The epitope space of the human proteome.
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.
Berglund
Lisa
L
School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, SE-106 91 Stockholm, Sweden.
Andrade
Jorge
J
Odeberg
Jacob
J
Uhlén
Mathias
M
D000465:Algorithms; D001666:Binding Sites, Antibody / Q000235:genetics; D018604:Epitope Mapping / Q000379:methods*; D000939:Epitopes / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D020543:Proteome / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012984:Software
D000939:Epitopes; D020543:Proteome