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Journal Article

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

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Swamidass SJ, Zeng J, Dearth LR, Lu Q, Cheng JH, Cheng JL, Hoang VP, Saigo, H
Department Empirical Inference, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Citation

Danziger, S., Swamidass SJ, Zeng J, Dearth LR, Lu Q, Cheng JH, Cheng JL, Hoang VP, Saigo, H., Luo R, Baldi P, Brachmann, R., & Lathrop, R. (2006). Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants. IEEE Transactions on Computational Biology and Bioinformatics, 3(2), 114-125. doi:10.1109/TCBB.2006.22.

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).