Extracting human antibody sequences from public databases for antibody humanization: high frequency of species assignment errors.
In antibody humanization, complementarity determining regions from a 'donor' antibody are often grafted onto a human framework selected by high sequence identity with the donor. In our own humanization experiments, we have found that species information is often incorrect. Here we take three mouse antibodies and perform BLAST searches against sequences annotated as being human. We find that the first genuine human hits for the six chains appear at Positions 30, 4, 11, 24, 18 and 29 in the hit lists. This illustrates both the need for caution in performing humanization and for improvements in annotation.
Institute of Structural and Molecular Biology, Division of Biosciences, Darwin Building, University College London, Gower Street, London WC1E 6BT, UK.
Andrew C R
ACR
Martin
Rees Consulting AB, Näs Focksta 19, Uppsala 75591, Sweden.
Anthony R
AR
Rees
D000595:Amino Acid Sequence; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D019295:Computational Biology; D030562:Databases, Protein; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D012107:Research Design; D013045:Species Specificity
D061067:Antibodies, Monoclonal, Humanized
annotation errors; database searches; sequence databases