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      BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes

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          Abstract

          Antibodies have become an indispensable tool for many biotechnological and clinical applications. They bind their molecular target (antigen) by recognizing a portion of its structure (epitope) in a highly specific manner. The ability to predict epitopes from antigen sequences alone is a complex task. Despite substantial effort, limited advancement has been achieved over the last decade in the accuracy of epitope prediction methods, especially for those that rely on the sequence of the antigen only. Here, we present BepiPred-2.0 ( http://www.cbs.dtu.dk/services/BepiPred/), a web server for predicting B-cell epitopes from antigen sequences. BepiPred-2.0 is based on a random forest algorithm trained on epitopes annotated from antibody-antigen protein structures. This new method was found to outperform other available tools for sequence-based epitope prediction both on epitope data derived from solved 3D structures, and on a large collection of linear epitopes downloaded from the IEDB database. The method displays results in a user-friendly and informative way, both for computer-savvy and non-expert users. We believe that BepiPred-2.0 will be a valuable tool for the bioinformatics and immunology community.

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          Most cited references16

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          Measuring the accuracy of diagnostic systems.

          J Swets (1988)
          Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
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            The immune epitope database (IEDB) 3.0

            The IEDB, www.iedb.org, contains information on immune epitopes—the molecular targets of adaptive immune responses—curated from the published literature and submitted by National Institutes of Health funded epitope discovery efforts. From 2004 to 2012 the IEDB curation of journal articles published since 1960 has caught up to the present day, with >95% of relevant published literature manually curated amounting to more than 15 000 journal articles and more than 704 000 experiments to date. The revised curation target since 2012 has been to make recent research findings quickly available in the IEDB and thereby ensure that it continues to be an up-to-date resource. Having gathered a comprehensive dataset in the IEDB, a complete redesign of the query and reporting interface has been performed in the IEDB 3.0 release to improve how end users can access this information in an intuitive and biologically accurate manner. We here present this most recent release of the IEDB and describe the user testing procedures as well as the use of external ontologies that have enabled it.
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              Improved method for predicting linear B-cell epitopes

              Background B-cell epitopes are the sites of molecules that are recognized by antibodies of the immune system. Knowledge of B-cell epitopes may be used in the design of vaccines and diagnostics tests. It is therefore of interest to develop improved methods for predicting B-cell epitopes. In this paper, we describe an improved method for predicting linear B-cell epitopes. Results In order to do this, three data sets of linear B-cell epitope annotated proteins were constructed. A data set was collected from the literature, another data set was extracted from the AntiJen database and a data sets of epitopes in the proteins of HIV was collected from the Los Alamos HIV database. An unbiased validation of the methods was made by testing on data sets on which they were neither trained nor optimized on. We have measured the performance in a non-parametric way by constructing ROC-curves. Conclusion The best single method for predicting linear B-cell epitopes is the hidden Markov model. Combining the hidden Markov model with one of the best propensity scale methods, we obtained the BepiPred method. When tested on the validation data set this method performs significantly better than any of the other methods tested. The server and data sets are publicly available at .
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                03 July 2017
                02 May 2017
                02 May 2017
                : 45
                : Web Server issue
                : W24-W29
                Affiliations
                [1 ]Department of Bio and Health Informatics, Technical University of Denmark, Kgs. Lyngby 2800, Denmark
                [2 ]La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
                [3 ]Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +45 4525 2489; Fax: +45 4593 1585; Email paolo.marcatili@ 123456gmail.com . Correspondence may also be addressed to Morten Nielsen. Email: mniel@ 123456cbs.dtu.dk
                Article
                gkx346
                10.1093/nar/gkx346
                5570230
                28472356
                3a560727-6f36-4b08-a051-a64cd039fc0c
                © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 20 April 2017
                : 04 April 2017
                : 02 February 2017
                Page count
                Pages: 6
                Categories
                Web Server Issue

                Genetics
                Genetics

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