Accelerating the identification of the allergenic potential of plant proteins using a stacked ensemble-learning framework.

Plant-allergenic proteins (PAPs) have the potential to induce allergic reactions in certain individuals. While these proteins are generally innocuous for the majority of people, they can elicit an immune response in those with particular sensitivities. Thus, screening and prioritizing the allergenic potential of plant proteins is indispensable for the development of diagnostic tools, therapeutic interventions or medications to treat allergic reactions. However, investigating the allergenic potential of plant proteins based on experimental methods is costly and labour-intensive. Therefore, we develop StackPAP, a three-layer stacking ensemble framework for accurate large-scale identification of PAPs. In StackPAP, at the first layer, we conducted a comprehensive analysis of an extensive set of feature descriptors. Subsequently, we selected and fused five potential sequence-based feature descriptors, including amphiphilic pseudo-amino acid composition, dipeptide deviation from expected mean, amino acid composition, pseudo amino acid composition and dipeptide composition. Additionally, we applied an efficient genetic algorithm (GA-SAR) to determine informative feature sets. In the second layer, 12 powerful machine learning (ML) methods, in combination with all the informative feature sets, were employed to construct a pool of base classifiers. Finally, 13 potential base classifiers were selected using the GA-SAR method and combined to develop the final meta-classifier. Our experimental results revealed the promising prediction performance of StackPAP, with an accuracy, Matthew's correlation coefficient and AUC of 0.984, 0.969 and 0.993, respectively, as judged by the independent test dataset. In conclusion, both cross-validation and independent test results indicated the superior performance of StackPAP compared with several ML-based classifiers. To accelerate the identification of the allergenicity of plant proteins, we developed a user-friendly web server for StackPAP (https://pmlabqsar.pythonanywhere.com/StackPAP). We anticipate that StackPAP will be an efficient and useful tool for rapidly screening PAPs from a vast number of plant proteins.Communicated by Ramaswamy H. Sarma.

Deep-WET: a deep learning-based approach for predicting DNA-binding proteins using word embedding techniques with weighted features.

DNA-binding proteins (DBPs) play a significant role in all phases of genetic processes, including DNA recombination, repair, and modification. They are often utilized in drug discovery as fundamental elements of steroids, antibiotics, and anticancer drugs. Predicting them poses the most challenging task in proteomics research. Conventional experimental methods for DBP identification are costly and sometimes biased toward prediction. Therefore, developing powerful computational methods that can accurately and rapidly identify DBPs from sequence information is an urgent need. In this study, we propose a novel deep learning-based method called Deep-WET to accurately identify DBPs from primary sequence information. In Deep-WET, we employed three powerful feature encoding schemes containing Global Vectors, Word2Vec, and fastText to encode the protein sequence. Subsequently, these three features were sequentially combined and weighted using the weights obtained from the elements learned through the differential evolution (DE) algorithm. To enhance the predictive performance of Deep-WET, we applied the SHapley Additive exPlanations approach to remove irrelevant features. Finally, the optimal feature subset was input into convolutional neural networks to construct the Deep-WET predictor. Both cross-validation and independent tests indicated that Deep-WET achieved superior predictive performance compared to conventional machine learning classifiers. In addition, in extensive independent test, Deep-WET was effective and outperformed than several state-of-the-art methods for DBP prediction, with accuracy of 78.08%, MCC of 0.559, and AUC of 0.805. This superior performance shows that Deep-WET has a tremendous predictive capacity to predict DBPs. The web server of Deep-WET and curated datasets in this study are available at https://deepwet-dna.monarcatechnical.com/ . The proposed Deep-WET is anticipated to serve the community-wide effort for large-scale identification of potential DBPs.

Leveraging a meta-learning approach to advance the accuracy of Nav blocking peptides prediction.

