Journal
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
Volume 3, Issue 2, Pages 114-125Publisher
IEEE COMPUTER SOC
DOI: 10.1109/TCBB.2006.22
Keywords
biology and genetics; feature extraction or construction; machine learning; medicine and science
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Funding
- NCI NIH HHS [R01 CA081511, R01 CA112560, CA-112560, R01 CA112560-01A1, CA81511] Funding Source: Medline
- NLM NIH HHS [LM-07443-01, T15 LM007443] Funding Source: Medline
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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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