Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants
Published Web Locationhttp://ieeexplore.ieee.org/iel5/8857/34219/01631993.pdf?isnumber=34219∏=JNL&arnumber=1631993&arSt=+114&ared=+125&arAuthor=+Danziger%2C+S.A.%3B++Swamidass%2C+S.J.%3B++Jue+Zeng%3B++Dearth%2C+L.R.%3B++Qiang+Lu%3B++Chen%2C+J.H.%3B++Jianlin+Cheng%3B++Hoang%2C+V.P.%3B++Saigo%2C+H.%3B++Luo%2C+R.%3B++Baldi%2C+P.%3B++Brachmann%2C+R.K.%3B++Lathrop%2C+R.H.
Many biomedical problems relate to mutant functional properties across a sequence space of interest, e. g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 mutant rescue. We devised a general methodology for conducting a functional census of a mutation sequence space by choosing informative mutants early. The methodology was tested in a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of three ( 24 iterations). The first double-blind 15-point moving accuracy was 47 percent and the last was 86 percent; r = 0.01 before an epiphanic 16th iteration and r = 0.92 afterward. Useful mutants were chosen early ( overall r = 0.80). Code and data are freely available (http://www.igb.uci.edu/research/research.html, corresponding authors: R. H. L. for computation and R. K. B. for biology).