The voltage-gated sodium (Nav) channel is a crucial molecular component responsible for initiating and propagating action potentials. While the α subunit, forming the channel pore, plays a central role in this function, the complete physiological function of Nav channels relies on crucial interactions between the α subunit and auxiliary proteins, known as protein-protein interactions (PPI). Nav blocking peptides (NaBPs) have been recognized as a promising and alternative therapeutic agent for pain and itch. Although traditional experimental methods can precisely determine the effect and activity of NaBPs, they remain time-consuming and costly. Hence, machine learning (ML)-based methods that are capable of accurately contributing in silico prediction of NaBPs are highly desirable. In this study, we develop an innovative meta-learning-based NaBP prediction method (MetaNaBP). MetaNaBP generates new feature representations by employing a wide range of sequence-based feature descriptors that cover multiple perspectives, in combination with powerful ML algorithms. Then, these feature representations were optimized to identify informative features using a two-step feature selection method. Finally, the selected informative features were applied to develop the final meta-predictor. To the best of our knowledge, MetaNaBP is the first meta-predictor for NaBP prediction. Experimental results demonstrated that MetaNaBP achieved an accuracy of 0.948 and a Matthews correlation coefficient of 0.898 over the independent test dataset, which were 5.79% and 11.76% higher than the existing method. In addition, the discriminative power of our feature representations surpassed that of conventional feature descriptors over both the training and independent test datasets. We anticipate that MetaNaBP will be exploited for the large-scale prediction and analysis of NaBPs to narrow down the potential NaBPs.

Review of Computational Methods and Database Sources for Predicting the Effects of Coding Frameshift Small Insertion and Deletion Variations.

Genetic variations (including substitutions, insertions, and deletions) exert a profound influence on DNA sequences. These variations are systematically classified as synonymous, nonsynonymous, and nonsense, each manifesting distinct effects on proteins. The implementation of high-throughput sequencing has significantly augmented our comprehension of the intricate interplay between gene variations and protein structure and function, as well as their ramifications in the context of diseases. Frameshift variations, particularly small insertions and deletions (indels), disrupt protein coding and are instrumental in disease pathogenesis. This review presents a succinct review of computational methods, databases, current challenges, and future directions in predicting the consequences of coding frameshift small indels variations. We analyzed the predictive efficacy, reliability, and utilization of computational methods and variant account, reliability, and utilization of database. Besides, we also compared the prediction methodologies on GOF/LOF pathogenic variation data. Addressing the challenges pertaining to prediction accuracy and cross-species generalizability, nascent technologies such as AI and deep learning harbor immense potential to enhance predictive capabilities. The importance of interdisciplinary research and collaboration cannot be overstated for devising effective diagnosis, treatment, and prevention strategies concerning diseases associated with coding frameshift indels variations.

StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERß antagonists.

The role of estrogen receptors (ERs) in breast cancer is of great importance in both clinical practice and scientific exploration. However, around 15-30% of those affected do not see benefits from the usual treatments owing to the innate resistance mechanisms, while 30-40% will gain resistance through treatments. In order to address this problem and facilitate community-wide efforts, machine learning (ML)-based approaches are considered one of the most cost-effective and large-scale identification methods. Herein, we propose a new SMILES-based stacked approach, termed StackER, for the accelerated and efficient identification of ERα and ERß inhibitors. In StackER, we first established an up-to-date dataset consisting of 1,996 and 1,207 compounds for ERα and ERß, respectively. Using the up-to-date dataset, StackER explored a wide range of different SMILES-based feature descriptors and ML algorithms in order to generate probabilistic features (PFs). Finally, the selected PFs derived from the two-step feature selection strategy were used for the development of an efficient stacked model. Both cross-validation and independent tests showed that StackER surpassed several conventional ML classifiers and the existing method in precisely predicting ERα and ERß inhibitors. Remarkably, StackER achieved MCC values of 0.829-0.847 and 0.712-0.786 in terms of the cross-validation and independent tests, respectively, which were 5.92-8.29 and 1.59-3.45% higher than the existing method. In addition, StackER was applied to determine useful features for being ERα and ERß inhibitors and identify FDA-approved drugs as potential ERα inhibitors in efforts to facilitate drug repurposing. This innovative stacked method is anticipated to facilitate community-wide efforts in efficiently narrowing down ER inhibitor screening.

