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The heterologous expression of recombinant protein requires host cells, such as Escherichia coli, and the solubility of protein greatly affects the protein yield. A novel and highly accurate solubility predictor that concurrently improves the production yield and minimizes production cost, and that forecasts protein solubility in an E. coli expression system before the actual experimental work is highly sought. In this paper, EPSOL, a novel deep learning architecture for the prediction of protein solubility in an E. coli expression syst