The Epitope Space of the Human Proteome

Protein Sci. 2008 Apr;17(4):606-13. doi: 10.1110/ps.073347208.

Abstract

In the post-genome era, there is a great need for protein-specific affinity reagents to explore the human proteome. Antibodies are suitable as reagents, but generation of antibodies with low cross-reactivity to other human proteins requires careful selection of antigens. Here we show the results from a proteome-wide effort to map linear epitopes based on uniqueness relative to the entire human proteome. The analysis was based on a sliding window sequence similarity search using short windows (8, 10, and 12 amino acid residues). A comparison of exact string matching (Hamming distance) and a heuristic method (BLAST) was performed, showing that the heuristic method combined with a grid strategy allows for whole proteome analysis with high accuracy and feasible run times. The analysis shows that it is possible to find unique antigens for a majority of the human proteins, with relatively strict rules involving low sequence identity of the possible linear epitopes. The implications for human antibody-based proteomics efforts are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Binding Sites, Antibody / genetics
  • Epitope Mapping / methods*
  • Epitopes / genetics*
  • Genome, Human*
  • Humans
  • Proteome / genetics*
  • Sequence Homology, Amino Acid
  • Software

Substances

  • Epitopes
  • Proteome