In silico, in vitro, and in vivo machine learning in synthetic biology and metabolic engineering.

Among the main learning methods reviewed in this study and used in synthetic biology and metabolic engineering are supervised learning, reinforcement and active learning, and in vitro or in vivo learning. In the context of biosynthesis, supervised machine learning is being exploited to predict biological sequence activities, predict structures and engineer sequences, and optimize culture conditions. Active and reinforcement learning methods use training sets acquired through an iterative process generally involving experimental measurements. They are applied to design, engineer, and optimize metabolic pathways and bioprocesses. The nascent but promising developments with in vitro and in vivo learning comprise molecular circuits performing simple tasks such as pattern recognition and classification.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.