MMPatho: Leveraging Multilevel Consensus and Evolutionary Information for Enhanced Missense Mutation Pathogenic Prediction.

Understanding the pathogenicity of missense mutation (MM) is essential for shed light on genetic diseases, gene functions, and individual variations. In this study, we propose a novel computational approach, called MMPatho, for enhancing missense mutation pathogenic prediction. First, we established a large-scale nonredundant MM benchmark data set based on the entire Ensembl database, complemented by a focused blind test set specifically for pathogenic GOF/LOF MM. Based on this data set, for each mutation, we utilized Ensembl VEP v104 and dbNSFP v4.1a to extract variant-level, amino acid-level, individuals' outputs, and genome-level features. Additionally, protein sequences were generated using ENSP identifiers with the Ensembl API, and then encoded. The mutant sites' ESM-1b and ProtTrans-T5 embeddings were subsequently extracted. Then, our model group (MMPatho) was developed by leveraging upon these efforts, which comprised ConsMM and EvoIndMM. To be specific, ConsMM employs individuals' outputs and XGBoost with SHAP explanation analysis, while EvoIndMM investigates the potential enhancement of predictive capability by incorporating evolutionary information from ESM-1b and ProtT5-XL-U50, large protein language embeddings. Through rigorous comparative experiments, both ConsMM and EvoIndMM were capable of achieving remarkable AUROC (0.9836 and 0.9854) and AUPR (0.9852 and 0.9902) values on the blind test set devoid of overlapping variations and proteins from the training data, thus highlighting the superiority of our computational approach in the prediction of MM pathogenicity. Our Web server, available at http://csbio.njust.edu.cn/bioinf/mmpatho/, allows researchers to predict the pathogenicity (alongside the reliability index score) of MMs using the ConsMM and EvoIndMM models and provides extensive annotations for user input. Additionally, the newly constructed benchmark data set and blind test set can be accessed via the data page of our web server.

Empirical comparison and analysis of machine learning-based approaches for druggable protein identification.

Efficiently and precisely identifying drug targets is crucial for developing and discovering potential medications. While conventional experimental approaches can accurately pinpoint these targets, they suffer from time constraints and are not easily adaptable to high-throughput processes. On the other hand, computational approaches, particularly those utilizing machine learning (ML), offer an efficient means to accelerate the prediction of druggable proteins based solely on their primary sequences. Recently, several state-of-the-art computational methods have been developed for predicting and analyzing druggable proteins. These computational methods showed high diversity in terms of benchmark datasets, feature extraction schemes, ML algorithms, evaluation strategies and webserver/software usability. Thus, our objective is to reexamine these computational approaches and conduct a comprehensive assessment of their strengths and weaknesses across multiple aspects. In this study, we deliver the first comprehensive survey regarding the state-of-the-art computational approaches for in silico prediction of druggable proteins. First, we provided information regarding the existing benchmark datasets and the types of ML methods employed. Second, we investigated the effectiveness of these computational methods in druggable protein identification for each benchmark dataset. Third, we summarized the important features used in this field and the existing webserver/software. Finally, we addressed the present constraints of the existing methods and offer valuable guidance to the scientific community in designing and developing novel prediction models. We anticipate that this comprehensive review will provide crucial information for the development of more accurate and efficient druggable protein predictors.

TIPred: a novel stacked ensemble approach for the accelerated discovery of tyrosinase inhibitory peptides.

