title: Functional census of mutation sequence spaces: the example of p53 cancer rescue mutants.
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).
authors.affiliation: University of California, Irvine, CA 92697-3435, USA. sdanzige@uci.edu
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Danziger
authors.forename: S Joshua
authors.initials: SJ
authors.lastname: Swamidass
authors.forename: Jue
authors.initials: J
authors.lastname: Zeng
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Dearth
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Chen
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
authors.forename: Vinh P
authors.initials: VP
authors.lastname: Hoang
authors.forename: Hiroto
authors.initials: H
authors.lastname: Saigo
authors.forename: Ray
authors.initials: R
authors.lastname: Luo
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.forename: Rainer K
authors.initials: RK
authors.lastname: Brachmann
authors.forename: Richard H
authors.initials: RH
authors.lastname: Lathrop
mesh_terms: 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*
chemical_list: D016159:Tumor Suppressor Protein p53