Integrated convolution and self-attention for improving peptide toxicity prediction.

MOTIVATION: Peptides are promising agents for the treatment of a variety of diseases due to their specificity and efficacy. However, the development of peptide-based drugs is often hindered by the potential toxicity of peptides, which poses a significant barrier to their clinical application. Traditional experimental methods for evaluating peptide toxicity are time-consuming and costly, making the development process inefficient. Therefore, there is an urgent need for computational tools specifically designed to predict peptide toxicity accurately and rapidly, facilitating the identification of safe peptide candidates for drug development. RESULTS: We provide here a novel computational approach, CAPTP, which leverages the power of convolutional and self-attention to enhance the prediction of peptide toxicity from amino acid sequences. CAPTP demonstrates outstanding performance, achieving a Matthews correlation coefficient of approximately 0.82 in both cross-validation settings and on independent test datasets. This performance surpasses that of existing state-of-the-art peptide toxicity predictors. Importantly, CAPTP maintains its robustness and generalizability even when dealing with data imbalances. Further analysis by CAPTP reveals that certain sequential patterns, particularly in the head and central regions of peptides, are crucial in determining their toxicity. This insight can significantly inform and guide the design of safer peptide drugs. AVAILABILITY AND IMPLEMENTATION: The source code for CAPTP is freely available at https://github.com/jiaoshihu/CAPTP.

Adaptive learning embedding features to improve the predictive performance of SARS-CoV-2 phosphorylation sites.

MOTIVATION: The rapid and extensive transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health emergency, affecting millions of people and causing an immense socioeconomic impact. The identification of SARS-CoV-2 phosphorylation sites plays an important role in unraveling the complex molecular mechanisms behind infection and the resulting alterations in host cell pathways. However, currently available prediction tools for identifying these sites lack accuracy and efficiency. RESULTS: In this study, we presented a comprehensive biological function analysis of SARS-CoV-2 infection in a clonal human lung epithelial A549 cell, revealing dramatic changes in protein phosphorylation pathways in host cells. Moreover, a novel deep learning predictor called PSPred-ALE is specifically designed to identify phosphorylation sites in human host cells that are infected with SARS-CoV-2. The key idea of PSPred-ALE lies in the use of a self-adaptive learning embedding algorithm, which enables the automatic extraction of context sequential features from protein sequences. In addition, the tool uses multihead attention module that enables the capturing of global information, further improving the accuracy of predictions. Comparative analysis of features demonstrated that the self-adaptive learning embedding features are superior to hand-crafted statistical features in capturing discriminative sequence information. Benchmarking comparison shows that PSPred-ALE outperforms the state-of-the-art prediction tools and achieves robust performance. Therefore, the proposed model can effectively identify phosphorylation sites assistant the biomedical scientists in understanding the mechanism of phosphorylation in SARS-CoV-2 infection. AVAILABILITY AND IMPLEMENTATION: PSPred-ALE is available at https://github.com/jiaoshihu/PSPred-ALE and Zenodo (https://doi.org/10.5281/zenodo.8330277).

Sequence-Based Prediction with Feature Representation Learning and Biological Function Analysis of Channel Proteins.

BACKGROUND: Channel proteins are proteins that can transport molecules past the plasma membrane through free diffusion movement. Due to the cost of labor and experimental methods, developing a tool to identify channel proteins is necessary for biological research on channel proteins. METHODS: 17 feature coding methods and four machine learning classifiers to generate 68-dimensional data probability features. Then, the two-step feature selection strategy was used to optimize the features, and the final prediction Model M16-LGBM (light gradient boosting machine) was obtained on the 16-dimensional optimal feature vector. RESULTS: A new predictor, CAPs-LGBM, was proposed to identify the channel proteins effectively. CONCLUSIONS: CAPs-LGBM is the first channel protein machine learning predictor was used to construct the final prediction model based on protein primary sequences. The classifier performed well in the training and test sets.

Identification of plant vacuole proteins by exploiting deep representation learning features.

