Identification of conformational B-cell Epitopes in an antigen from its primary sequence

Abstract

BackgroundOne of the major challenges in the field of vaccine design is to predict conformational B-cell epitopes in an antigen. In the past, several methods have been developed for predicting conformational B-cell epitopes in an antigen from its tertiary structure. This is the first attempt in this area to predict conformational B-cell epitope in an antigen from its amino acid sequence.ResultsAll Support vector machine (SVM) models were trained and tested on 187 non-redundant protein chains consisting of 2261 antibody interacting residues of B-cell epitopes. Models have been developed using binary profile of pattern (BPP) and physiochemical profile of patterns (PPP) and achieved a maximum MCC of 0.22 and 0.17 respectively. In this study, for the first time SVM model has been developed using composition profile of patterns (CPP) and achieved a maximum MCC of 0.73 with accuracy 86.59%. We compare our CPP based model with existing structure based methods and observed that our sequence based model is as good as structure based methods.ConclusionThis study demonstrates that prediction of conformational B-cell epitope in an antigen is possible from is primary sequence. This study will be very useful in predicting conformational B-cell epitopes in antigens whose tertiary structures are not available. A web server CBTOPE has been developed for predicting B-cell epitope http://www.imtech.res.in/raghava/cbtope/.

Persistence, Immune Response, and Antigenic Variation of Mycoplasma genitalium in an Experimentally Infected Pig-Tailed Macaque (Macaca nemestrina)

“…The variable region B amino acid sequences of the mycobacterial G37-C inoculum and the week 8 variant were analyzed for the presence of B-cell epitopes with the EMBOSS antigenic (http://emboss.bioinformatics.nl/cgi-bin/emboss/antigenic) and BepiPred 1.0 (http://www.cbs.dtu.dk/services/BepiPred/) ( [51]) programs using a wide range of epitope lengths and thresholds, respectively. The full-length MgpB protein of strain G37-C was analyzed for predicted conformational B-cell epitopes using the CBTOPE program (http://www .imtech.res.in/raghava/cbtope/ [52]) with a support vector machine threshold of Ϫ0.3. The sequence of the full-length week 8 variant MgpB is unknown and consequently was not searched for conformational epitopes.…”

Antibody and Antigen Contact Residues Define Epitope and Paratope Size and Structure

“…A number of researchers have reported identifying CR of Abs and Ags by analysis of publicly available crystal structures (10)(11)(12). A large body of work in this field is aimed at identifying CR as a means of developing algorithms for predicting B cell epitopes (10,(13)(14)(15)(16)(17), whereas others have focused on analyzing or predicting CR in CDR of Abs (8,(18)(19)(20). The majority of the existing studies define two residues to be in contact when they are within a specified distance of each other.…”

“…The majority of the existing studies define two residues to be in contact when they are within a specified distance of each other. Many researchers use 4 Å as the definition of CR (10,(14)(15)(16)(17), and the Molecular Modeling Database (21), at the National Center for Biotechnology Information, defines protein interactions using a 4-Å cutoff. One group has published several works using 6 Å (13,20,22) and reported that their conclusions were unaffected by cutoffs ranging from 4 to 6 Å (20).…”

Immunomics: a 21st century approach to vaccine development for complex pathogens

“…However, many B-cell epitopes are conformational and discontinuous (Braga-Neto and Marques, 2006; Ansari and Raghava, 2010), corresponding to the tridimensional features on the surface of the antigen where recognition by the immune system occurs (BragaNeto and Marques, 2006). This creates difficulties for the bioinformatic prediction of B-cell epitopes.…”