Prediction of Protein–Protein Interaction Sites Based on Stratified Attentional Mechanisms

Proteins are the basic substances that undertake human life activities, and they often perform their biological functions through interactions with other biological macromolecules, such as cell transmission and signal transduction. Predicting the interaction sites between proteins can deepen the understanding of the principle of protein interactions, but traditional experimental methods are time-consuming and labor-intensive. In this study, a new hierarchical attention network structure, named HANPPIS, by adding six effective features of protein sequence, position-specific scoring matrix (PSSM), secondary structure, pre-training vector, hydrophilic, and amino acid position, is proposed to predict protein–protein interaction (PPI) sites. The experiment proved that our model has obtained very effective results, which was better than the existing advanced calculation methods. More importantly, we used the double-layer attention mechanism to improve the interpretability of the model and to a certain extent solved the problem of the “black box” of deep neural networks, which can be used as a reference for location positioning on the biological level.

A Deep Learning and XGBoost-Based Method for Predicting Protein-Protein Interaction Sites

Knowledge about protein-protein interactions is beneficial in understanding cellular mechanisms. Protein-protein interactions are usually determined according to their protein-protein interaction sites. Due to the limitations of current techniques, it is still a challenging task to detect protein-protein interaction sites. In this article, we presented a method based on deep learning and XGBoost (called DeepPPISP-XGB) for predicting protein-protein interaction sites. The deep learning model served as a feature extractor to remove redundant information from protein sequences. The Extreme Gradient Boosting algorithm was used to construct a classifier for predicting protein-protein interaction sites. The DeepPPISP-XGB achieved the following results: area under the receiver operating characteristic curve of 0.681, a recall of 0.624, and area under the precision-recall curve of 0.339, being competitive with the state-of-the-art methods. We also validated the positive role of global features in predicting protein-protein interaction sites.

Modified naive Bayes classifier for classification of protein-protein interaction sites

The prediction of protein-protein interaction sites (PPIs) is a vital importance in biology for understanding the physical and functional interactions between molecules in living systems. There are several classification approaches for the prediction of PPI sites; the naïve Bayes classifier is one of the most popular candidates. But the ordinary naïve Bayes classifier is sensitive to unusual protein sequence profiling feature dataset and sometimes it gives ambiguous prediction results. To overcome this problem we have been modified the naïve Bayes classifier by radial basis function (RBF) kernel for the prediction of PPI sites. We investigate the performance of our proposed method compared with the popular classifiers like linear discriminant analysis (LDA), naïve Bayes classifier (NBC), support vector machine (SVM), AdaBoost and k-nearest neighbor (KNN) by the protein sequence profiling data analysis. The mNBC method showed sensitivity (86%), specificity (81%), accuracy (83%) and MCC (65%) for prediction of PPI sites.

DELPHI: accurate deep ensemble model for protein interaction sites prediction

Motivation Proteins usually perform their functions by interacting with other proteins, which is why accurately predicting protein–protein interaction (PPI) binding sites is a fundamental problem. Experimental methods are slow and expensive. Therefore, great efforts are being made towards increasing the performance of computational methods. Results We propose DEep Learning Prediction of Highly probable protein Interaction sites (DELPHI), a new sequence-based deep learning suite for PPI-binding sites prediction. DELPHI has an ensemble structure which combines a CNN and a RNN component with fine tuning technique. Three novel features, HSP, position information and ProtVec are used in addition to nine existing ones. We comprehensively compare DELPHI to nine state-of-the-art programmes on five datasets, and DELPHI outperforms the competing methods in all metrics even though its training dataset shares the least similarities with the testing datasets. In the most important metrics, AUPRC and MCC, it surpasses the second best programmes by as much as 18.5% and 27.7%, respectively. We also demonstrated that the improvement is essentially due to using the ensemble model and, especially, the three new features. Using DELPHI it is shown that there is a strong correlation with protein-binding residues (PBRs) and sites with strong evolutionary conservation. In addition, DELPHI’s predicted PBR sites closely match known data from Pfam. DELPHI is available as open-sourced standalone software and web server. Availability and implementation The DELPHI web server can be found at delphi.csd.uwo.ca/, with all datasets and results in this study. The trained models, the DELPHI standalone source code, and the feature computation pipeline are freely available at github.com/lucian-ilie/DELPHI. Supplementary information Supplementary data are available at Bioinformatics online.

ConvsPPIS: Identifying Protein-protein Interaction Sites by an Ensemble Convolutional Neural Network with Feature Graph

Background/Objective: Protein-protein interactions are essentials for most cellular processes and thus, unveiling how proteins interact with is a crucial question that can be better understood by recognizing which residues participate in the interaction. Although many computational approaches have been proposed to predict interface residues, their feature perspective and model learning ability are not enough to achieve ideal results. So, our objective is to improve the predictive performance under considering feature perspective and new learning algorithm. Method: In this study, we proposed an ensemble deep convolutional neural network, which explores the context and positional context of consecutive residues within a protein sub-sequence. Specifically, unlike the feature view of previous methods, ConvsPPIS uses evolutionary, physicochemical, and structural protein characteristics to construct their own feature graph respectively. After that, three independent deep convolutional neural networks are trained on each type of feature graph for learning the underlying pattern in sub-sequence. Lastly, we integrated those three deep networks into an ensemble predictor with leveraging complementary information of those features to predict potential interface residues. Results: Some comparative experiments have conducted through 10-fold cross-validation. The results indicated that ConvsPPIS achieved superior performance on DBv5-Sel dataset with an accuracy of 88%. Additional experiments on CAPRI-Alone dataset demonstrated ConvsPPIS has also better prediction performance. Conclusion: The ConvsPPIS method provided a new perspective to capture protein feature expression for identifying protein-protein interaction sites. The results proved the superiority of this method.

Developing Computational Model to Predict Protein-Protein Interaction Sites Based on the XGBoost Algorithm

The study of protein-protein interaction is of great biological significance, and the prediction of protein-protein interaction sites can promote the understanding of cell biological activity and will be helpful for drug development. However, uneven distribution between interaction and non-interaction sites is common because only a small number of protein interactions have been confirmed by experimental techniques, which greatly affects the predictive capability of computational methods. In this work, two imbalanced data processing strategies based on XGBoost algorithm were proposed to re-balance the original dataset from inherent relationship between positive and negative samples for the prediction of protein-protein interaction sites. Herein, a feature extraction method was applied to represent the protein interaction sites based on evolutionary conservatism of proteins, and the influence of overlapping regions of positive and negative samples was considered in prediction performance. Our method showed good prediction performance, such as prediction accuracy of 0.807 and MCC of 0.614, on an original dataset with 10,455 surface residues but only 2297 interface residues. Experimental results demonstrated the effectiveness of our XGBoost-based method.