BACKGROUND: Tyrosinase is an enzyme involved in melanin production in the skin. Several hyperpigmentation disorders involve the overproduction of melanin and instability of tyrosinase activity resulting in darker, discolored patches on the skin. Therefore, discovering tyrosinase inhibitory peptides (TIPs) is of great significance for basic research and clinical treatments. However, the identification of TIPs using experimental methods is generally cost-ineffective and time-consuming. RESULTS: Herein, a stacked ensemble learning approach, called TIPred, is proposed for the accurate and quick identification of TIPs by using sequence information. TIPred explored a comprehensive set of various baseline models derived from well-known machine learning (ML) algorithms and heterogeneous feature encoding schemes from multiple perspectives, such as chemical structure properties, physicochemical properties, and composition information. Subsequently, 130 baseline models were trained and optimized to create new probabilistic features. Finally, the feature selection approach was utilized to determine the optimal feature vector for developing TIPred. Both tenfold cross-validation and independent test methods were employed to assess the predictive capability of TIPred by using the stacking strategy. Experimental results showed that TIPred significantly outperformed the state-of-the-art method in terms of the independent test, with an accuracy of 0.923, MCC of 0.757 and an AUC of 0.977. CONCLUSIONS: The proposed TIPred approach could be a valuable tool for rapidly discovering novel TIPs and effectively identifying potential TIP candidates for follow-up experimental validation. Moreover, an online webserver of TIPred is publicly available at http://pmlabstack.pythonanywhere.com/TIPred .

TROLLOPE: A novel sequence-based stacked approach for the accelerated discovery of linear T-cell epitopes of hepatitis C virus.

Hepatitis C virus (HCV) infection is a concerning health issue that causes chronic liver diseases. Despite many successful therapeutic outcomes, no effective HCV vaccines are currently available. Focusing on T cell activity, the primary effector for HCV clearance, T cell epitopes of HCV (TCE-HCV) are considered promising elements to accelerate HCV vaccine efficacy. Thus, accurate and rapid identification of TCE-HCVs is recommended to obtain more efficient therapy for chronic HCV infection. In this study, a novel sequence-based stacked approach, termed TROLLOPE, is proposed to accurately identify TCE-HCVs from sequence information. Specifically, we employed 12 different sequence-based feature descriptors from heterogeneous perspectives, such as physicochemical properties, composition-transition-distribution information and composition information. These descriptors were used in cooperation with 12 popular machine learning (ML) algorithms to create 144 base-classifiers. To maximize the utility of these base-classifiers, we used a feature selection strategy to determine a collection of potential base-classifiers and integrated them to develop the meta-classifier. Comprehensive experiments based on both cross-validation and independent tests demonstrated the superior predictive performance of TROLLOPE compared with conventional ML classifiers, with cross-validation and independent test accuracies of 0.745 and 0.747, respectively. Finally, a user-friendly online web server of TROLLOPE (http://pmlabqsar.pythonanywhere.com/TROLLOPE) has been developed to serve research efforts in the large-scale identification of potential TCE-HCVs for follow-up experimental verification.

StackTTCA: a stacking ensemble learning-based framework for accurate and high-throughput identification of tumor T cell antigens.

BACKGROUND: The identification of tumor T cell antigens (TTCAs) is crucial for providing insights into their functional mechanisms and utilizing their potential in anticancer vaccines development. In this context, TTCAs are highly promising. Meanwhile, experimental technologies for discovering and characterizing new TTCAs are expensive and time-consuming. Although many machine learning (ML)-based models have been proposed for identifying new TTCAs, there is still a need to develop a robust model that can achieve higher rates of accuracy and precision. RESULTS: In this study, we propose a new stacking ensemble learning-based framework, termed StackTTCA, for accurate and large-scale identification of TTCAs. Firstly, we constructed 156 different baseline models by using 12 different feature encoding schemes and 13 popular ML algorithms. Secondly, these baseline models were trained and employed to create a new probabilistic feature vector. Finally, the optimal probabilistic feature vector was determined based the feature selection strategy and then used for the construction of our stacked model. Comparative benchmarking experiments indicated that StackTTCA clearly outperformed several ML classifiers and the existing methods in terms of the independent test, with an accuracy of 0.932 and Matthew's correlation coefficient of 0.866. CONCLUSIONS: In summary, the proposed stacking ensemble learning-based framework of StackTTCA could help to precisely and rapidly identify true TTCAs for follow-up experimental verification. In addition, we developed an online web server ( http://2pmlab.camt.cmu.ac.th/StackTTCA ) to maximize user convenience for high-throughput screening of novel TTCAs.

