K-TOPE

K-TOPE identifies antibody-binding epitopes within proteins and proteomes by analyzing next-generation sequencing data from antibody-selected peptide libraries to characterize antibody specificity.

Key Features:

• Generalizable strategy: Analyzes next-generation sequencing data from randomly selected antibody-binding peptides across 273 distinct sera and is applicable to both monoclonal and polyclonal antibodies.
• K-mer tiling technique: Tiles candidate antigen sequences into short overlapping k-mers and measures k-mer enrichment in the antibody-binding peptide dataset relative to background to pinpoint potential epitopes.
• Validation and accuracy: Recovers known epitopes targeted by antibodies with characterized specificity as a positive control.
• Broad proteome application: Applied to 2,908 proteins from 400 viral taxa infecting humans to identify epitopes recognized across specimens, including enteroviruses, Epstein-Barr virus, Staphylococcus, and Streptococcus.
• Consistency with mapped epitopes: Identified common viral and bacterial epitopes that agree with previously mapped epitopes.
• Pathogen discrimination: Detects pathogen-specific epitopes, including 30 HSV2-specific epitopes that are specific against HSV1.

Scientific Applications:

• Immune repertoire mapping: Characterizes antibody epitope specificities within individual sera and across cohorts to profile humoral responses.
• Vaccine antigen discovery: Prioritizes antigenic epitopes across proteomes for vaccine development.
• Serodiagnostics and biomarker discovery: Identifies pathogen- and disease-specific epitopes to inform diagnostic assay and biomarker development.
• Pathogen-specific discrimination: Enables discrimination of closely related pathogens through species- or strain-specific epitope identification (e.g., HSV2 versus HSV1).

Methodology:

Use next-generation sequencing data from randomly selected antibody-binding peptides across 273 sera; tile candidate antigen sequences into overlapping k-mers and compute k-mer enrichment relative to background to identify putative epitopes.