Accurately predicting nitrosylated tyrosine sites using probabilistic sequence information.

Post-translational modification (PTM) is defined as the enzymatic changes of proteins after the translation process in protein biosynthesis. Nitrotyrosine, which is one of the most important modifications of proteins, is interceded by the active nitrogen molecule. It is known to be associated with different diseases including autoimmune diseases characterized by chronic inflammation and cell damage. Currently, nitrotyrosine sites are identified using experimental approaches which are laborious and costly. In this study, we propose a new machine learning method called PredNitro to accurately predict nitrotyrosine sites. To build PredNitro, we use sequence coupling information from the neighboring amino acids of tyrosine residues along with a support vector machine as our classification technique.Our results demonstrates that PredNitro achieves 98.0% accuracy with more than 0.96 MCC and 0.99 AUC in both 5-fold cross-validation and jackknife cross-validation tests which are significantly better than those reported in previous studies. PredNitro is publicly available as an online predictor at: http://103.99.176.239/PredNitro.

predML-Site: Predicting Multiple Lysine PTM Sites With Optimal Feature Representation and Data Imbalance Minimization.

Identifying of post-translational modifications (PTM) is crucial in the study of computational proteomics, cell biology, pathogenesis, and drug development due to its role in many bio-molecular mechanisms. Computational methods for predicting multiple PTM at the same lysine residues, often referred to as K-PTM, is still evolving. This paper presents a novel computational tool, abbreviated as predML-Site, for predicting KPTM, such as acetylation, crotonylation, methylation, succinylation from an uncategorized peptide sample involving single, multiple, or no modification. For informative feature representation, multiple sequence encoding schemes, such as the sequence-coupling, binary encoding, k-spaced amino acid pairs, amino acid factor have been used with ANOVA and incremental feature selection. As a core predictor, a cost-sensitive SVM classifier has been adopted which effectively mitigates the effect of class-label imbalance in the dataset. predML-Site predicts multi-label PTM sites with 84.18% accuracy using the top 91 features. It has also achieved 85.34% aiming and 86.58% coverage rate which are much better than the existing state-of-the-art predictors on the same rigorous validation test. This performance indicates that predML-Site can be used as a supportive tool for further K-PTM study. For the convenience of the experimental scientists, predML-Site has been deployed as a user-friendly web-server at http://103.99.176.239/predML-Site.

Computational identification of multiple lysine PTM sites by analyzing the instance hardness and feature importance.

Identification of post-translational modifications (PTM) is significant in the study of computational proteomics, cell biology, pathogenesis, and drug development due to its role in many bio-molecular mechanisms. Though there are several computational tools to identify individual PTMs, only three predictors have been established to predict multiple PTMs at the same lysine residue. Furthermore, detailed analysis and assessment on dataset balancing and the significance of different feature encoding techniques for a suitable multi-PTM prediction model are still lacking. This study introduces a computational method named 'iMul-kSite' for predicting acetylation, crotonylation, methylation, succinylation, and glutarylation, from an unrecognized peptide sample with one, multiple, or no modifications. After successfully eliminating the redundant data samples from the majority class by analyzing the hardness of the sequence-coupling information, feature representation has been optimized by adopting the combination of ANOVA F-Test and incremental feature selection approach. The proposed predictor predicts multi-label PTM sites with 92.83% accuracy using the top 100 features. It has also achieved a 93.36% aiming rate and 96.23% coverage rate, which are much better than the existing state-of-the-art predictors on the validation test. This performance indicates that 'iMul-kSite' can be used as a supportive tool for further K-PTM study. For the convenience of the experimental scientists, 'iMul-kSite' has been deployed as a user-friendly web-server at http://103.99.176.239/iMul-kSite .

predPhogly-Site: Predicting phosphoglycerylation sites by incorporating probabilistic sequence-coupling information into PseAAC and addressing data imbalance.

Post-translational modification (PTM) involves covalent modification after the biosynthesis process and plays an essential role in the study of cell biology. Lysine phosphoglycerylation, a newly discovered reversible type of PTM that affects glycolytic enzyme activities, and is responsible for a wide variety of diseases, such as heart failure, arthritis, and degeneration of the nervous system. Our goal is to computationally characterize potential phosphoglycerylation sites to understand the functionality and causality more accurately. In this study, a novel computational tool, referred to as predPhogly-Site, has been developed to predict phosphoglycerylation sites in the protein. It has effectively utilized the probabilistic sequence-coupling information among the nearby amino acid residues of phosphoglycerylation sites along with a variable cost adjustment for the skewed training dataset to enhance the prediction characteristics. It has achieved around 99% accuracy with more than 0.96 MCC and 0.97 AUC in both 10-fold cross-validation and independent test. Even, the standard deviation in 10-fold cross-validation is almost negligible. This performance indicates that predPhogly-Site remarkably outperformed the existing prediction tools and can be used as a promising predictor, preferably with its web interface at http://103.99.176.239/predPhogly-Site.

Developmental expression of Neuregulin-3 in the rat central nervous system.

Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia. There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized. To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels. Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates. In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed. Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited. Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages. At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration. At postnatal ages, Nrg3 was abundantly expressed throughout the cerebral cortex and hippocampus. Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited. In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons. In the rodent brain, Nrg3 is the most abundantly expressed of the Nrgs and its patterns of expression differ both temporally and spatially from that of Nrg1 and Nrg2. These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.