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Purpose: Sequenced Protein–Protein Interaction (PPI) prediction represents a pivotal area of study in biology, playing a crucial role in elucidating the mechanistic underpinnings of diseases and facilitating the design of novel therapeutic interventions. Conventional methods for extracting features through experimental processes have proven to be both costly and exceedingly complex. In light of these challenges, the scientific community has turned to computational approaches, particularly those grounded in deep learning methodologies. Despite the progress achieved by current deep learning technologies, their effectiveness diminishes when applied to larger, unfamiliar datasets. Results: In this study, the paper introduces a novel deep learning framework, termed DL-PPI, for predicting PPIs based on sequence data. The proposed framework comprises two key components aimed at improving the accuracy of feature extraction from individual protein sequences and capturing relationships between proteins in unfamiliar datasets. 1. Protein Node Feature Extraction Module: To enhance the accuracy of feature extraction from individual protein sequences and facilitate the understanding of relationships between proteins in unknown datasets, the paper devised a novel protein node feature extraction module utilizing the Inception method. This module efficiently captures relevant patterns and representations within protein sequences, enabling more informative feature extraction. 2. Feature-Relational Reasoning Network (FRN): In the Global Feature Extraction module of our model, the paper developed a novel FRN that leveraged Graph Neural Networks to determine interactions between pairs of input proteins. The FRN effectively captures the underlying relational information between proteins, contributing to improved PPI predictions. DL-PPI framework demonstrates state-of-the-art performance in the realm of sequence-based PPI prediction. [ABSTRACT FROM AUTHOR]

Background: The Drug–Target Interaction (DTI) prediction uses a drug molecule and a protein sequence as inputs to predict the binding affinity value. In recent years, deep learning-based models have gotten more attention. These methods have two modules: the feature extraction module and the task prediction module. In most deep learning-based approaches, a simple task prediction loss (i.e., categorical cross entropy for the classification task and mean squared error for the regression task) is used to learn the model. In machine learning, contrastive-based loss functions are developed to learn more discriminative feature space. In a deep learning-based model, extracting more discriminative feature space leads to performance improvement for the task prediction module. Results: In this paper, we have used multimodal knowledge as input and proposed an attention-based fusion technique to combine this knowledge. Also, we investigate how utilizing contrastive loss function along the task prediction loss could help the approach to learn a more powerful model. Four contrastive loss functions are considered: (1) max-margin contrastive loss function, (2) triplet loss function, (3) Multi-class N-pair Loss Objective, and (4) NT-Xent loss function. The proposed model is evaluated using four well-known datasets: Wang et al. dataset, Luo's dataset, Davis, and KIBA datasets. Conclusions: Accordingly, after reviewing the state-of-the-art methods, we developed a multimodal feature extraction network by combining protein sequences and drug molecules, along with protein–protein interaction networks and drug–drug interaction networks. The results show it performs significantly better than the comparable state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

LncRNA–protein interactions are ubiquitous in organisms and play a crucial role in a variety of biological processes and complex diseases. Many computational methods have been reported for lncRNA–protein interaction prediction. However, the experimental techniques to detect lncRNA–protein interactions are laborious and time-consuming. Therefore, to address this challenge, this paper proposes a reweighting boosting feature selection (RBFS) method model to select key features. Specially, a reweighted apporach can adjust the contribution of each observational samples to learning model fitting; let higher weights are given more influence samples than those with lower weights. Feature selection with boosting can efficiently rank to iterate over important features to obtain the optimal feature subset. Besides, in the experiments, the RBFS method is applied to the prediction of lncRNA–protein interactions. The experimental results demonstrate that our method achieves higher accuracy and less redundancy with fewer features. [ABSTRACT FROM AUTHOR]