DeepAR: a novel deep learning-based hybrid framework for the interpretable prediction of androgen receptor antagonists.

Drug resistance represents a major obstacle to therapeutic innovations and is a prevalent feature in prostate cancer (PCa). Androgen receptors (ARs) are the hallmark therapeutic target for prostate cancer modulation and AR antagonists have achieved great success. However, rapid emergence of resistance contributing to PCa progression is the ultimate burden of their long-term usage. Hence, the discovery and development of AR antagonists with capability to combat the resistance, remains an avenue for further exploration. Therefore, this study proposes a novel deep learning (DL)-based hybrid framework, named DeepAR, to accurately and rapidly identify AR antagonists by using only the SMILES notation. Specifically, DeepAR is capable of extracting and learning the key information embedded in AR antagonists. Firstly, we established a benchmark dataset by collecting active and inactive compounds against AR from the ChEMBL database. Based on this dataset, we developed and optimized a collection of baseline models by using a comprehensive set of well-known molecular descriptors and machine learning algorithms. Then, these baseline models were utilized for creating probabilistic features. Finally, these probabilistic features were combined and used for the construction of a meta-model based on a one-dimensional convolutional neural network. Experimental results indicated that DeepAR is a more accurate and stable approach for identifying AR antagonists in terms of the independent test dataset, by achieving an accuracy of 0.911 and MCC of 0.823. In addition, our proposed framework is able to provide feature importance information by leveraging a popular computational approach, named SHapley Additive exPlanations (SHAP). In the meanwhile, the characterization and analysis of potential AR antagonist candidates were achieved through the SHAP waterfall plot and molecular docking. The analysis inferred that N-heterocyclic moieties, halogenated substituents, and a cyano functional group were significant determinants of potential AR antagonists. Lastly, we implemented an online web server by using DeepAR (at http://pmlabstack.pythonanywhere.com/DeepAR ). We anticipate that DeepAR could be a useful computational tool for community-wide facilitation of AR candidates from a large number of uncharacterized compounds.

Pretoria: An effective computational approach for accurate and high-throughput identification of CD8+ t-cell epitopes of eukaryotic pathogens.

T-cells recognize antigenic epitopes present on major histocompatibility complex (MHC) molecules, triggering an adaptive immune response in the host. T-cell epitope (TCE) identification is challenging because of the extensive number of undetermined proteins found in eukaryotic pathogens, as well as MHC polymorphisms. In addition, conventional experimental approaches for TCE identification are time-consuming and expensive. Thus, computational approaches that can accurately and rapidly identify CD8+ T-cell epitopes (TCEs) of eukaryotic pathogens based solely on sequence information may facilitate the discovery of novel CD8+ TCEs in a cost-effective manner. Here, Pretoria (Predictor of CD8+ TCEs of eukaryotic pathogens) is proposed as the first stack-based approach for accurate and large-scale identification of CD8+ TCEs of eukaryotic pathogens. In particular, Pretoria enabled the extraction and exploration of crucial information embedded in CD8+ TCEs by employing a comprehensive set of 12 well-known feature descriptors extracted from multiple groups, including physicochemical properties, composition-transition-distribution, pseudo-amino acid composition, and amino acid composition. These feature descriptors were then utilized to construct a pool of 144 different machine learning (ML)-based classifiers based on 12 popular ML algorithms. Finally, the feature selection method was used to effectively determine the important ML classifiers for the construction of our stacked model. The experimental results indicated that Pretoria is an accurate and effective computational approach for CD8+ TCE prediction; it was superior to several conventional ML classifiers and the existing method in terms of the independent test, with an accuracy of 0.866, MCC of 0.732, and AUC of 0.921. Additionally, to maximize user convenience for high-throughput identification of CD8+ TCEs of eukaryotic pathogens, a user-friendly web server of Pretoria (http://pmlabstack.pythonanywhere.com/Pretoria) was developed and made freely available.

