Identification of Antigenic Regions Responsible for inducing Type 1 diabetes mellitus

Abstract

There are a number of antigens that induce autoimmune response against {beta}-cells, leading to Type 1 diabetes mellitus (T1DM). Recently several antigen-specific immunotherapies have been developed to treat T1DM. Thus identification of T1DM associated peptides with antigenic regions or epitopes is important for peptide based-therapeutics (e.g., immunotherapeutic). In this study, for the first time an attempt has been made to develop a method for predicting, designing and scanning of T1DM associated peptides with high precision. We analyzed 815 T1DM associated peptides and observed that these peptides are not associated with a specific class of HLA alleles. Thus, HLA binder prediction methods are not suitable for predicting T1DM associated peptides. Firstly, we developed a similarity/alignment based method using BLAST and achieved a high probability of correct hits with poor coverage. Secondly, we developed an alignment free method using machine learning techniques and got maximum AUROC 0.89 using dipeptide composition. Finally, we developed a hybrid method that combines the strength of both alignment free and alignment based methods and achieve maximum AUROC 0.95 with MCC 0.81 on independent dataset. We developed a webserver "DMPPred" and standalone server, for predicting, designing and scanning of T1DM associated peptides (https://webs.iiitd.edu.in/raghava/dmppred/). Key PointsO_LIPrediction of peptides responsible for inducing immune system against {beta}-cells C_LIO_LICompilation and analysis of Type 1 diabetes associated HLA binders C_LIO_LIBLAST based similarity search against Type 1diabetes associated peptides C_LIO_LIAlignment free method using machine learning techniques and composition C_LIO_LIA hybrid method using alignment free and alignment based approach C_LI Authors BiographyO_LINishant Kumar is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India C_LIO_LISumeet Patiyal is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India C_LIO_LIShubham Choudhury is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India C_LIO_LIRitu Tomer is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India C_LIO_LIAnjali Dhall is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. C_LIO_LIGajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. C_LI