Protein structure prediction (PSP) has achieved significant progress lately via prediction of inter-residue distances using deep learning models and exploitation of the predictions during conformational search. In this context, prediction of large inter-residue distances and also prediction of distances between residues separated largely in the protein sequence remain challenging. To deal with these challenges, state-of-the-art inter-residue distance prediction algorithms have used large sets of coevolutionary and non-coevolutionary features. In this paper, we argue that the more the types of features used, the more the kinds of noises introduced and then the deep learning model has to overcome the noises to improve the accuracy of the predictions. Also, multiple features capturing similar underlying characteristics might not necessarily have significantly better cumulative effect. So we scrutinise the feature space to reduce the types of features to be used, but at the same time, we strive to improve the prediction accuracy. Consequently, for inter-residue real distance prediction, in this paper, we propose a deep learning model named scrutinised distance predictor (SDP), which uses only 2 coevolutionary and 3 non-coevolutionary features. On several sets of benchmark proteins, our proposed SDP method improves mean Local Distance Different Test (LDDT) scores at least by 10% over existing state-of-the-art methods. The SDP program along with its data is available from the website https://gitlab.com/mahnewton/sdp. [ABSTRACT FROM AUTHOR]

Anticancer peptides (ACPs) are bioactive peptides with antitumor activity and have become the most promising drugs in the treatment of cancer. Therefore, the accurate prediction of ACPs is of great significance to the research of cancer diseases. In the paper, we developed a more efficient prediction model called ACP_MS. Firstly, the monoMonoKGap method is used to extract the characteristic of anticancer peptide sequences and form the digital features. Then, the AdaBoost model is used to select the most discriminating features from the digital features. Finally, a stochastic gradient descent algorithm is introduced to identify anticancer peptide sequences. We adopt 7-fold cross-validation and independent test set validation, and the final accuracy of the main dataset reached 92.653% and 91.597%, respectively. The accuracy of the alternate dataset reached 98.678% and 98.317%, respectively. Compared with other advanced prediction models, the ACP_MS model improves the identification ability of anticancer peptide sequences. The data of this model can be downloaded from the public website for free https://github.com/Zhoucaimao1998/Zc [ABSTRACT FROM AUTHOR]

Testing the significance of predictors in a regression model is one of the most important topics in statistics. This problem is especially difficult without any parametric assumptions on the data. This paper aims to test the null hypothesis that given confounding variables Z, X does not significantly contribute to the prediction of Y under the model-free setting, where X and Z are possibly high dimensional. We propose a general framework that first fits nonparametric machine learning regression algorithms on Y|ZY|Z and Y|(X,Z)Y|(X,Z), then compares the prediction power of the two models. The proposed method allows us to leverage the strength of the most powerful regression algorithms developed in the modern machine learning community. The P value for the test can be easily obtained by permutation. In simulations, we find that the proposed method is more powerful compared to existing methods. The proposed method allows us to draw biologically meaningful conclusions from two gene expression data analyses without strong distributional assumptions: 1) testing the prediction power of sequencing RNA for the proteins in cellular indexing of transcriptomes and epitopes by sequencing data and 2) identification of spatially variable genes in spatially resolved transcriptomics data. [ABSTRACT FROM AUTHOR]

Background: Drug–target interaction (DTI) prediction plays a crucial role in drug discovery. Although the advanced deep learning has shown promising results in predicting DTIs, it still needs improvements in two aspects: (1) encoding method, in which the existing encoding method, character encoding, overlooks chemical textual information of atoms with multiple characters and chemical functional groups; as well as (2) the architecture of deep model, which should focus on multiple chemical patterns in drug and target representations. Results: In this paper, we propose a multi-granularity multi-scaled self-attention (SAN) model by alleviating the above problems. Specifically, in process of encoding, we investigate a segmentation method for drug and protein sequences and then label the segmented groups as the multi-granularity representations. Moreover, in order to enhance the various local patterns in these multi-granularity representations, a multi-scaled SAN is built and exploited to generate deep representations of drugs and targets. Finally, our proposed model predicts DTIs based on the fusion of these deep representations. Our proposed model is evaluated on two benchmark datasets, KIBA and Davis. The experimental results reveal that our proposed model yields better prediction accuracy than strong baseline models. Conclusion: Our proposed multi-granularity encoding method and multi-scaled SAN model improve DTI prediction by encoding the chemical textual information of drugs and targets and extracting their various local patterns, respectively. [ABSTRACT FROM AUTHOR]