Plant vacuoles are the most important organelles for plant growth, development, and defense, and they play an important role in many types of stress responses. An important function of vacuole proteins is the transport of various classes of amino acids, ions, sugars, and other molecules. Accurate identification of vacuole proteins is crucial for revealing their biological functions. Several automatic and rapid computational tools have been proposed for the subcellular localization of proteins. Regrettably, they are not specific for the identification of plant vacuole proteins. To the best of our knowledge, there is only one computational software specifically trained for plant vacuolar proteins. Although its accuracy is acceptable, the prediction performance and stability of this method in practical applications can still be improved. Hence, in this study, a new predictor named iPVP-DRLF was developed to identify plant vacuole proteins specifically and effectively. This prediction software is designed using the light gradient boosting machine (LGBM) algorithm and hybrid features composed of classic sequence features and deep representation learning features. iPVP-DRLF achieved fivefold cross-validation and independent test accuracy values of 88.25 % and 87.16 %, respectively, both outperforming previous state-of-the-art predictors. Moreover, the blind dataset test results also showed that the performance of iPVP-DRLF was significantly better than the existing tools. The results of comparative experiments confirmed that deep representation learning features have an advantage over other classic sequence features in the identification of plant vacuole proteins. We believe that iPVP-DRLF would serve as an effective computational technique for plant vacuole protein prediction and facilitate related future research. The online server is freely accessible at https://lab.malab.cn/~acy/iPVP-DRLF. In addition, the source code and datasets are also accessible at https://github.com/jiaoshihu/iPVP-DRLF.

ATGPred-FL: sequence-based prediction of autophagy proteins with feature representation learning.

Autophagy plays an important role in biological evolution and is regulated by many autophagy proteins. Accurate identification of autophagy proteins is crucially important to reveal their biological functions. Due to the expense and labor cost of experimental methods, it is urgent to develop automated, accurate and reliable sequence-based computational tools to enable the identification of novel autophagy proteins among numerous proteins and peptides. For this purpose, a new predictor named ATGPred-FL was proposed for the efficient identification of autophagy proteins. We investigated various sequence-based feature descriptors and adopted the feature learning method to generate corresponding, more informative probability features. Then, a two-step feature selection strategy based on accuracy was utilized to remove irrelevant and redundant features, leading to the most discriminative 14-dimensional feature set. The final predictor was built using a support vector machine classifier, which performed favorably on both the training and testing sets with accuracy values of 94.40% and 90.50%, respectively. ATGPred-FL is the first ATG machine learning predictor based on protein primary sequences. We envision that ATGPred-FL will be an effective and useful tool for autophagy protein identification, and it is available for free at http://lab.malab.cn/~acy/ATGPred-FL , the source code and datasets are accessible at https://github.com/jiaoshihu/ATGPred .

The Characterization of Structure and Prediction for Aquaporin in Tumour Progression by Machine Learning.

Recurrence and new cases of cancer constitute a challenging human health problem. Aquaporins (AQPs) can be expressed in many types of tumours, including the brain, breast, pancreas, colon, skin, ovaries, and lungs, and the histological grade of cancer is positively correlated with AQP expression. Therefore, the identification of aquaporins is an area to explore. Computational tools play an important role in aquaporin identification. In this research, we propose reliable, accurate and automated sequence predictor iAQPs-RF to identify AQPs. In this study, the feature extraction method was 188D (global protein sequence descriptor, GPSD). Six common classifiers, including random forest (RF), NaiveBayes (NB), support vector machine (SVM), XGBoost, logistic regression (LR) and decision tree (DT), were used for AQP classification. The classification results show that the random forest (RF) algorithm is the most suitable machine learning algorithm, and the accuracy was 97.689%. Analysis of Variance (ANOVA) was used to analyse these characteristics. Feature rank based on the ANOVA method and IFS strategy was applied to search for the optimal features. The classification results suggest that the 26th feature (neutral/hydrophobic) and 21st feature (hydrophobic) are the two most powerful and informative features that distinguish AQPs from non-AQPs. Previous studies reported that plasma membrane proteins have hydrophobic characteristics. Aquaporin subcellular localization prediction showed that all aquaporins were plasma membrane proteins with highly conserved transmembrane structures. In addition, the 3D structure of aquaporins was consistent with the localization results. Therefore, these studies confirmed that aquaporins possess hydrophobic properties. Although aquaporins are highly conserved transmembrane structures, the phylogenetic tree shows the diversity of aquaporins during evolution. The PCA showed that positive and negative samples were well separated by 54D features, indicating that the 54D feature can effectively classify aquaporins. The online prediction server is accessible at http://lab.malab.cn/∼acy/iAQP.

iTTCA-RF: a random forest predictor for tumor T cell antigens.