PSRQSP: An effective approach for the interpretable prediction of quorum sensing peptide using propensity score representation learning.

Quorum sensing peptides (QSPs) are microbial signaling molecules involved in several cellular processes, such as cellular communication, virulence expression, bioluminescence, and swarming, in various bacterial species. Understanding QSPs is essential for identifying novel drug targets for controlling bacterial populations and pathogenicity. In this study, we present a novel computational approach (PSRQSP) for improving the prediction and analysis of QSPs. In PSRQSP, we develop a novel propensity score representation learning (PSR) scheme. Specifically, we utilized the PSR approach to extract and learn a comprehensive set of estimated propensities of 20 amino acids, 400 dipeptides, and 400 g-gap dipeptides from a pool of scoring card method-based models. Finally, to maximize the utility of the propensity scores, we explored a set of optimal propensity scores and combined them to construct a final meta-predictor. Our experimental results showed that combining multiview propensity scores was more beneficial for identifying QSPs than the conventional feature descriptors. Moreover, extensive benchmarking experiments based on the independent test were sufficient to demonstrate the predictive capability and effectiveness of PSRQSP by outperforming the conventional ML-based and existing methods, with an accuracy of 94.44% and AUC of 0.967. PSR-derived propensity scores were employed to determine the crucial physicochemical properties for a better understanding of the functional mechanisms of QSPs. Finally, we constructed an easy-to-use web server for the PSRQSP (http://pmlabstack.pythonanywhere.com/PSRQSP). PSRQSP is anticipated to be an efficient computational tool for accelerating the data-driven discovery of potential QSPs for drug discovery and development.

GPApred: The first computational predictor for identifying proteins with LPXTG-like motif using sequence-based optimal features.

The cell surface proteins of gram-positive bacteria are involved in many important biological functions, including the infection of host cells. Owing to their virulent nature, these proteins are also considered strong candidates for potential drug or vaccine targets. Among the various cell surface proteins of gram-positive bacteria, LPXTG-like proteins form a major class. These proteins have a highly conserved C-terminal cell wall sorting signal, which consists of an LPXTG sequence motif, a hydrophobic domain, and a positively charged tail. These surface proteins are targeted to the cell envelope by a sortase enzyme via transpeptidation. A variety of LPXTG-like proteins have been experimentally characterized; however, their number in public databases has increased owing to extensive bacterial genome sequencing without proper annotation. In the absence of experimental characterization, identifying and annotating these sequences is extremely challenging. Therefore, in this study, we developed the first machine learning-based predictor called GPApred, which can identify LPXTG-like proteins from their primary sequences. Using a newly constructed benchmark dataset, we explored different classifiers and five feature encodings and their hybrids. Optimal features were derived using the recursive feature elimination method, and these features were then trained using a support vector machine algorithm. The performance of different models was evaluated using independent datasets, and a final model (GPApred) was selected based on consistency during cross-validation and independent assessment. GPApred can be an effective tool for predicting LPXTG-like sequences and can be further employed for functional characterization or drug targeting. Availability: https://procarb.org/gpapred/.

PSRTTCA: A new approach for improving the prediction and characterization of tumor T cell antigens using propensity score representation learning.

