Evidence mapPaperPMID 40993718Full record

ArticleGenome biology2025

scKAN: interpretable single-cell analysis for cell-type-specific gene discovery and drug repurposing via Kolmogorov-Arnold networks.

Haohuai He, Zhenchao Tang, Guanxing Chen, Fan Xu, Yao Hu, Yinglan Feng, Jibin Wu, Yu-An Huang, Zhi-An Huang, Kay Chen Tan

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Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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2 citing papers in PubMed.

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5 · Who and what money

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10 authors.

Haohuai HeDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Zhenchao TangArtificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, China.
Guanxing ChenDepartment of Computer Science, City University of Hong Kong (Dongguan), Dongguan, 523000, China.
Fan XuDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Yao HuDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Yinglan FengDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Jibin WuDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Yu-An HuangSchool of Computer Science, Northwestern Polytechnical University, Xi'an, 710000, China. yuanhuang@nwpu.edu.cn.
Zhi-An HuangDepartment of Computer Science, City University of Hong Kong (Dongguan), Dongguan, 523000, China. huang.za@cityu-dg.edu.cn.
Kay Chen TanDepartment of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR, China.

Funding

City University of Hong Kong (Dongguan) New Faculty Start-up Fund B01040000138Fundamental Research Funds for the Central Universities G2023KY05102Guangdong Basic and Applied Basic Research Foundation 2025A1515012944 and 2024A1515011984National Natural Science Foundation of China 62572413, 62202399, U21A20512, and 62472353Research Grants Council of the Hong Kong SAR C5052-23G, PolyU15229824, PolyU15218622, and PolyU15215623The Hong Kong Polytechnic University P0053758, P0051130, and P0052694
6 · The paper itself

Abstract

backgroundAnalysis of single-cell RNA sequencing (scRNA-seq) data has revolutionized our understanding of cellular heterogeneity, yet current approaches face challenges in efficiency, interpretability, and connecting molecular insights to therapeutic applications. Despite advances in deep learning methods, identifying cell-type-specific functional gene sets remains difficult.

resultsIn this study, we present scKAN, an interpretable framework for scRNA-seq analysis with two primary goals: accurate cell-type annotation and the discovery of cell-type-specific marker genes and gene sets. The key innovation is using the learnable activation curves of the Kolmogorov-Arnold network to model gene-to-cell relationships. This approach provides a more direct way to visualize and interpret these specific interactions compared to the aggregated weighting schemes typical of attention mechanisms. This architecture achieves superior performance in cell-type annotation, with a 6.63% improvement in macro F1 score over state-of-the-art methods. Additionally, it enables the systematic identification of functionally coherent cell-type-specific gene sets. We demonstrate the framework's translational potential through a case study on pancreatic ductal adenocarcinoma, where gene signatures identified by scKAN led to a potential drug repurposing candidate, whose binding stability was supported by molecular dynamics simulations.

conclusionsOur work establishes scKAN as an efficient and interpretable framework that effectively bridges single-cell analysis with drug discovery. By combining lightweight architecture with the ability to uncover nuanced biological patterns, our approach offers an interpretable method for translating large-scale single-cell data into actionable therapeutic strategies. This approach provides a robust foundation for accelerating the identification of cell-type-specific targets in complex diseases.

Indexed as

Drug RepositioningSingle-Cell AnalysisGene Regulatory NetworksHumansSequence Analysis, RNADrug repurposingInterpretable AIKolmogorov-Arnold networksMarker gene discoverySingle-cell analysis

Identifiers

PMID40993718
PMCPMC12462335

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.