BACKGROUND: Cancer is one of the most serious diseases threatening human health. Cancer immunotherapy represents the most promising treatment strategy due to its high efficacy and selectivity and lower side effects compared with traditional treatment. The identification of tumor T cell antigens is one of the most important tasks for antitumor vaccines development and molecular function investigation. Although several machine learning predictors have been developed to identify tumor T cell antigen, more accurate tumor T cell antigen identification by existing methodology is still challenging. METHODS: In this study, we used a non-redundant dataset of 592 tumor T cell antigens (positive samples) and 393 tumor T cell antigens (negative samples). Four types feature encoding methods have been studied to build an efficient predictor, including amino acid composition, global protein sequence descriptors and grouped amino acid and peptide composition. To improve the feature representation ability of the hybrid features, we further employed a two-step feature selection technique to search for the optimal feature subset. The final prediction model was constructed using random forest algorithm. RESULTS: Finally, the top 263 informative features were selected to train the random forest classifier for detecting tumor T cell antigen peptides. iTTCA-RF provides satisfactory performance, with balanced accuracy, specificity and sensitivity values of 83.71%, 78.73% and 88.69% over tenfold cross-validation as well as 73.14%, 62.67% and 83.61% over independent tests, respectively. The online prediction server was freely accessible at http://lab.malab.cn/~acy/iTTCA . CONCLUSIONS: We have proven that the proposed predictor iTTCA-RF is superior to the other latest models, and will hopefully become an effective and useful tool for identifying tumor T cell antigens presented in the context of major histocompatibility complex class I.

CWLy-RF: A novel approach for identifying cell wall lyases based on random forest classifier.

Drug resistance of pathogenic bacteria has become increasingly serious due to the abuse of antibiotics in recent years. Researchers have found that cell wall lyases are effective antibacterial agents that can specifically recognize target bacteria and degrade bacterial peptidoglycan. Traditional wet experiments are usually expensive, time-consuming and laborious for the identification of lyases. Therefore, there is an urgent need to develop prediction tools based on computer methods to identify lyases quickly and accurately. In this paper, a new predictor, CWLy-RF, is proposed based on the random forest (RF) algorithm to identify cell wall lyases. In this method, we combined three features, namely, 400D, 188D and the composition of k-spaced amino acid group pairs, using mixed-feature representation methods. Afterward, we improved the feature representation ability with the selected top 100 features by using the information gain method and trained a predictive model using RF. The constructed prediction model is evaluated by using 10-fold cross-validation. The accuracy obtained was 96.09%, the AUC was 0.993, the MCC was 0.922, the sensitivity was 94.92%, and the specificity was 97.32%. We have proved that the proposed predictor CWLy-RF is superior to other latest models, and it will hopefully become an effective and useful tool for identifying lyases.

Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.

Identification of long noncoding RNAs with machine learning methods: a review.

Long noncoding RNAs (lncRNAs) are noncoding RNAs with a length greater than 200 nucleotides. Studies have shown that they play an important role in many life activities. Dozens of lncRNAs have been characterized to some extent, and they are reported to be related to the development of diseases in a variety of cells. However, the biological functions of most lncRNAs are currently still unclear. Therefore, accurately identifying and predicting lncRNAs would be helpful for research on their biological functions. Due to the disadvantages of high cost and high resource-intensiveness of experimental methods, scientists have developed numerous computational methods to identify and predict lncRNAs in recent years. In this paper, we systematically summarize the machine learning-based lncRNAs prediction tools from several perspectives, and discuss the challenges and prospects for the future work.