融合多源网络与表达数据,用图变压器提升基因调控网络推断精度。
A Novel Graph Transformer Framework for Gene Regulatory Network Inference
- 用自编码器捕捉基因表达模式,结合随机游走生成文本化先验知识
- 通过BERT编码先验结构与位置信息,增强基因在图中的表征能力
- 基于图变压器模型,在多个数据集上显著超越现有方法
基因调控网络(GRN)推断是解析复杂生物系统机制的基础。将两基因间可能的调控关系建模为链接预测问题。仅依赖基因共表达数据进行推断易受噪声干扰,难以反映真实生物互作。现有方法在重构阶段面临诸多挑战。为此,本文提出一种融合多源推断网络的图变压器框架GT-GRN。首先,利用自编码器从原始数据中提取基因表达模式,保留复杂生物信号;其次,通过随机游走将已有GRN结构转换为类似文本的表示,并使用BERT模型生成跨网络的全局基因嵌入;同时引入输入网络节点的位置编码,以更好定位每个基因在图中的位置。上述嵌入被整合进图变压器模型中,用于更准确地推断GRN。实验表明,GT-GRN在多个数据集上显著优于现有方法,展现出更高的准确性和鲁棒性。
原文摘要 · Abstract (English)
The inference of gene regulatory networks (GRNs) is a foundational stride towards deciphering the fundamentals of complex biological systems. Inferring a possible regulatory link between two genes can be formulated as a link prediction problem. Inference of GRNs via gene coexpression profiling data may not always reflect true biological interactions, as its susceptibility to noise and misrepresenting true biological regulatory relationships. Most GRN inference methods face several challenges in the network reconstruction phase. Therefore, it is important to encode gene expression values, leverege the prior knowledge gained from the available inferred network structures and positional informations of the input network nodes towards inferring a better and more confident GRN network reconstruction. In this paper, we explore the integration of multiple inferred networks to enhance the inference of Gene Regulatory Networks (GRNs). Primarily, we employ autoencoder embeddings to capture gene expression patterns directly from raw data, preserving intricate biological signals. Then, we embed the prior knowledge from GRN structures transforming them into a text-like representation using random walks, which are then encoded with a masked language model, BERT, to generate global embeddings for each gene across all networks. Additionally, we embed the positional encodings of the input gene networks to better identify the position of each unique gene within the graph. These embeddings are integrated into graph transformer-based model, termed GT-GRN, for GRN inference. The GT-GRN model effectively utilizes the topological structure of the ground truth network while incorporating the enriched encoded information. Experimental results demonstrate that GT-GRN significantly outperforms existing GRN inference methods, achieving superior accuracy and highlighting the robustness of our approach.
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