Deep learning model for protein multi-label subcellular localization and function prediction based on multi-task collaborative training.

The functional study of proteins is a critical task in modern biology, playing a pivotal role in understanding the mechanisms of pathogenesis, developing new drugs, and discovering novel drug targets. However, existing computational models for subcellular localization face significant challenges, such as reliance on known Gene Ontology (GO) annotation databases or overlooking the relationship between GO annotations and subcellular localization. To address these issues, we propose DeepMTC, an end-to-end deep learning-based multi-task collaborative training model. DeepMTC integrates the interrelationship between subcellular localization and the functional annotation of proteins, leveraging multi-task collaborative training to eliminate dependence on known GO databases. This strategy gives DeepMTC a distinct advantage in predicting newly discovered proteins without prior functional annotations. First, DeepMTC leverages pre-trained language model with high accuracy to obtain the 3D structure and sequence features of proteins. Additionally, it employs a graph transformer module to encode protein sequence features, addressing the problem of long-range dependencies in graph neural networks. Finally, DeepMTC uses a functional cross-attention mechanism to efficiently combine upstream learned functional features to perform the subcellular localization task. The experimental results demonstrate that DeepMTC outperforms state-of-the-art models in both protein function prediction and subcellular localization. Moreover, interpretability experiments revealed that DeepMTC can accurately identify the key residues and functional domains of proteins, confirming its superior performance. The code and dataset of DeepMTC are freely available at https://github.com/ghli16/DeepMTC.

Node-adaptive graph Transformer with structural encoding for accurate and robust lncRNA-disease association prediction.

BACKGROUND: Long noncoding RNAs (lncRNAs) are integral to a plethora of critical cellular biological processes, including the regulation of gene expression, cell differentiation, and the development of tumors and cancers. Predicting the relationships between lncRNAs and diseases can contribute to a better understanding of the pathogenic mechanisms of disease and provide strong support for the development of advanced treatment methods. RESULTS: Therefore, we present an innovative Node-Adaptive Graph Transformer model for predicting unknown LncRNA-Disease Associations, named NAGTLDA. First, we utilize the node-adaptive feature smoothing (NAFS) method to learn the local feature information of nodes and encode the structural information of the fusion similarity network of diseases and lncRNAs using Structural Deep Network Embedding (SDNE). Next, the Transformer module is used to capture potential association information between the network nodes. Finally, we employ a Transformer module with two multi-headed attention layers for learning global-level embedding fusion. Network structure coding is added as the structural inductive bias of the network to compensate for the missing message-passing mechanism in Transformer. NAGTLDA achieved an average AUC of 0.9531 and AUPR of 0.9537 significantly higher than state-of-the-art methods in 5-fold cross validation. We perform case studies on 4 diseases; 55 out of 60 associations between lncRNAs and diseases have been validated in the literatures. The results demonstrate the enormous potential of the graph Transformer structure to incorporate graph structural information for uncovering lncRNA-disease unknown correlations. CONCLUSIONS: Our proposed NAGTLDA model can serve as a highly efficient computational method for predicting biological information associations.

Identifying virulence factors using graph transformer autoencoder with ESMFold-predicted structures.

With the increasing resistance of bacterial pathogens to conventional antibiotics, antivirulence strategies targeting virulence factors (VFs) have become an effective new therapy for the treatment of pathogenic bacterial infections. Therefore, the identification and prediction of VFs can provide ideal candidate targets for the implementation of antivirulence strategies in treating infections caused by pathogenic bacteria. Currently, the existing computational models predominantly rely on the amino acid sequences of virulence proteins while overlooking structural information. Here, we propose a novel graph transformer autoencoder for VF identification (GTAE-VF), which utilizes ESMFold-predicted 3D structures and converts the VF identification problem into a graph-level prediction task. In an encoder-decoder framework, GTAE-VF adaptively learns both local and global information by integrating a graph convolutional network and a transformer to implement all-pair message passing, which can better capture long-range correlations and potential relationships. Extensive experiments on an independent test dataset demonstrate that GTAE-VF achieves reliable and robust prediction accuracy with an AUC of 0.963, which is consistently better than that of other structure-based and sequence-based approaches. We believe that GTAE-VF has the potential to emerge as a valuable tool for assessing VFs and devising antivirulence strategies.