用基因本体图增强BERT,实现通用基因功能预测
GoBERT: Gene Ontology Graph Informed BERT for Universal Gene Function Prediction
- 基于基因本体图构建双预训练任务,捕捉显性与隐性功能关系
- 在多个基因数据集上显著提升新功能预测准确率
- 适合生物信息学、基因功能研究者使用
解析基因及其产物的功能对医学研究、进化生物学和环境科学至关重要,但传统发现依赖昂贵的湿实验。现有自动注释方法多聚焦于蛋白质功能预测,利用序列、三维结构或蛋白家族信息。本文提出GoBERT,通过融合基因本体(Gene Ontology)图结构与BERT模型,揭示基因功能间的深层关联。设计两种预训练任务:邻域预测(自监督多标签分类)捕捉显性功能关系;指定掩码恢复任务挖掘隐性模式。预训练后的GoBERT可基于已知功能注释,预测各类基因及基因产物的新功能。大量实验、生物案例分析与消融研究验证了其优越性。
原文摘要 · Abstract (English)
Exploring the functions of genes and gene products is crucial to a wide range of fields, including medical research, evolutionary biology, and environmental science. However, discovering new functions largely relies on expensive and exhaustive wet lab experiments. Existing methods of automatic function annotation or prediction mainly focus on protein function prediction with sequence, 3D-structures or protein family information. In this study, we propose to tackle the gene function prediction problem by exploring Gene Ontology graph and annotation with BERT (GoBERT) to decipher the underlying relationships among gene functions. Our proposed novel function prediction task utilizes existing functions as inputs and generalizes the function prediction to gene and gene products. Specifically, two pre-train tasks are designed to jointly train GoBERT to capture both explicit and implicit relations of functions. Neighborhood prediction is a self-supervised multi-label classification task that captures the explicit function relations. Specified masking and recovering task helps GoBERT in finding implicit patterns among functions. The pre-trained GoBERT possess the ability to predict novel functions for various gene and gene products based on known functional annotations. Extensive experiments, biological case studies, and ablation studies are conducted to demonstrate the superiority of our proposed GoBERT.
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