Reliable B cell epitope predictions: impacts of method development and improved benchmarking.

The interaction between antibodies and antigens is one of the most important immune system mechanisms for clearing infectious organisms from the host. Antibodies bind to antigens at sites referred to as B-cell epitopes. Identification of the exact location of B-cell epitopes is essential in several...

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Autores principales:	Jens Vindahl Kringelum, Claus Lundegaard, Ole Lund, Morten Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b0ef4d99e3e24e8484e94c138063765c
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spelling	oai:doaj.org-article:b0ef4d99e3e24e8484e94c138063765c2021-11-18T05:52:35ZReliable B cell epitope predictions: impacts of method development and improved benchmarking.1553-734X1553-735810.1371/journal.pcbi.1002829https://doaj.org/article/b0ef4d99e3e24e8484e94c138063765c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300419/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The interaction between antibodies and antigens is one of the most important immune system mechanisms for clearing infectious organisms from the host. Antibodies bind to antigens at sites referred to as B-cell epitopes. Identification of the exact location of B-cell epitopes is essential in several biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping of B-cell epitopes has been moderate. Several issues regarding the evaluation data sets may however have led to the performance values being underestimated: Rarely, all potential epitopes have been mapped on an antigen, and antibodies are generally raised against the antigen in a given biological context not against the antigen monomer. Improper dealing with these aspects leads to many artificial false positive predictions and hence to incorrect low performance values. To demonstrate the impact of proper benchmark definitions, we here present an updated version of the DiscoTope method incorporating a novel spatial neighborhood definition and half-sphere exposure as surface measure. Compared to other state-of-the-art prediction methods, Discotope-2.0 displayed improved performance both in cross-validation and in independent evaluations. Using DiscoTope-2.0, we assessed the impact on performance when using proper benchmark definitions. For 13 proteins in the training data set where sufficient biological information was available to make a proper benchmark redefinition, the average AUC performance was improved from 0.791 to 0.824. Similarly, the average AUC performance on an independent evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version of DiscoTope is available at www.cbs.dtu.dk/services/DiscoTope-2.0.Jens Vindahl KringelumClaus LundegaardOle LundMorten NielsenPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 12, p e1002829 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jens Vindahl Kringelum Claus Lundegaard Ole Lund Morten Nielsen Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
description	The interaction between antibodies and antigens is one of the most important immune system mechanisms for clearing infectious organisms from the host. Antibodies bind to antigens at sites referred to as B-cell epitopes. Identification of the exact location of B-cell epitopes is essential in several biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping of B-cell epitopes has been moderate. Several issues regarding the evaluation data sets may however have led to the performance values being underestimated: Rarely, all potential epitopes have been mapped on an antigen, and antibodies are generally raised against the antigen in a given biological context not against the antigen monomer. Improper dealing with these aspects leads to many artificial false positive predictions and hence to incorrect low performance values. To demonstrate the impact of proper benchmark definitions, we here present an updated version of the DiscoTope method incorporating a novel spatial neighborhood definition and half-sphere exposure as surface measure. Compared to other state-of-the-art prediction methods, Discotope-2.0 displayed improved performance both in cross-validation and in independent evaluations. Using DiscoTope-2.0, we assessed the impact on performance when using proper benchmark definitions. For 13 proteins in the training data set where sufficient biological information was available to make a proper benchmark redefinition, the average AUC performance was improved from 0.791 to 0.824. Similarly, the average AUC performance on an independent evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version of DiscoTope is available at www.cbs.dtu.dk/services/DiscoTope-2.0.
format	article
author	Jens Vindahl Kringelum Claus Lundegaard Ole Lund Morten Nielsen
author_facet	Jens Vindahl Kringelum Claus Lundegaard Ole Lund Morten Nielsen
author_sort	Jens Vindahl Kringelum
title	Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
title_short	Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
title_full	Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
title_fullStr	Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
title_full_unstemmed	Reliable B cell epitope predictions: impacts of method development and improved benchmarking.
title_sort	reliable b cell epitope predictions: impacts of method development and improved benchmarking.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b0ef4d99e3e24e8484e94c138063765c
work_keys_str_mv	AT jensvindahlkringelum reliablebcellepitopepredictionsimpactsofmethoddevelopmentandimprovedbenchmarking AT clauslundegaard reliablebcellepitopepredictionsimpactsofmethoddevelopmentandimprovedbenchmarking AT olelund reliablebcellepitopepredictionsimpactsofmethoddevelopmentandimprovedbenchmarking AT mortennielsen reliablebcellepitopepredictionsimpactsofmethoddevelopmentandimprovedbenchmarking
_version_	1718424749084770304

Reliable B cell epitope predictions: impacts of method development and improved benchmarking.

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