Abstract

Simple SummaryInterleukin-10 is a cytokine that exhibits potent anti-inflammatory characteristics that play an essential role in limiting the host’s immune response to pathogens and regulating the growth or differentiation of various immune cells. Moreover, interleukin-10 prediction via conventional approaches is time-consuming and labor-intensive. Hence, researchers are inclined towards an alternative approach to predict interleukin-10-inducing peptides. Additionally, numerous in silico tools are available to predict T cell epitopes. These methods generally follow a direct or indirect approach where they directly predict cytotoxic T-lymphocyte epitopes rather than major histocompatibility complex binders or indirectly predict single components of the T cell recognition pathway. However, very few studies are available that address cytokine-specific predictions. Our research utilized a computer-aided approach to develop a model to predict IL-10-inducing peptides. This study outperformed the existing state-of-the-art method and achieved an accuracy of 87.5% and Matthew’s correlation coefficient (MCC) of 0.755 on the hybrid feature types and outperformed an existing state-of-the-art method based on dipeptide compositions that achieved an accuracy of 81.24% and an MCC value of 0.59. Therefore, our model is promising to assist in predicting immunosuppressive peptides that induce interleukin-10 cytokines.Interleukin (IL)-10 is a homodimer cytokine that plays a crucial role in suppressing inflammatory responses and regulating the growth or differentiation of various immune cells. However, the molecular mechanism of IL-10 regulation is only partially understood because its regulation is environment or cell type-specific. In this study, we developed a computational approach, ILeukin10Pred (interleukin-10 prediction), by employing amino acid sequence-based features to predict and identify potential immunosuppressive IL-10-inducing peptides. The dataset comprises 394 experimentally validated IL-10-inducing and 848 non-inducing peptides. Furthermore, we split the dataset into a training set (80%) and a test set (20%). To train and validate the model, we applied a stratified five-fold cross-validation method. The final model was later evaluated using the holdout set. An extra tree classifier (ETC)-based model achieved an accuracy of 87.5% and Matthew’s correlation coefficient (MCC) of 0.755 on the hybrid feature types. It outperformed an existing state-of-the-art method based on dipeptide compositions that achieved an accuracy of 81.24% and an MCC value of 0.59. Our experimental results showed that the combination of various features achieved better predictive performance..

Highlights

  • IL-10 is a pleomorphic cytokine that exhibits a broad spectrum of pleiotropic effects in immune regulation and inflammation, initially discovered as a product of Th2 cells that inhibit the production of Th1

  • Later it was shown to be produced by various types of cells, including monocytes, macrophages, Th2 cells, mast cells, natural killer (NK) cells, and CD4+, CD25+, and forkhead box p3 (Foxp3)+ Tregs

  • Potent anti-inflammatory characteristics of IL-10 play a central role in maintaining normal tissue homeostasis

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Summary

Introduction

The complex network system of biological processes that protect organisms against infection is known as the immune system This system comprises several crucial cell types, such as B cells, T cells, antigen-presenting cells (APCs), and the biochemical mediators that help communicate and relay signals. All these factors have essential roles in the immune system in defending the body against harmful substances. Immunosuppression-mediated anti-inflammatory cytokines can address the deregulated function of the immune system These cytokines are an array of immunoregulatory molecules that limit the proinflammatory cytokine response, including interleukin (IL)-1 receptor a (1Ra), IL-4, IL-10, IL-11, IL-13, IL-33, IL-35, and IL-37 and transforming growth factor (TGF)-β

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