TY - JOUR
T1 - Functional census of mutation sequence spaces
T2 - The example of p53 cancer rescue mutants
AU - Danziger, Samuel A.
AU - Swamidass, S. Joshua
AU - Zeng, Jue
AU - Dearth, Lawrence R.
AU - Lu, Qiang
AU - Chen, Jonathan H.
AU - Cheng, Jianlin
AU - Hoang, Vinh P.
AU - Saigo, Hiroto
AU - Luo, Ray
AU - Baldi, Pierre
AU - Brachmann, Rainer K.
AU - Lathrop, Richard H.
N1 - Funding Information:
The authors thank Richard Chamberlin, Melanie Cocco, Richard Colman, John Coroneus, Hartmut Luecke, Don Senear, and Ying Wang for contributions to the larger collaborative p53 functional rescue project. Thanks to the University of California Irvine (UCI) office of Research and Graduate Studies and the UCI Institute for Genomics and Bioinformatics for financial support. Work supported in part by US National Institutes of Health (NIH) Biomedical Informatics Training grant (LM-07443-01), US National Science Foundation (NSF) MRI grant (EIA-0321390) to Pierre Baldi, NIH BISTI grant (CA-112560) and NSF ITR grant (0326037) to Richard H. Lathrop, NIH grant (CA81511) to Rainer K. Brachmann, Harvey Fellowship to S. Joshua Swamidass, and the UCI Medical Scientist Training Program.
PY - 2006/4
Y1 - 2006/4
N2 - 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).
AB - 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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U2 - 10.1109/TCBB.2006.22
DO - 10.1109/TCBB.2006.22
M3 - Article
C2 - 17048398
AN - SCOPUS:33646752804
SN - 1545-5963
VL - 3
SP - 114
EP - 124
JO - IEEE/ACM Transactions on Computational Biology and Bioinformatics
JF - IEEE/ACM Transactions on Computational Biology and Bioinformatics
IS - 2
ER -
