Title
Computational B-cell epitope identification and production of neutralizing murine antibodies against Atroxlysin-I
Date Issued
01 December 2018
Access level
open access
Resource Type
journal article
Author(s)
Kozlova E.E.G.
Cerf L.
Schneider F.S.
Viart B.T.
NGuyen C.
Steiner B.T.
de Almeida Lima S.
Molina F.
Duarte C.G.
Felicori L.
Machado-de-Ávila R.A.
Instituto de Ciências Biológicas
Publisher(s)
Nature Publishing Group
Abstract
Epitope identification is essential for developing effective antibodies that can detect and neutralize bioactive proteins. Computational prediction is a valuable and time-saving alternative for experimental identification. Current computational methods for epitope prediction are underused and undervalued due to their high false positive rate. In this work, we targeted common properties of linear B-cell epitopes identified in an individual protein class (metalloendopeptidases) and introduced an alternative method to reduce the false positive rate and increase accuracy, proposing to restrict predictive models to a single specific protein class. For this purpose, curated epitope sequences from metalloendopeptidases were transformed into frame-shifted Kmers (3 to 15 amino acid residues long). These Kmers were decomposed into a matrix of biochemical attributes and used to train a decision tree classifier. The resulting prediction model showed a lower false positive rate and greater area under the curve when compared to state-of-the-art methods. Our predictions were used for synthesizing peptides mimicking the predicted epitopes for immunization of mice. A predicted linear epitope that was previously undetected by an experimental immunoassay was able to induce neutralizing-antibody production in mice. Therefore, we present an improved prediction alternative and show that computationally identified epitopes can go undetected during experimental mapping.
Volume
8
Issue
1
Language
English
OCDE Knowledge area
Inmunología
Scopus EID
2-s2.0-85054582853
PubMed ID
Source
Scientific Reports
Sponsor(s)
The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil; Fundação de Amparo à Pesquisa do Estado de Santa Catarina, Brazil; and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil, for financial support; Centro Nacional de Supercomputação (CESUP) as well as Dr. José Maria Gutiérrez (Instituto Clodomiro Picado), Facultad de Microbiología, Universidad de Costa Rica, for providing the Bap1 protein.
Sources of information: Directorio de Producción Científica Scopus