Predicting the effects of cultivation condition on gene regulation in Escherichia coli by using deep learning

Cell's physiology is affected by cultivation conditions at varying degrees, including carbon sources and inorganic nutrients in growth medium, and the presence or absence of aeration. When examining the effects of cultivation conditions on the cell, the cell's transcriptional response is often examined first among other phenotypes (e.g., proteome and metabolome). In this regard, we developed DeepMGR, a deep learning model that predicts the effects of culture media on gene regulation in Escherichia coli. DeepMGR specifically classifies the direction of gene regulation (i.e., upregulation, no regulation, or downregulation) for an input gene in comparison with M9 minimal medium with glucose as a control condition. For this classification task, DeepMGR uses a feedforward neural network to process: i) DNA sequence of a target gene, ii) presence or absence of aeration and trace elements, and iii) concentration and structural information (SMILES) of up to ten nutrients. The complete DeepMGR showed accuracy of 0.867 and F1 score of 0.703 for a test set from the gold standard dataset. DeepMGR was further subjected to simulation studies for validation where regulation directions for groups of homologous genes were predicted, and the DeepMGR results were compared with the literature with focus on carbon sources that upregulate specific genes. DeepMGR will be useful for designing experiments to understand gene regulations, especially in the context of metabolic engineering.