Abstract
IL-17 cytokines are pro-inflammatory cytokines and are crucial in host defense against various microbes. Induction of these cytokines by microbial antigens has been investigated in the case of ischemic brain injury, gingivitis, candidiasis, autoimmune myocarditis, etc. In this study, we have investigated the ability of amino acid sequence of antigens to induce IL-17 response using machine-learning approaches. A total of 338 IL-17-inducing and 984 IL-17 non-inducing peptides were retrieved from Immune Epitope Database. 80% of the data were randomly selected as training dataset and rest 20% as validation dataset. To predict the IL-17-inducing ability of peptides/protein antigens, different sequence-based machine-learning models were developed. The performance of support vector machine (SVM) and random forest (RF) was compared with different parameters to predict IL-17-inducing epitopes (IIEs). The dipeptide composition-based SVM-model displayed an accuracy of 82.4% with Matthews correlation coefficient = 0.62 at polynomial (t = 1) kernel on 10-fold cross-validation and outperformed RF. Amino acid residues Leu, Ser, Arg, Asn, and Phe and dipeptides LL, SL, LK, IL, LI, NL, LR, FK, SF, and LE are abundant in IIEs. The present tool helps in the identification of IIEs using machine-learning approaches. The induction of IL-17 plays an important role in several inflammatory diseases, and identification of such epitopes would be of great help to the immunologists. It is freely available at http://metagenomics.iiserb.ac.in/IL17eScan/ and http://metabiosys.iiserb.ac.in/IL17eScan/.
Highlights
Human body harbors complex microbial communities which may exist in planktonic forms or as higher order structures termed as biofilms [1]
Ala, Asp, Gly, and Pro were found to be rich in IL-17 non-inducing epitope (INIE) (Figure 2; Data Sheet S1 in Supplementary Material)
We have developed an in silico method to predict the IL-17-inducing ability of peptides/proteins based on the sequence-based features derived from a set of experimentally validated IL-17-inducing epitope (IIE), and non-inducing epitopes obtained from the Immune Epitope Database (IEDB)
Summary
Human body harbors complex microbial communities which may exist in planktonic forms or as higher order structures termed as biofilms [1]. The interaction of the peripheral immune system with these microbes has an essential role in the pathophysiology of different diseases [2]. One of the key components of the peripheral immune system is IL-17 family of cytokines, which play regulatory roles in host defense and during inflammatory diseases. They mediate pro-inflammatory responses via surface receptors on target cells and play several protective roles in host defense against pathogens at epithelial and mucosal barriers including skin, colon, and lung [3]
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