate regulators and markers, illustrated here for microglia. This framework provides a structured basis for cross-study comparison, hypothesis generation and knowledge-guided reasoning in neural cell-type-specific regulation.
Authors
- Chuangyu Chen
- Hao Yu (ORCID: https://orcid.org/0000-0003-2793-7912)
- Xiaomin Ni (ORCID: https://orcid.org/0000-0003-4043-3292)
- Yang Zhang
- Yang Min
- Zhilan Xu
- Zhen Wang
Institutions
- Chinese Academy of Sciences (CN)
- Shenzhen Bay Laboratory (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2026-07-30
- DOI
- https://doi.org/10.3390/ijms27156842
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00