arXiv:2505.03853q-bio.QMcs.AI2025-05IJCAI被引 4

用基因描述和序列构建图模型,预测基因扰动效果

GRAPE: Heterogeneous Graph Representation Learning for Genetic Perturbation with Coding and Non-Coding Biotype

  • 结合基因描述与序列特征初始化表示,引入基因生物型差异
  • 在多个公开数据集上表现优于现有方法,提升预测精度
  • 适合基因功能研究、药物靶点发现等生物信息学应用

预测基因扰动可提前识别关键基因,显著提高实验效率。基因是细胞生命的基础,构建基因调控网络(GRN)对理解与预测基因扰动效应至关重要。然而,现有方法未能充分利用基因相关信息,仅依赖简单指标构建粗粒度GRN,且忽略不同生物型的功能差异,限制了潜在基因互作的捕捉能力。本文利用预训练大语言模型和DNA序列模型,分别提取基因描述与序列特征作为基因表示初始化;首次在基因扰动任务中引入基因生物型信息,模拟不同生物型基因在调控过程中的差异作用,并通过图结构学习(GSL)捕获隐含基因关系。提出GRAPE模型,一种异构图神经网络(HGNN),结合描述与序列特征初始化,建模不同生物型基因的差异化角色,并通过动态优化GRN实现精准预测。在公开数据集上的实验表明,该方法达到当前最优性能。

原文摘要 · Abstract (English)

Predicting genetic perturbations enables the identification of potentially crucial genes prior to wet-lab experiments, significantly improving overall experimental efficiency. Since genes are the foundation of cellular life, building gene regulatory networks (GRN) is essential to understand and predict the effects of genetic perturbations. However, current methods fail to fully leverage gene-related information, and solely rely on simple evaluation metrics to construct coarse-grained GRN. More importantly, they ignore functional differences between biotypes, limiting the ability to capture potential gene interactions. In this work, we leverage pre-trained large language model and DNA sequence model to extract features from gene descriptions and DNA sequence data, respectively, which serve as the initialization for gene representations. Additionally, we introduce gene biotype information for the first time in genetic perturbation, simulating the distinct roles of genes with different biotypes in regulating cellular processes, while capturing implicit gene relationships through graph structure learning (GSL). We propose GRAPE, a heterogeneous graph neural network (HGNN) that leverages gene representations initialized with features from descriptions and sequences, models the distinct roles of genes with different biotypes, and dynamically refines the GRN through GSL. The results on publicly available datasets show that our method achieves state-of-the-art performance.

基因调控图神经网络生物信息学

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