Identification of cancer-specific motifs in mimotope profiles of serum antibody repertoire

BMC Bioinformatics

Research

Yurij Ionov¹  Ion Măndoiu²  Ekaterina Gerasimov³  Alex Zelikovsky³ 

[1] Department of Cancer Genetics, Roswell Park Cancer Institute, 14263, Buffalo, NY, USA;Department of Computer Science and Engineering, University of Connecticut, 06269, Storrs, CT, USA;Department of Computer Science, Georgia State University, 25 Park Place, 30303, Atlanta, GA, USA;

关键词: Random peptide phage display library;    Early cancer detection;    Immune response;    Peptide motifs;    Mimotope profile;   

DOI  :  10.1186/s12859-017-1661-5

来源: Springer

【 摘 要 】

BackgroundFor fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient’s own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4–7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients’ and healthy donors’ global peptide profiles of antibody specificities.ResultsDue to the enormously large number of peptide sequences contained in global peptide profiles generated by next generation sequencing, the large number of cancer and control sera is required to identify cancer-specific peptides with high degree of statistical significance. To decrease the number of peptides in profiles generated by nextgen sequencing without losing cancer-specific sequences we used for generation of profiles the phage library enriched by panning on the pool of cancer sera. To further decrease the complexity of profiles we used computational methods for transforming a list of peptides constituting the mimotope profiles to the list motifs formed by similar peptide sequences.ConclusionWe have shown that the amino-acid order is meaningful in mimotope motifs since they contain significantly more peptides than motifs among peptides where amino-acids are randomly permuted. Also the single sample motifs significantly differ from motifs in peptides drawn from multiple samples. Finally, multiple cancer-specific motifs have been identified.

【 授权许可】

CC BY   
© The Author(s) 2017