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Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 β-lactamase and identified variants with improved ampicillin resistance with high success rates.

 

Iterating machine learning with robotic experimentation uncovered higher-yielding conditions for a common coupling reaction. 

Taxonomies are fundamental to many real-world applications in various domains, serving as structural representations of knowledge. To deal with the increasing volume of new concepts needed to be organized as taxonomies, researchers turn to automatically completion of an existing taxonomy with new concepts. In this paper, we propose TaxoEnrich, a new taxonomy completion framework, which effectively leverages both semantic features and structural information in the existing taxonomy and offers a better representation of candidate position to boost the performance of taxonomy completion. Specifically, TaxoEnrich consists of four components: (1) taxonomy-contextualized embedding which incorporates both semantic meanings of concept and taxonomic relations based on powerful pretrained language models; (2) a taxonomy-aware sequential encoder which learns candidate position representations by encoding the structural information of taxonomy; (3) a query-aware sibling encoder which adaptively aggregates candidate siblings to augment candidate position representations based on their importance to the query-position matching; (4) a query-position matching model which extends existing work with our new candidate position representations. Extensive experiments on four large real-world datasets from different domains show that TaxoEnrich achieves the best performance among all evaluation metrics and outperforms previous state-of-the-art methods by a large margin.