AnomalGRN: deciphering single-cell gene regulation network with graph anomaly detection.

IF 4.5 1区 生物学 Q1 BIOLOGY BMC Biology Pub Date : 2025-03-11 DOI:10.1186/s12915-025-02177-z
Zhecheng Zhou, Jinhang Wei, Mingzhe Liu, Linlin Zhuo, Xiangzheng Fu, Quan Zou
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Abstract

Background: Single-cell RNA sequencing (scRNA-seq) is now essential for cellular-level gene expression studies and deciphering complex gene regulatory mechanisms. Deep learning methods, when combined with scRNA-seq technology, transform gene regulation research into graph link prediction tasks. However, these methods struggle to mitigate the impact of noisy data in gene regulatory networks (GRNs) and address the significant imbalance between positive and negative links.

Results: Consequently, we introduce the AnomalGRN model, focusing on heterogeneity and sparsification to elucidate complex regulatory mechanisms within GRNs. Initially, we consider gene pairs as nodes to construct new networks, thereby converting gene regulation prediction into a node prediction task. Considering the imbalance between positive and negative links in GRNs, we further adapt this issue into a graph anomaly detection (GAD) task, marking the first application of anomaly detection to GRN analysis. Introducing the cosine metric rule enables the AnomalGRN model to differentiate between homogeneity and heterogeneity among nodes in the reconstructed GRNs. The adoption of graph structure sparsification technology reduces noisy data impact and optimizes node representation.

Conclusions:

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利用图异常检测技术破解单细胞基因调控网络。
背景:单细胞RNA测序(scRNA-seq)现在对于细胞水平的基因表达研究和破译复杂的基因调控机制是必不可少的。深度学习方法与scRNA-seq技术相结合,将基因调控研究转化为图链接预测任务。然而,这些方法难以减轻基因调控网络(grn)中噪声数据的影响,并解决积极和消极联系之间的显着不平衡。因此,我们引入了反常grn模型,重点关注grn的异质性和稀疏性,以阐明grn内部复杂的调控机制。首先,我们将基因对作为节点构建新的网络,从而将基因调控预测转化为节点预测任务。考虑到GRN中正链路和负链路之间的不平衡,我们进一步将这一问题引入到图异常检测(GAD)任务中,标志着异常检测首次应用于GRN分析。引入余弦度量规则使反常grn模型能够区分重构grn中节点的同质性和异质性。采用图结构稀疏化技术,减少了噪声数据的影响,优化了节点表示。结论:
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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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