Despite the arsenal of existing cancer therapies, the ongoing recurrence and new cases of cancer pose a serious health concern that necessitates the development of new and effective treatments. Cancer immunotherapy, which uses the body's immune system to combat cancer, is a promising treatment option. As a result, in silico methods for identifying and characterizing tumor T cell antigens (TTCAs) would be useful for better understanding their functional mechanisms. Although few computational methods for TTCA identification have been developed, their lack of model interpretability is a major drawback. Thus, developing computational methods for the effective identification and characterization of TTCAs is a critical endeavor. PSRTTCA, a new machine learning (ML)-based approach for improving the identification and characterization of TTCAs based on their primary sequences, is proposed in this study. Specifically, we introduce a new propensity score representation learning algorithm that allows one to generate various sets of propensity scores of amino acids, dipeptides, and g-gap dipeptides to be TTCAs. To enhance the predictive performance, optimal sets of variant propensity scores were determined and fed into the final meta-predictor (PSRTTCA). Benchmarking results revealed that PSRTTCA was a more precise and promising tool for the identification and characterization of TTCAs than conventional ML classifiers and existing methods. Furthermore, PSR-derived propensities of amino acids in becoming TTCAs are used to reveal the relationship between TTCAs and their informative physicochemical properties in order to provide insights into TTCA characteristics. Finally, a user-friendly online computational platform of PSRTTCA is publicly available at http://pmlabstack.pythonanywhere.com/PSRTTCA. The PSRTTCA predictor is anticipated to facilitate community-wide efforts in accelerating the discovery of novel TTCAs for cancer immunotherapy and other clinical applications.

The role of ncRNA regulatory mechanisms in diseases-case on gestational diabetes.

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease.

Feature fusion based VGGFusionNet model to detect COVID-19 patients utilizing computed tomography scan images.

COVID-19 is one of the most life-threatening and dangerous diseases caused by the novel Coronavirus, which has already afflicted a larger human community worldwide. This pandemic disease recovery is possible if detected in the early stage. We proposed an automated deep learning approach from Computed Tomography (CT) scan images to detect COVID-19 positive patients by following a four-phase paradigm for COVID-19 detection: preprocess the CT scan images; remove noise from test image by using anisotropic diffusion techniques; make a different segment for the preprocessed images; and train and test COVID-19 detection using Convolutional Neural Network (CNN) models. This study employed well-known pre-trained models, including AlexNet, ResNet50, VGG16 and VGG19 to evaluate experiments. 80% of images are used to train the network in the detection process, while the remaining 20% are used to test it. The result of the experiment evaluation confirmed that the VGG19 pre-trained CNN model achieved better accuracy (98.06%). We used 4861 real-life COVID-19 CT images for experiment purposes, including 3068 positive and 1793 negative images. These images were acquired from a hospital in Sao Paulo, Brazil and two other different data sources. Our proposed method revealed very high accuracy and, therefore, can be used as an assistant to help professionals detect COVID-19 patients accurately.

iAMAP-SCM: A Novel Computational Tool for Large-Scale Identification of Antimalarial Peptides Using Estimated Propensity Scores of Dipeptides.

Antimalarial peptides (AMAPs) varying in length, amino acid composition, charge, conformational structure, hydrophobicity, and amphipathicity reflect their diversity in antimalarial mechanisms. Due to the worldwide major health problem concerning antimicrobial resistance, these peptides possess great therapeutic value owing to their low incidences of drug resistance as compared to conventional antibiotics. Although well-known experimental methods are able to precisely determine the antimalarial activity of peptides, these methods are still time-consuming and costly. Thus, machine learning (ML)-based methods that are capable of identifying AMAPs rapidly by using only sequence information would be beneficial for the high-throughput identification of AMAPs. In this study, we propose the first computational model (termed iAMAP-SCM) for the large-scale identification and characterization of peptides with antimalarial activity by using only sequence information. Specifically, we employed an interpretable scoring card method (SCM) to develop iAMAP-SCM and estimate propensities of 20 amino acids and 400 dipeptides to be AMAPs in a supervised manner. Experimental results showed that iAMAP-SCM could achieve a maximum accuracy and Matthew's coefficient correlation of 0.957 and 0.834, respectively, on the independent test dataset. In addition, SCM-derived propensities of 20 amino acids and selected physicochemical properties were used to provide an understanding of the functional mechanisms of AMAPs. Finally, a user-friendly online computational platform of iAMAP-SCM is publicly available at http://pmlabstack.pythonanywhere.com/iAMAP-SCM. The iAMAP-SCM predictor is anticipated to assist experimental scientists in the high-throughput identification of potential AMAP candidates for the treatment of malaria and other clinical applications.

