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KEGNI: knowledge graph enhanced framework for gene regulatory network inference.

Pengxiao Li1, Lin Li1, Jingminjie Nan2

  • 1Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.

Genome Biology
|September 22, 2025
PubMed
Summary
This summary is machine-generated.

We developed KEGNI, a novel framework for inferring gene regulatory networks (GRNs) from single-cell RNA sequencing data. KEGNI leverages knowledge graphs to enhance accuracy in identifying gene regulatory relationships and driver genes.

Keywords:
Gene regulatory networksKnowledge graphMulti-task learningScRNA-seqSelf-supervised learning

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Area of Science:

  • Computational Biology
  • Genomics
  • Bioinformatics

Background:

  • Gene regulatory networks (GRNs) are crucial for understanding cellular mechanisms.
  • Inferring cell type-specific GRNs is essential but challenging with complex biological data.
  • Existing methods often lack the ability to integrate prior biological knowledge effectively.

Purpose of the Study:

  • To present KEGNI (Knowledge graph-Enhanced Gene regulatory Network Inference), a novel framework for GRN inference.
  • To improve the accuracy and interpretability of GRN inference using single-cell RNA sequencing (scRNA-seq) data.
  • To demonstrate KEGNI's capability in identifying driver genes and elucidating regulatory mechanisms.

Main Methods:

  • KEGNI employs a knowledge-guided approach using a graph autoencoder.
  • It integrates a knowledge graph to capture and infer gene regulatory relationships.
  • The framework is designed to process scRNA-seq data, with potential for paired scRNA-seq and scATAC-seq data.

Main Results:

  • KEGNI demonstrated superior performance over existing methods in GRN inference.
  • The framework successfully identified driver genes across different cellular contexts.
  • KEGNI effectively elucidated complex regulatory mechanisms using integrated knowledge.

Conclusions:

  • KEGNI provides a powerful and accurate method for inferring cell type-specific GRNs.
  • The knowledge-guided approach enhances the understanding of gene regulation from scRNA-seq data.
  • KEGNI's modular design allows for flexible integration of diverse knowledge sources for various applications.