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Inadequate Reference Datasets Biased toward Short Non-epitopes Confound B-cell Epitope Prediction


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dc.contributorKh Shamsur Rahman, ksr0003@auburn.eduen_US
dc.creatorRahman, Kh. Shamsur
dc.creatorChowdhury, Erfan U.
dc.creatorSachse, Konrad
dc.creatorKaltenboeck, Bernhard
dc.date.accessioned2020-04-08T18:09:26Z
dc.date.available2020-04-08T18:09:26Z
dc.date.created2016-07-08
dc.identifier10.1074/jbc.M116.729020en_US
dc.identifier.urihttps://www.jbc.org/content/291/28/14585.full?sid=358e2ffc-eaa5-45a7-91ec-cf6cd79e1961en_US
dc.identifier.urihttp://hdl.handle.net/11200/49788
dc.description.abstractX-ray crystallography has shown that an antibody paratope typically binds 15-22 amino acids (aa) of an epitope, of which 2-5 randomly distributed amino acids contribute most of the binding energy. In contrast, researchers typically choose for B-cell epitope mapping short peptide antigens in antibody binding assays. Furthermore, short 6-11-aa epitopes, and in particular non-epitopes, are over-represented in published B-cell epitope datasets that are commonly used for development of B-cell epitope prediction approaches from protein antigen sequences. We hypothesized that such suboptimal length peptides result in weak antibody binding and cause false-negative results. We tested the influence of peptide antigen length on antibody binding by analyzing data on more than 900 peptides used for B-cell epitope mapping of immunodominant proteins of Chlamydia spp. We demonstrate that short 7-12-aa peptides of B-cell epitopes bind antibodies poorly; thus, epitope mapping with short peptide antigens falsely classifies many B-cell epitopes as non-epitopes. We also show in published datasets of confirmed epitopes and non-epitopes a direct correlation between length of peptide antigens and antibody binding. Elimination of short, 11-aa epitope/non-epitope sequences improved datasets for evaluation of in silico B-cell epitope prediction. Achieving up to 86% accuracy, protein disorder tendency is the best indicator of B-cell epitope regions for chlamydial and published datasets. For B-cell epitope prediction, the most effective approach is plotting disorder of protein sequences with the IUPred-L scale, followed by antibody reactivity testing of 16-30-aa peptides from peak regions. This strategy overcomes the well known inaccuracy of in silico B-cell epitope prediction from primary protein sequences.en_US
dc.formatPDFen_US
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCen_US
dc.relation.ispartofJOURNAL OF BIOLOGICAL CHEMISTRYen_US
dc.subjectANTIBODYen_US
dc.subjectANTIGENen_US
dc.subjectBIOINFORMATICSen_US
dc.subjectEPITOPE MAPPINGen_US
dc.subjectimmunogenicityen_US
dc.subjectprotein motifen_US
dc.subjectprotein-protein interactionen_US
dc.subjectOUTER-MEMBRANE PROTEINen_US
dc.subjectINTRINSICALLY UNSTRUCTURED PROTEINSen_US
dc.subjectCHLAMYDIA-TRACHOMATIS SEROVARen_US
dc.subjectAMINO-ACID RESIDUESen_US
dc.subjectANTIGENIC DETERMINANTSen_US
dc.subjectSECONDARY-STRUCTUREen_US
dc.subjectSOLVENT ACCESSIBILITYen_US
dc.subjectDISORDERED REGIONSen_US
dc.titleInadequate Reference Datasets Biased toward Short Non-epitopes Confound B-cell Epitope Predictionen_US
dc.typeCollectionen_US
dc.type.genreJournal Article, Academic Journalen_US
dc.citation.volume291en_US
dc.citation.issue28en_US
dc.citation.spage14585en_US
dc.citation.epage14599en_US
dc.description.statusPublisheden_US
dc.description.peerreviewYesen_US
dc.creator.orcidhttp://orcid.org/0000-0001-7243-8501en_US

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