arXiv:2504.06316q-bio.QMcs.LG2025-04

用图模型提升基因删除策略预测准确率,让微生物高效生产目标物质。

GraphGDel: Constructing and Learning Graph Representations of Genome-Scale Metabolic Models for Growth-Coupled Gene Deletion Prediction

  • 构建代谢网络图结构,融合基因代谢物序列数据进行深度学习。
  • 在三个模型上准确率比基线最高提升16.26%。
  • 适合代谢工程、合成生物学研究者参考使用。

在基因组规模的约束代谢模型中,基因删除策略对实现生长偶联生产至关重要,即细胞生长与目标代谢物合成同步进行。尽管代谢模型具有天然网络特性,现有计算方法主要依赖序列数据,缺乏能捕捉其复杂关系的图表示,且相应的图构造与学习框架尚未充分探索。为此,本文提出双管齐下的解决方案:首先建立从约束代谢模型系统构建图表示的流程;其次开发一种深度学习框架,将图表示与基因、代谢物序列数据结合,预测生长偶联基因删除策略。在三个代谢模型上,该方法整体准确率分别较深度前馈神经网络基线提升14.04%、16.26%、13.18%,较序列学习基线提升6.17%、4.96%、5.31%,较拓扑感知图聚合基线提升5.10%、4.36%、4.70%。源代码与示例数据集见:https://github.com/MetNetComp/GraphGDel。

原文摘要 · Abstract (English)

In genome-scale constraint-based metabolic models, gene deletion strategies are essential for achieving growth-coupled production, where cell growth and target metabolite synthesis occur simultaneously. Despite the inherently networked nature of genome-scale metabolic models, existing computational approaches rely primarily on sequential data and lack graph representations that capture their complex relationships, as both well-defined graph constructions and learning frameworks capable of exploiting them remain largely unexplored. To address this gap, we present a twofold solution. First, we introduce a systematic pipeline for constructing graph representations from constraint-based metabolic models. Second, we develop a deep learning framework that integrates these graph representations with gene and metabolite sequence data to predict growth-coupled gene deletion strategies. Across three metabolic models, our approach consistently outperforms established baselines, with improvements in overall accuracy of 14.04%, 16.26%, and 13.18% over a deep feedforward neural network baseline, 6.17%, 4.96%, and 5.31% over a sequence-learning baseline, and 5.10%, 4.36%, and 4.70% over a topology-aware graph aggregation baseline on the same metabolite graph, respectively. The source code and example datasets are available at: https://github.com/MetNetComp/GraphGDel.

代谢建模图神经网络基因编辑合成生物学

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