Receive a weekly summary and discussion of the top papers of the week by leading researchers in the field.

bioRxiv Preprint

Tumor Necrosis Factor alpha (TNF-) is a pleiotropic pro-inflammatory cytokine that plays a crucial role in controlling signaling pathways within the immune cells. Recent studies reported that the higher expression levels of TNF- is associated with the progression of several diseases including cancers, cytokine release syndrome in COVID-19 and autoimmune disorders. Thus, it is the need of the hour to develop immunotherapies or subunit vaccines to manage TNF- progression in various disease conditions. In the pilot study, we have proposed a host-specific in-silico tool for the prediction, designing and scanning of TNF- inducing epitopes. The prediction models were trained and validated on the experimentally validated TNF- inducing/non-inducing for human and mouse hosts. Firstly, we developed alignment free (machine learning based models using composition of peptides) methods for predicting TNF- inducing peptides and achieved maximum AUROC of 0.79 and 0.74 for human and mouse hosts, respectively. Secondly, alignment based (using BLAST) method has been used for predicting TNF- inducing epitopes. Finally, a hybrid method (combination of alignment free and alignment-based method) has been developed for predicting epitopes. Our hybrid method achieved maximum AUROC of 0.83 and 0.77 on an independent dataset for human and mouse hosts, respectively. We have also identified the potential TNF- inducing peptides in different proteins of HIV-1, HIV-2, SARS-CoV-2 and human insulin. Best models developed in this study has been incorporated in a webserver TNFepitope (https://webs.iiitd.edu.in/raghava/tnfepitope/), standalone package and GitLab (https://gitlab.com/raghavalab/tnfepitope).

Dhall, A.; Patiyal, S.; Choudhury, S.; Jain, S.; Narang, K.; Raghava, G. P. S.

2022-08-03