DeepGDel: Deep Learning-Based Gene Deletion Prediction Framework for Growth-Coupled Production in Genome-Scale Metabolic Models

In genome-scale constraint-based metabolic models, gene deletion strategies are crucial for achieving growth-coupled production, where cell growth and target metabolite production are simultaneously achieved. While computational methods for calculating gene deletions have been widely explored and have contributed to gene deletion strategy databases, current approaches remain computationally demanding and have yet to fully leverage emerging data-driven paradigms, such as machine learning, for more efficient strain design. Therefore, it is necessary to propose a fundamental framework for this objective. In this study, we first formulate the problem of gene deletion strategy prediction and then propose a framework for predicting gene deletion strategies for growth-coupled production in genome-scale metabolic models. The proposed framework leverages deep learning algorithms to learn and integrate sequential gene and metabolite data representation, enabling the automatic gene deletion strategy prediction. Computational experiment results demonstrate the feasibility of the proposed framework, showing substantial improvements over baseline methods. Specifically, the proposed framework achieves a 14.69%, 22.52%, and 13.03% increase in overall accuracy across three metabolic models of different scales under study, while maintaining balanced precision and recall in predicting gene deletion statuses.