Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing

Robert J. Pantazes, Jack Reifert, Joel Bozekowski, Kelly N. Ibsen, Joseph A Murray, Patrick S. Daugherty

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Disease-specific antibodies can serve as highly effective biomarkers but have been identified for only a relatively small number of autoimmune diseases. A method was developed to identify disease-specific binding motifs through integration of bacterial display peptide library screening, next-generation sequencing (NGS) and computational analysis. Antibody specificity repertoires were determined by identifying bound peptide library members for each specimen using cell sorting and performing NGS. A computational algorithm, termed Identifying Motifs Using Next-generation sequencing Experiments (IMUNE), was developed and applied to discover disease-and healthy control-specific motifs. IMUNE performs comprehensive pattern searches, identifies patterns statistically enriched in the disease or control groups and clusters the patterns to generate motifs. Using celiac disease sera as a discovery set, IMUNE identified a consensus motif (QPEQPF[PS]E) with high diagnostic sensitivity and specificity in a validation sera set, in addition to novel motifs. Peptide display and sequencing (Display-Seq) coupled with IMUNE analysis may thus be useful to characterize antibody repertoires and identify disease-specific antibody epitopes and biomarkers.

Original languageEnglish (US)
Article number30312
JournalScientific Reports
Volume6
DOIs
StatePublished - Aug 2 2016

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this