GCLink: a graph contrastive link prediction framework for gene regulatory network inference.

Weiming Yu, Zerun Lin, Miaofang Lan, Le Ou-Yang
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Abstract

Motivation: Gene regulatory networks (GRNs) unveil the intricate interactions among genes, pivotal in elucidating the complex biological processes within cells. The advent of single-cell RNA-sequencing (scRNA-seq) enables the inference of GRNs at single-cell resolution. However, the majority of current supervised network inference methods typically concentrate on predicting pairwise gene regulatory interaction, thus failing to fully exploit correlations among all genes and exhibiting limited generalization performance.

Results: To address these issues, we propose a graph contrastive link prediction (GCLink) model to infer potential gene regulatory interactions from scRNA-seq data. Based on known gene regulatory interactions and scRNA-seq data, GCLink introduces a graph contrastive learning strategy to aggregate the feature and neighborhood information of genes to learn their representations. This approach reduces the dependence of our model on sample size and enhance its ability in predicting potential gene regulatory interactions. Extensive experiments on real scRNA-seq datasets demonstrate that GCLink outperforms other state-of-the-art methods in most cases. Furthermore, by pretraining GCLink on a source cell line with abundant known regulatory interactions and fine-tuning it on a target cell line with limited amount of known interactions, our GCLink model exhibits good performance in GRN inference, demonstrating its effectiveness in inferring GRNs from datasets with limited known interactions.

Availability and implementation: The source code and data are available at https://github.com/Yoyiming/GCLink.

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GCLink:一个用于基因调控网络推断的图对比链接预测框架。
动机:基因调控网络(grn)揭示了基因之间复杂的相互作用,在阐明细胞内复杂的生物过程中起着关键作用。单细胞rna测序(scRNA-seq)的出现使得在单细胞分辨率上推断grn成为可能。然而,目前大多数有监督的网络推理方法通常集中在预测两两基因调控相互作用上,因此不能充分利用所有基因之间的相关性,并且泛化性能有限。结果:为了解决这些问题,我们提出了一个图对比链接预测(GCLink)模型,从scRNA-seq数据推断潜在的基因调控相互作用。GCLink基于已知的基因调控相互作用和scRNA-seq数据,引入了一种图对比学习策略,通过聚合基因的特征和邻域信息来学习它们的表示。这种方法减少了我们的模型对样本量的依赖,增强了其预测潜在基因调控相互作用的能力。在真实的scRNA-seq数据集上进行的大量实验表明,GCLink在大多数情况下优于其他最先进的方法。此外,通过在具有丰富已知调控相互作用的源细胞系上预训练GCLink,并在具有有限已知相互作用的目标细胞系上对其进行微调,我们的GCLink模型在GRN推断中表现出良好的性能,证明了其在从具有有限已知相互作用的数据集推断GRN方面的有效性。可用性:源代码和数据可在https://github.com/Yoyiming/GCLink.Supplementary上获得:补充数据可在Bioinformatics在线上获得。
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