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

Samuel A. Danziger, S. Joshua Swamidass, Jue Zeng, Lawrence R. Dearth, Qiang Lu, Jonathan H. Chen, Jianlin Cheng, Vinh P. Hoang, Hiroto Saigo, Ray Luo, Pierre Baldi, Rainer K. Brachmann, Richard H. Lathrop

Research output: Contribution to journalArticle

24 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalIEEE/ACM Transactions on Computational Biology and Bioinformatics
Volume3
Issue number2
DOIs
Publication statusPublished - Apr 1 2006

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Census
Sequence Space
Censuses
Mutant
Cancer
Mutation
Oncology
Neoplasms
Percent
Research
Iteration
HIV
Methodology
Biology

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics
  • Applied Mathematics

Cite this

Danziger, S. A., Swamidass, S. J., Zeng, J., Dearth, L. R., Lu, Q., Chen, J. H., ... Lathrop, R. H. (2006). Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 3(2), 114-124. https://doi.org/10.1109/TCBB.2006.22

Functional census of mutation sequence spaces : The example of p53 cancer rescue mutants. / Danziger, Samuel A.; Swamidass, S. Joshua; Zeng, Jue; Dearth, Lawrence R.; Lu, Qiang; Chen, Jonathan H.; Cheng, Jianlin; Hoang, Vinh P.; Saigo, Hiroto; Luo, Ray; Baldi, Pierre; Brachmann, Rainer K.; Lathrop, Richard H.

In: IEEE/ACM Transactions on Computational Biology and Bioinformatics, Vol. 3, No. 2, 01.04.2006, p. 114-124.

Research output: Contribution to journalArticle

Danziger, SA, Swamidass, SJ, Zeng, J, Dearth, LR, Lu, Q, Chen, JH, Cheng, J, Hoang, VP, Saigo, H, Luo, R, Baldi, P, Brachmann, RK & Lathrop, RH 2006, 'Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants', IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 3, no. 2, pp. 114-124. https://doi.org/10.1109/TCBB.2006.22
Danziger, Samuel A. ; Swamidass, S. Joshua ; Zeng, Jue ; Dearth, Lawrence R. ; Lu, Qiang ; Chen, Jonathan H. ; Cheng, Jianlin ; Hoang, Vinh P. ; Saigo, Hiroto ; Luo, Ray ; Baldi, Pierre ; Brachmann, Rainer K. ; Lathrop, Richard H. / Functional census of mutation sequence spaces : The example of p53 cancer rescue mutants. In: IEEE/ACM Transactions on Computational Biology and Bioinformatics. 2006 ; Vol. 3, No. 2. pp. 114-124.
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