Accurately Predicting Glutarylation Sites Using Sequential Bi-Peptide-Based Evolutionary Features

Abstract

Post Translational Modification (PTM) is defined as the alteration of protein sequence upon interaction with different macromolecules after the translation process. Glutarylation is considered one of the most important PTMs, which is associated with a wide range of cellular functioning, including metabolism, translation, and specified separate subcellular localizations. During the past few years, a wide range of computational approaches has been proposed to predict Glutarylation sites. However, despite all the efforts that have been made so far, the prediction performance of the Glutarylation sites has remained limited. One of the main challenges to tackle this problem is to extract features with significant discriminatory information. To address this issue, we propose a new machine learning method called BiPepGlut using the concept of a bi-peptide-based evolutionary method for feature extraction. To build this model, we also use the Extra-Trees (ET) classifier for the classification purpose, which, to the best of our knowledge, has never been used for this task. Our results demonstrate BiPepGlut is able to significantly outperform previously proposed models to tackle this problem. BiPepGlut achieves 92.0%, 84.8%, 95.6%, 0.82, and 0.88 in accuracy, sensitivity, specificity, Matthew’s Correlation Coefficient, and F1-score, respectively. BiPepGlut is implemented as a publicly available online predictor.

Unique Posttranslational Modification Sites of Acetylation, Citrullination, Glutarylation, and Phosphorylation Are Found to Be Specific to the Proteins Partitioned in the Triton X-114 Fractions of Leptospira

“…Glutarylation is a crucial PTM, associated with a range of cellular metabolism, translation, and subcellular localizations. 32 The pellet fraction contained phosphorylation as the highest modification found in serine, threonine, and tyrosine residues. Phosphorylations of serine, threonine, and tyrosine are well-known bacterial transcriptional regulators that regulate gene expression and signal transduction signaling networks.…”

“…Acetylation plays a significant role in primary and secondary metabolism, virulence, transcription, and translation. , Acetylated lysyl residues of bacterial proteins can change the cellular physiology that can play roles in transcription, translation, cellular metabolism, and virulence. , The detergent fraction was mainly associated with glutarylation. Glutarylation is a crucial PTM, associated with a range of cellular metabolism, translation, and subcellular localizations . The pellet fraction contained phosphorylation as the highest modification found in serine, threonine, and tyrosine residues.…”

MP-VHPPI: Meta predictor for viral host protein-protein interaction prediction in multiple hosts and viruses

“…Therefore, the ET classifier provides independent trees which yield better accuracy scores and low variance across different classes. Considering the increasing usage of ET classifiers in proteomics sequence analysis tasks including glutarylation sites prediction ( 73 ), non-coding RNA-protein interaction prediction ( 74 ), and protein stability changes estimation ( 75 ). Overall, the ET classifier marks an average performance of more than 80% on these tasks.…”

Functions and Mechanisms of Lysine Glutarylation in Eukaryotes

“…A new type of glutaric acid site predictor PUL-GLU was developed by using positive unlabeled (PU) learning technology. Based on the evolutionary characteristics of double peptides, Arafat et al (2020) used Extra-Trees (ET) classifier to build the model BiPepGlut. Recently, Dou et al (2021) believed that the physical and chemical properties of charge, polarity, and van der Waals volume play a key role in the recognition of protein glutarylation, especially the positively charged R and K residues around the Kglu sites.…”