DeepThal: A Deep Learning-Based Framework for the Large-Scale Prediction of the α+-Thalassemia Trait Using Red Blood Cell Parameters.

Objectives: To develop a machine learning (ML)-based framework using red blood cell (RBC) parameters for the prediction of the α+-thalassemia trait (α+-thal trait) and to compare the diagnostic performance with a conventional method using a single RBC parameter or a combination of RBC parameters. Methods: A retrospective study was conducted on possible couples at risk for fetus with hemoglobin H (Hb H disease). Subjects with molecularly confirmed normal status (not thalassemia), α+-thal trait, and two-allele α-thalassemia mutation were included. Clinical parameters (age and gender) and RBC parameters (Hb, Hct, MCV, MCH, MCHC, RDW, and RBC count) obtained from their antenatal thalassemia screen were retrieved and analyzed using a machine learning (ML)-based framework and a conventional method. The performance of α+-thal trait prediction was evaluated. Results: In total, 594 cases (female/male: 330/264, mean age: 29.7 ± 6.6 years) were included in the analysis. There were 229 normal controls, 160 cases with the α+-thalassemia trait, and 205 cases in the two-allele α-thalassemia mutation category, respectively. The ML-derived model improved the diagnostic performance, giving a sensitivity of 80% and specificity of 81%. The experimental results indicated that DeepThal achieved a better performance compared with other ML-based methods in terms of the independent test dataset, with an accuracy of 80.77%, sensitivity of 70.59%, and the Matthews correlation coefficient (MCC) of 0.608. Of all the red blood cell parameters, MCH < 28.95 pg as a single parameter had the highest performance in predicting the α+-thal trait with the AUC of 0.857 and 95% CI of 0.816−0.899. The combination model derived from the binary logistic regression analysis exhibited improved performance with the AUC of 0.868 and 95% CI of 0.830−0.906, giving a sensitivity of 80.1% and specificity of 75.1%. Conclusions: The performance of DeepThal in terms of the independent test dataset is sufficient to demonstrate that DeepThal is capable of accurately predicting the α+-thal trait. It is anticipated that DeepThal will be a useful tool for the scientific community in the large-scale prediction of the α+-thal trait.

Improved prediction and characterization of blood-brain barrier penetrating peptides using estimated propensity scores of dipeptides.

The blood-brain barrier (BBB) is the primary barrier with a highly selective semipermeable border between blood vascular endothelial cells and the central nervous system. Since BBB can prevent drugs circulating in the blood from crossing into the interstitial fluid of the brain where neurons reside, many researchers are working hard on developing drug delivery systems to penetrate the BBB which currently poses a challenge. Thus, blood-brain barrier penetrating peptides (B3PPs) are an alternative neurotherapeutic for brain-related disorder since they can facilitate drug delivery into the brain. In the meanwhile, developing computational methods that are effective for both the identification and characterization of B3PPs in a cost-effective manner plays an important role for basic reach and in the pharmaceutical industry. Even though few computational methods for B3PP identification have been developed, their performance might fail in terms of generalization ability and interpretability. In this study, a novel and efficient scoring card method-based predictor (termed SCMB3PP) is presented for improving B3PP identification and characterization. To overcome the limitation of black-box computational approaches, the SCMB3PP predictor can automatically estimate amino acid and dipeptide propensities to be B3PPs. Both cross-validation and independent tests indicate that SCMB3PP can achieve impressive performance and outperform various popular machine learning-based methods and the existing methods on multiple independent test datasets. Furthermore, SCMB3PP-derived amino acid propensities were utilized to identify informative biophysical and biochemical properties for characterizing B3PPs. Finally, an online user-friendly web server ( http://pmlabstack.pythonanywhere.com/SCMB3PP ) is established to identify novel and potential B3PP cost-effectively. This novel computational approach is anticipated to facilitate the large-scale identification of high potential B3PP candidates for follow-up experimental validation.