title: A computational method for designing diverse linear epitopes including citrullinated peptides with desired binding affinities to intravenous immunoglobulin.
abstract: BACKGROUND
  Understanding the interactions between antibodies and the linear epitopes that they recognize is an important task in the study of immunological diseases. We present a novel computational method for the design of linear epitopes of specified binding affinity to Intravenous Immunoglobulin (IVIg).
  
  
  RESULTS
  We show that the method, called Pythia-design can accurately design peptides with both high-binding affinity and low binding affinity to IVIg. To show this, we experimentally constructed and tested the computationally constructed designs. We further show experimentally that these designed peptides are more accurate that those produced by a recent method for the same task. Pythia-design is based on combining random walks with an ensemble of probabilistic support vector machines (SVM) classifiers, and we show that it produces a diverse set of designed peptides, an important property to develop robust sets of candidates for construction. We show that by combining Pythia-design and the method of (PloS ONE 6(8):23616, 2011), we are able to produce an even more accurate collection of designed peptides. Analysis of the experimental validation of Pythia-design peptides indicates that binding of IVIg is favored by epitopes that contain trypthophan and cysteine.
  
  
  CONCLUSIONS
  Our method, Pythia-design, is able to generate a diverse set of binding and non-binding peptides, and its designs have been experimentally shown to be accurate.
authors.affiliation: Department of Computer Science, Stony Brook, NY, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Patro
authors.affiliation: IBM T.J. Watson Research Center, Yorktown Heights, NY, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Norel
authors.affiliation: IBM T.J. Watson Research Center, Yorktown Heights, NY, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Prill
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, UK.
authors.forename: Julio
authors.initials: J
authors.lastname: Saez-Rodriguez
authors.affiliation: Institute of Immunology, University of Rostock, Rostock, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lorenz
authors.affiliation: Institute of Immunology, University of Rostock, Rostock, Germany.|Gesellschaft für Individualisierte Medizin (IndyMed) mbH, Rostock, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Steinbeck
authors.affiliation: Gesellschaft für Individualisierte Medizin (IndyMed) mbH, Rostock, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Ziems
authors.affiliation: Department of Intelligent Systems, Jožef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Mitja
authors.initials: M
authors.lastname: Luštrek
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Barbarini
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tiengo
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bellazzi
authors.affiliation: Institute of Immunology, University of Rostock, Rostock, Germany.|Gesellschaft für Individualisierte Medizin (IndyMed) mbH, Rostock, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Thiesen
authors.affiliation: IBM T.J. Watson Research Center, Yorktown Heights, NY, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
authors.affiliation: Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. carlk@cs.cmu.edu.
authors.forename: Carl
authors.initials: C
authors.lastname: Kingsford
mesh_terms: D002956:Citrulline / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D003545:Cysteine / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D015203:Reproducibility of Results; D060388:Support Vector Machine; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000939:Epitopes; D016756:Immunoglobulins, Intravenous; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; D014364:Tryptophan; D003545:Cysteine
keywords: Antibodies; Machine learning; Protein binding; Protein design