GuiTope: an application for mapping random-sequence peptides to protein sequences

Rebecca F Halperin,Krupa Arun Navalkar,Phillip Stafford,Jack S Emery,Stephen Albert Johnston

doi:10.1186/1471-2105-13-1

Rebecca F Halperin, Krupa Arun Navalkar + Show 3 more

Open Access

https://doi.org/10.1186/1471-2105-13-1

Copy DOI

Abstract

BackgroundRandom-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task.ResultsGuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance.ConclusionsGuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC) at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.

Highlights

Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules
Peptide library methods generally fall into two categories: molecular display approaches such as phage display, and immobilized arrays such as SPOT
Though current array technology does not allow sufficient coverage of sequence space to contain sequences closely resembling natural protein sequences by chance, we have shown that experiments of this type still have utility for predicting monoclonal epitopes [8]

Summary

Results

GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance

Conclusions

Background

Methods

Results and discussion