Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants |
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Authors: | Danziger Samuel A Swamidass S Joshua Zeng Jue Dearth Lawrence R Lu Qiang Chen Jonathan H Cheng Jianlin Hoang Vinh P Saigo Hiroto Luo Ray Baldi Pierre Brachmann Rainer K Lathrop Richard H |
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Institution: | California Univ., Irvine, CA, USA; |
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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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