GraphNABP: Identifying nucleic acid-binding proteins with protein graphs and protein language models.

The computational identification of nucleic acid-binding proteins (NABP) is of great significance for understanding the mechanisms of these biological activities and drug discovery. Although a bunch of sequence-based methods have been proposed to predict NABP and achieved promising performance, the structure information is often overlooked. On the other hand, the power of popular protein language models (pLM) has seldom been harnessed for predicting NABPs. In this study, we propose a novel framework called GraphNABP, to predict NABP by integrating sequence and predicted 3D structure information. Specifically, sequence embeddings and protein molecular graphs were first obtained from ProtT5 protein language model and predicted 3D structures, respectively. Then, graph attention (GAT) and bidirectional long short-term memory (BiLSTM) neural networks were used to enhance feature representations. Finally, a fully connected layer is used to predict NABPs. To the best of our knowledge, this is the first time to integrate AlphaFold and protein language models for the prediction of NABPs. The performances on multiple independent test sets indicate that GraphNABP outperforms other state-of-the-art methods. Our results demonstrate the effectiveness of pLM embeddings and structural information for NABP prediction. The codes and data used in this study are available at https://github.com/lixiangli01/GraphNABP.

NeuroPpred-SHE: An interpretable neuropeptides prediction model based on selected features from hand-crafted features and embeddings of T5 model.

Neuropeptides are the most ubiquitous neurotransmitters in the immune system, regulating various biological processes. Neuropeptides play a significant role for the discovery of new drugs and targets for nervous system disorders. Traditional experimental methods for identifying neuropeptides are time-consuming and costly. Although several computational methods have been developed to predict the neuropeptides, the accuracy is still not satisfactory due to the representability of the extracted features. In this work, we propose an efficient and interpretable model, NeuroPpred-SHE, for predicting neuropeptides by selecting the optimal feature subset from both hand-crafted features and embeddings of a protein language model. Specially, we first employed a pre-trained T5 protein language model to extract embedding features and twelve other encoding methods to extract hand-crafted features from peptide sequences, respectively. Secondly, we fused both embedding features and hand-crafted features to enhance the feature representability. Thirdly, we utilized random forest (RF), Max-Relevance and Min-Redundancy (mRMR) and eXtreme Gradient Boosting (XGBoost) methods to select the optimal feature subset from the fused features. Finally, we employed five machine learning methods (GBDT, XGBoost, SVM, MLP, and LightGBM) to build the models. Our results show that the model based on GBDT achieves the best performance. Furthermore, our final model was compared with other state-of-the-art methods on an independent test set, the results indicate that our model achieves an AUROC of 97.8 % which is higher than all the other state-of-the-art predictors. Our model is available at: https://github.com/wenjean/NeuroPpred-SHE.

Protein-DNA interface hotspots prediction based on fusion features of embeddings of protein language model and handcrafted features.

The identification of hotspot residues at the protein-DNA binding interfaces plays a crucial role in various aspects such as drug discovery and disease treatment. Although experimental methods such as alanine scanning mutagenesis have been developed to determine the hotspot residues on protein-DNA interfaces, they are both inefficient and costly. Therefore, it is highly necessary to develop efficient and accurate computational methods for predicting hotspot residues. Several computational methods have been developed, however, they are mainly based on hand-crafted features which may not be able to represent all the information of proteins. In this regard, we propose a model called PDH-EH, which utilizes fused features of embeddings extracted from a protein language model (PLM) and handcrafted features. After we extracted the total 1141 dimensional features, we used mRMR to select the optimal feature subset. Based on the optimal feature subset, several different learning algorithms such as Random Forest, Support Vector Machine, and XGBoost were used to build the models. The cross-validation results on the training dataset show that the model built by using Random Forest achieves the highest AUROC. Further evaluation on the independent test set shows that our model outperforms the existing state-of-the-art models. Moreover, the effectiveness and interpretability of embeddings extracted from PLM were demonstrated in our analysis. The codes and datasets used in this study are available at: https://github.com/lixiangli01/PDH-EH.