Background: Protein–protein interaction (PPI) plays an important role in regulating cells and signals. Despite the ongoing efforts of the bioassay group, continued incomplete data limits our ability to understand the molecular roots of human disease. Therefore, it is urgent to develop a computational method to predict PPIs from the perspective of molecular system. Methods: In this paper, a highly efficient computational model, MTV-PPI, is proposed for PPI prediction based on a heterogeneous molecular network by learning inter-view protein sequences and intra-view interactions between molecules simultaneously. On the one hand, the inter-view feature is extracted from the protein sequence by k-mer method. On the other hand, we use a popular embedding method LINE to encode the heterogeneous molecular network to obtain the intra-view feature. Thus, the protein representation used in MTV-PPI is constructed by the aggregation of its inter-view feature and intra-view feature. Finally, random forest is integrated to predict potential PPIs. Results: To prove the effectiveness of MTV-PPI, we conduct extensive experiments on a collected heterogeneous molecular network with the accuracy of 86.55%, sensitivity of 82.49%, precision of 89.79%, AUC of 0.9301 and AUPR of 0.9308. Further comparison experiments are performed with various protein representations and classifiers to indicate the effectiveness of MTV-PPI in predicting PPIs based on a complex network. Conclusion: The achieved experimental results illustrate that MTV-PPI is a promising tool for PPI prediction, which may provide a new perspective for the future interactions prediction researches based on heterogeneous molecular network. [ABSTRACT FROM AUTHOR]

Background: Protein–protein interaction (PPI) plays an important role in regulating cells and signals. Despite the ongoing efforts of the bioassay group, continued incomplete data limits our ability to understand the molecular roots of human disease. Therefore, it is urgent to develop a computational method to predict PPIs from the perspective of molecular system. Methods: In this paper, a highly efficient computational model, MTV-PPI, is proposed for PPI prediction based on a heterogeneous molecular network by learning inter-view protein sequences and intra-view interactions between molecules simultaneously. On the one hand, the inter-view feature is extracted from the protein sequence by k-mer method. On the other hand, we use a popular embedding method LINE to encode the heterogeneous molecular network to obtain the intra-view feature. Thus, the protein representation used in MTV-PPI is constructed by the aggregation of its inter-view feature and intra-view feature. Finally, random forest is integrated to predict potential PPIs. Results: To prove the effectiveness of MTV-PPI, we conduct extensive experiments on a collected heterogeneous molecular network with the accuracy of 86.55%, sensitivity of 82.49%, precision of 89.79%, AUC of 0.9301 and AUPR of 0.9308. Further comparison experiments are performed with various protein representations and classifiers to indicate the effectiveness of MTV-PPI in predicting PPIs based on a complex network. Conclusion: The achieved experimental results illustrate that MTV-PPI is a promising tool for PPI prediction, which may provide a new perspective for the future interactions prediction researches based on heterogeneous molecular network. [ABSTRACT FROM AUTHOR]

Phage therapy has become one of the most promising alternatives to antibiotics in the treatment of bacterial diseases, and identifying phage-host interactions (PHIs) helps to understand the possible mechanism through which a phage infects bacteria to guide the development of phage therapy. Compared with wet experiments, computational methods of identifying PHIs can reduce costs and save time and are more effective and economic. In this paper, we propose a PHI prediction method with a generative adversarial network (GAN)-based data augmentation and sequence-based feature fusion (PHIAF). First, PHIAF applies a GAN-based data augmentation module, which generates pseudo PHIs to alleviate the data scarcity. Second, PHIAF fuses the features originated from DNA and protein sequences for better performance. Third, PHIAF utilizes an attention mechanism to consider different contributions of DNA/protein sequence-derived features, which also provides interpretability of the prediction model. In computational experiments, PHIAF outperforms other state-of-the-art PHI prediction methods when evaluated via 5-fold cross-validation (AUC and AUPR are 0.88 and 0.86, respectively). An ablation study shows that data augmentation, feature fusion and an attention mechanism are all beneficial to improve the prediction performance of PHIAF. Additionally, four new PHIs with the highest PHIAF score in the case study were verified by recent literature. In conclusion, PHIAF is a promising tool to accelerate the exploration of phage therapy. [ABSTRACT FROM AUTHOR]