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Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants

  • Author(s): Danziger, S A;
  • Swamidass, S J;
  • Zeng, J;
  • Dearth, L R;
  • Lu, Q;
  • Chen, J H;
  • Cheng, J L;
  • Hoang, V P;
  • Saigo, H;
  • Luo, R;
  • Baldi, P;
  • Brachmann, R K;
  • Lathrop, R H
  • et al.
Abstract

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).

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