Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants.
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).
Danziger
Samuel A
SA
University of California, Irvine, CA 92697-3435, USA. sdanzige@uci.edu
Swamidass
S Joshua
SJ
Zeng
Jue
J
Dearth
Lawrence R
LR
Lu
Qiang
Q
Chen
Jonathan H
JH
Cheng
Jianlin
J
Hoang
Vinh P
VP
Saigo
Hiroto
H
Luo
Ray
R
Baldi
Pierre
P
Brachmann
Rainer K
RK
Lathrop
Richard H
RH
D001185:Artificial Intelligence; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D020407:Internet; D008958:Models, Molecular; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D013489:Suppression, Genetic / Q000235:genetics / Q000502:physiology; D013499:Surface Properties; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*
D016159:Tumor Suppressor Protein p53