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.

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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
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article

A Hierarchical Multimodal Knowledge Graph for Neural Cell-Type-Specific Regulation Integrating Single-Cell Transcriptomics and Literature Evidence

Chuangyu Chen, Hao Yu, Xiaomin Ni, Yang Zhang et al.
International Journal of Molecular Sciences
Single-cell and spatial transcriptomics
article

A Hierarchical Multimodal Knowledge Graph for Neural Cell-Type-Specific Regulation Integrating Single-Cell Transcriptomics and Literature Evidence

Chuangyu Chen, Hao Yu, Xiaomin Ni, Yang Zhang, Yang Min, Zhilan Xu, Zhen Wang
article en

Abstract

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.

International Journal of Molecular SciencesVol. 27(15)
Chinese Academy of Sciences (CN), Shenzhen Bay Laboratory (CN), Shenzhen Institutes of Advanced Technology (CN), University of Chinese Academy of Sciences (CN)
Openalex Percentile: Top 15%
Single-cell and spatial transcriptomics
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