TY - JOUR
T1 - Epitope mapping using combinatorial phage-display libraries
T2 - A graph-based algorithm
AU - Mayrose, Itay
AU - Shlomi, Tomer
AU - Rubinstein, Nimrod D.
AU - Gershoni, Jonathan M.
AU - Ruppin, Eytan
AU - Sharan, Roded
AU - Pupko, Tal
N1 - Funding Information:
We thank Dr Golan Yona for his suggestions and insightful comments, and Adi Stern, Osnat Penn, and Eyal Privman for critically reading the manuscript. We also thank Dr Michael Humbert and Dr Violaine Moreau for their assistance with the comparative analysis. T.P. was supported by an Israeli Science Foundation grant number 1208/04, by a grant in Complexity Science from the Yeshaia Horvitz Association, and by a grant from the Israeli Ministry of Science. R.S. is supported by an Alon fellowship and by a research grant from the Ministry of Science and Technology, Israel. E.R. is supported by the Tauber Fund, the Center for Complexity Science, and the Israeli Science Foundation. J.M.G. is supported by an ISF grant. T.S. is supported by the Tauber Fund. N.D.R. is a fellow of the Edmond J. Safra Program in Bioinformatics at Tel-Aviv University. Funding to pay the Open Access publication charges for this article was provided by a research grant from the Ministry of Science and Technology, Israel to T.P.
PY - 2007/1
Y1 - 2007/1
N2 - A phage-display library of random peptides is a combinatorial experimental technique that can be harnessed for studying antibody-antigen interactions. In this technique, a phage peptide library is scanned against an antibody molecule to obtain a set of peptides that are bound by the antibody with high affinity. This set of peptides is regarded as mimicking the genuine epitope of the antibody's interacting antigen and can be used to define it. Here we present PepSurf, an algorithm for mapping a set of affinity-selected peptides onto the solved structure of the antigen. The problem of epitope mapping is converted into the task of aligning a set of query peptides to a graph representing the surface of the antigen. The best match of each peptide is found by aligning it against virtually all possible paths in the graph. Following a clustering step, which combines the most significant matches, a predicted epitope is inferred. We show that PepSurf accurately predicts the epitope in four cases for which the epitope is known from a solved antibody-antigen co-crystal complex. We further examine the capabilities of PepSurf for predicting other types of protein-protein interfaces. The performance of PepSurf is compared to other available epitope mapping programs.
AB - A phage-display library of random peptides is a combinatorial experimental technique that can be harnessed for studying antibody-antigen interactions. In this technique, a phage peptide library is scanned against an antibody molecule to obtain a set of peptides that are bound by the antibody with high affinity. This set of peptides is regarded as mimicking the genuine epitope of the antibody's interacting antigen and can be used to define it. Here we present PepSurf, an algorithm for mapping a set of affinity-selected peptides onto the solved structure of the antigen. The problem of epitope mapping is converted into the task of aligning a set of query peptides to a graph representing the surface of the antigen. The best match of each peptide is found by aligning it against virtually all possible paths in the graph. Following a clustering step, which combines the most significant matches, a predicted epitope is inferred. We show that PepSurf accurately predicts the epitope in four cases for which the epitope is known from a solved antibody-antigen co-crystal complex. We further examine the capabilities of PepSurf for predicting other types of protein-protein interfaces. The performance of PepSurf is compared to other available epitope mapping programs.
UR - http://www.scopus.com/inward/record.url?scp=33846672181&partnerID=8YFLogxK
U2 - 10.1093/nar/gkl975
DO - 10.1093/nar/gkl975
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AN - SCOPUS:33846672181
SN - 0305-1048
VL - 35
SP - 69
EP - 78
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 1
ER -