Blood-brain barrier peptides (BBBP) could significantly improve the delivery of drugs to the brain, paving the way for new treatments for central nervous system (CNS) disorders. The primary challenge in treating CNS disorders lies in the difficulty pharmaceutical agent's face in crossing the BBB. Almost 98% of small molecule drugs and nearly all large molecule drugs fail to penetrate the BBB effectively. Thus, identifying these peptides is vital for advancements in healthcare. This study introduces an enhanced intelligent computational model called BBB-PEP- Evolutionary Scale Modeling (ESM), designed to identify BBBP. The relative positions, reverse position and statistical moment-based features have been utilized on the existing benchmark dataset. For classification purpose, six deep classifiers such as fully connected networks, convolutional neural network, simple recurrent neural networks, long short-term memory (LSTM), bidirectional LSTM, and gated recurrent unit have been utilized. In addition to harnessing the effectiveness of the pre-trained model, a protein language model ESM 2.0 has been fine-tuned on a benchmark dataset for BBBP classification. Three tests such as self-consistency, independent set testing, and five-fold cross-validation have been utilized for evaluation purposes with evaluation metrics includes accuracy, specificity, sensitivity, and Matthews correlation coefficient. The fine-tuned model ESM 2.0 has shown superior results as compared to employed classifiers and surpasses the existing benchmark studies. This system will support future research and the scientific community in the computational identification of BBBP.

B-cell epitopes have the capability to recognize and attach to the surface of antigen receptors to stimulate the immune system against pathogens. Identification of B-cell epitopes from antigens has a great significance in several biomedical and biotechnological applications, provides support in the development of therapeutics, design and development of an epitope-based vaccine and antibody production. However, the identification of epitopes with experimental mapping approaches is a challenging job and usually requires extensive laboratory efforts. However, considerable efforts have been placed for the identification of epitopes using computational methods in the recent past but deprived of considerable achievements. In this study, we present LBCEPred, a python-based web-tool (http://lbcepred.pythonanywhere.com/), build with random forest classifier and statistical moment-based descriptors to predict the B-cell epitopes from the protein sequences. LBECPred outperforms all sequence-based available models that are currently in use for the B-cell epitopes prediction, with 0.868 accuracy value and 0.934 area under the curve. Moreover, the prediction performance of proposed models compared to other state-of-the-art models is 56.3% higher on average for Mathews Correlation Coefficient. LBCEPred is easy to use tool even for novice users and has also shown the models stability and reliability, thus we believe in its significant contribution to the research community and the area of bioinformatics.

Replication of DNA is an important process for the cell division cycle, gene expression regulation and other biological evolution processes. It also has a crucial role in a living organism's physical growth and structure. Replication of DNA comprises of three stages known as initiation, elongation and termination, whereas the origin of replication sites (ORI) is the location of initiation of the DNA replication process. There exist various methodologies to identify ORIs in the genomic sequences, however, these methods have used either extensive computations for execution, or have limited optimization for the large datasets. Herein, a model called ORI-Deep is proposed to identify ORIs from the multiple cell type genomic sequence benchmark data. An efficient method is proposed using a deep neural network to identify ORIs for four different eukaryotic species. For better representation of data, a feature vector is constructed using statistical moments for the training and testing of data and is further fed to a long short-term memory (LSTM) network. To prove the effectiveness of the proposed model, we applied several validation techniques at different levels to obtain seven accuracy metrics, and the accuracy score for self-consistency, 10-fold cross-validation, jackknife and the independent set test is observed to be 0.977, 0.948, 0.976 and 0.977, respectively. Based on the results, it can be concluded that ORI-Deep can efficiently predict the sites of origin replication in DNA sequence with high accuracy. Webserver for ORI-Deep is available at (https://share.streamlit.io/waqarhusain/orideep/main/app.py), whereas source code is available at (https://github.com/WaqarHusain/OriDeep).

Among all the PTMs, the protein phosphorylation is pivotal for various pathological and physiological processes. About 30 percent of eukaryotic proteins undergo the phosphorylation modification, leading to various changes in conformation, function, stability, localization, and so forth. In eukaryotic proteins, phosphorylation occurs on serine (S), Threonine (T) and Tyrosine (Y) residues. Among these all, serine phosphorylation has its own importance as it is associated with various importance biological processes, including energy metabolism, signal transduction pathways, cell cycling, and apoptosis. Thus, its identification is important, however, the in vitro, ex vivo and in vivo identification can be laborious, time-taking and costly. There is a dire need of an efficient and accurate computational model to help researchers and biologists identifying these sites, in an easy manner. Herein, we propose a novel predictor for identification of Phosphoserine sites (PhosS) in proteins, by integrating the Chou's Pseudo Amino Acid Composition (PseAAC) with deep features. We used well-known DNNs for both the tasks of learning a feature representation of peptide sequences and performing classifications. Among different DNNs, the best score is shown by Covolutional Neural Network based model which renders CNN based prediction model the best for Phosphoserine prediction. Based on these results, it is concluded that the proposed model can help to identify PhosS sites in a very efficient and accurate manner which can help scientists understand the mechanism of this modification in proteins.

Glycosylation of proteins in eukaryote cells is an important and complicated post-translation modification due to its pivotal role and association with crucial physiological functions within most of the proteins. Identification of glycosylation sites in a polypeptide chain is not an easy task due to multiple impediments. Analytical identification of these sites is expensive and laborious. There is a dire need to develop a reliable computational method for precise determination of such sites which can help researchers to save time and effort. Herein, we propose a novel predictor namely iGlycoS-PseAAC by integrating the Chou's Pseudo Amino Acid Composition (PseAAC) and relative/absolute position-based features. The self-consistency results show that the accuracy revealed by the model using the benchmark dataset for prediction of O-linked glycosylation having serine sites is 98.8 percent. The overall accuracy of predictor achieved through 10-fold cross validation by combining the positive and negative results is 97.2 percent. The overall accuracy achieved through Jackknife test is 96.195 percent by aggregating of all the prediction results. Thus the proposed predictor can help in predicting the O-linked glycosylated serine sites in an efficient and accurate way. The overall results show that the accuracy of the iGlycoS-PseAAC is higher than the existing tools.

Protein phosphorylation is one of the key mechanism in prokaryotes and eukaryotes and is responsible for various biological functions such as protein degradation, intracellular localization, the multitude of cellular processes, molecular association, cytoskeletal dynamics, and enzymatic inhibition/activation. Phosphohistidine (PhosH) has a key role in a number of biological processes, including central metabolism to signalling in eukaryotes and bacteria. Thus, identification of phosphohistidine sites in a protein sequence is crucial, and experimental identification can be expensive, time-taking, and laborious. To address this problem, here, we propose a novel computational model namely iPhosH-PseAAC for prediction of phosphohistidine sites in a given protein sequence using pseudo amino acid composition (PseAAC), statistical moments, and position relative features. The results of the proposed predictor are validated through self-consistency testing, 10-fold cross-validation, and jackknife testing. The self-consistency validation gave the 100 percent accuracy, whereas, for cross-validation, the accuracy achieved is 94.26 percent. Moreover, jackknife testing gave 97.07 percent accuracy for the proposed model. Thus, the proposed model iPhosH-PseAAC for prediction of iPhosH site has the great ability to predict the PhosH sites in given proteins.