Liang Hong

Yang Tan, Ruilin Wang, Banghao Wu et al.

Enzyme engineering enables the modification of wild-type proteins to meet industrial and research demands by enhancing catalytic activity, stability, binding affinities, and other properties. The emergence of deep learning methods for protein modeling has demonstrated superior results at lower costs compared to traditional approaches such as directed evolution and rational design. In mutation effect prediction, the key to pre-training deep learning models lies in accurately interpreting the complex relationships among protein sequence, structure, and function. This study introduces a retrieval-enhanced protein language model for comprehensive analysis of native properties from sequence and local structural interactions, as well as evolutionary properties from retrieved homologous sequences. The state-of-the-art performance of the proposed ProtREM is validated on over 2 million mutants across 217 assays from an open benchmark (ProteinGym). We also conducted post-hoc analyses of the model's ability to improve the stability and binding affinity of a VHH antibody. Additionally, we designed 10 new mutants on a DNA polymerase and conducted wet-lab experiments to evaluate their enhanced activity at higher temperatures. Both in silico and experimental evaluations confirmed that our method provides reliable predictions of mutation effects, offering an auxiliary tool for biologists aiming to evolve existing enzymes. The implementation is publicly available at https://github.com/tyang816/ProtREM.

Bei Liu, Tieyun Qian, Bing Liu et al.

The wide spread of location-based social networks brings about a huge volume of user check-in data, which facilitates the recommendation of points of interest (POIs). Recent advances on distributed representation shed light on learning low dimensional dense vectors to alleviate the data sparsity problem. Current studies on representation learning for POI recommendation embed both users and POIs in a common latent space, and users' preference is inferred based on the distance/similarity between a user and a POI. Such an approach is not in accordance with the semantics of users and POIs as they are inherently different objects. In this paper, we present a novel spatiotemporal aware (STA) representation, which models the spatial and temporal information as \emph{a relationship connecting users and POIs}. Our model generalizes the recent advances in knowledge graph embedding. The basic idea is that the embedding of a $<$time, location$>$ pair corresponds to a translation from embeddings of users to POIs. Since the POI embedding should be close to the user embedding plus the relationship vector, the recommendation can be performed by selecting the top-\emph{k} POIs similar to the translated POI, which are all of the same type of objects. We conduct extensive experiments on two real-world datasets. The results demonstrate that our STA model achieves the state-of-the-art performance in terms of high recommendation accuracy, robustness to data sparsity and effectiveness in handling cold start problem.