POOE: predicting oomycete effectors based on a pre-trained large protein language model.

Oomycetes are fungus-like eukaryotic microorganisms which can cause catastrophic diseases in many plants. Successful infection of oomycetes depends highly on their effector proteins that are secreted into plant cells to subvert plant immunity. Thus, systematic identification of effectors from the oomycete proteomes remains an initial but crucial step in understanding plant-pathogen relationships. However, the number of experimentally identified oomycete effectors is still limited. Currently, only a few bioinformatics predictors exist to detect potential effectors, and their prediction performance needs to be improved. Here, we used the sequence embeddings from a pre-trained large protein language model (ProtTrans) as input and developed a support vector machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance with an area under the precision-recall curve of 0.804 (area under the receiver operating characteristic curve = 0.893, accuracy = 0.874, precision = 0.777, recall = 0.684, and specificity = 0.936) in the fivefold cross-validation, considerably outperforming various combinations of popular machine learning algorithms and other commonly used sequence encoding schemes. A similar prediction performance was also observed in the independent test. Compared with the existing oomycete effector prediction methods, POOE provided very competitive and promising performance, suggesting that ProtTrans effectively captures rich protein semantic information and dramatically improves the prediction task. We anticipate that POOE can accelerate the identification of oomycete effectors and provide new hints to systematically understand the functional roles of effectors in plant-pathogen interactions. The web server of POOE is freely accessible at http://zzdlab.com/pooe/index.php. The corresponding source codes and data sets are also available at https://github.com/zzdlabzm/POOE.IMPORTANCEIn this work, we use the sequence representations from a pre-trained large protein language model (ProtTrans) as input and develop a Support Vector Machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance in the independent test set, considerably outperforming existing oomycete effector prediction methods. We expect that this new bioinformatics tool will accelerate the identification of oomycete effectors and further guide the experimental efforts to interrogate the functional roles of effectors in plant-pathogen interaction.

AraPathogen2.0: An Improved Prediction of Plant-Pathogen Protein-Protein Interactions Empowered by the Natural Language Processing Technique.

Plant-pathogen protein-protein interactions (PPIs) play crucial roles in the arm race between plants and pathogens. Therefore, the identification of these interspecies PPIs is very important for the mechanistic understanding of pathogen infection and plant immunity. Computational prediction methods can complement experimental efforts, but their predictive performance still needs to be improved. Motivated by the rapid development of natural language processing and its successful applications in the field of protein bioinformatics, here we present an improved XGBoost-based plant-pathogen PPI predictor (i.e., AraPathogen2.0), in which sequence encodings from the pretrained protein language model ESM2 and Arabidopsis PPI network-related node representations from the graph embedding technique struc2vec are used as input. Stringent benchmark experiments showed that AraPathogen2.0 could achieve a better performance than its precedent version, especially for processing the test data set with novel proteins unseen in the training data.

Pre-trained protein language model sheds new light on the prediction of Arabidopsis protein-protein interactions.

BACKGROUND: Protein-protein interactions (PPIs) are heavily involved in many biological processes. Consequently, the identification of PPIs in the model plant Arabidopsis is of great significance to deeply understand plant growth and development, and then to promote the basic research of crop improvement. Although many experimental Arabidopsis PPIs have been determined currently, the known interactomic data of Arabidopsis is far from complete. In this context, developing effective machine learning models from existing PPI data to predict unknown Arabidopsis PPIs conveniently and rapidly is still urgently needed. RESULTS: We used a large-scale pre-trained protein language model (pLM) called ESM-1b to convert protein sequences into high-dimensional vectors and then used them as the input of multilayer perceptron (MLP). To avoid the performance overestimation frequently occurring in PPI prediction, we employed stringent datasets to train and evaluate the predictive model. The results showed that the combination of ESM-1b and MLP (i.e., ESMAraPPI) achieved more accurate performance than the predictive models inferred from other pLMs or baseline sequence encoding schemes. In particular, the proposed ESMAraPPI yielded an AUPR value of 0.810 when tested on an independent test set where both proteins in each protein pair are unseen in the training dataset, suggesting its strong generalization and extrapolating ability. Moreover, the proposed ESMAraPPI model performed better than several state-of-the-art generic or plant-specific PPI predictors. CONCLUSION: Protein sequence embeddings from the pre-trained model ESM-1b contain rich protein semantic information. By combining with the MLP algorithm, ESM-1b revealed excellent performance in predicting Arabidopsis PPIs. We anticipate that the proposed predictive model (ESMAraPPI) can serve as a very competitive tool to accelerate the identification of Arabidopsis interactome.