Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.

Prediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory in...

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Main Authors: R Geetha Ramani, Shomona Gracia Jacob
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3572112?pdf=render
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author R Geetha Ramani
Shomona Gracia Jacob
author_facet R Geetha Ramani
Shomona Gracia Jacob
author_sort R Geetha Ramani
collection DOAJ
description Prediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory investigations are more often laborious and resource intensive but computational techniques could well surmount these drawbacks. In view of this, we formulated a novel approach utilizing computational techniques to predict the transcriptional activity of multiple site (one-site to five-site) p53 mutants. The optimal MCC obtained by the proposed approach on prediction of one-site, two-site, three-site, four-site and five-site mutants were 0.775,0.341,0.784,0.916 and 0.655 respectively, the highest reported thus far in literature. We have also demonstrated that 2D and 3D features generate higher prediction accuracy of p53 activity and our findings revealed the optimal results for prediction of p53 status, reported till date. We believe detection of the secondary site mutations that suppress tumor growth may facilitate better understanding of the relationship between p53 structure and function and further knowledge on the molecular mechanisms and biological activity of p53, a targeted source for cancer therapy. We expect that our prediction methods and reported results may provide useful insights on p53 functional mechanisms and generate more avenues for utilizing computational techniques in biological data analysis.
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spelling doaj.art-01cc3fdcaff04fd68986ea7e6ac59f872022-12-21T19:10:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5540110.1371/journal.pone.0055401Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.R Geetha RamaniShomona Gracia JacobPrediction of secondary site mutations that reinstate mutated p53 to normalcy has been the focus of intense research in the recent past owing to the fact that p53 mutants have been implicated in more than half of all human cancers and restoration of p53 causes tumor regression. However laboratory investigations are more often laborious and resource intensive but computational techniques could well surmount these drawbacks. In view of this, we formulated a novel approach utilizing computational techniques to predict the transcriptional activity of multiple site (one-site to five-site) p53 mutants. The optimal MCC obtained by the proposed approach on prediction of one-site, two-site, three-site, four-site and five-site mutants were 0.775,0.341,0.784,0.916 and 0.655 respectively, the highest reported thus far in literature. We have also demonstrated that 2D and 3D features generate higher prediction accuracy of p53 activity and our findings revealed the optimal results for prediction of p53 status, reported till date. We believe detection of the secondary site mutations that suppress tumor growth may facilitate better understanding of the relationship between p53 structure and function and further knowledge on the molecular mechanisms and biological activity of p53, a targeted source for cancer therapy. We expect that our prediction methods and reported results may provide useful insights on p53 functional mechanisms and generate more avenues for utilizing computational techniques in biological data analysis.http://europepmc.org/articles/PMC3572112?pdf=render
spellingShingle R Geetha Ramani
Shomona Gracia Jacob
Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
PLoS ONE
title Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
title_full Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
title_fullStr Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
title_full_unstemmed Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
title_short Prediction of P53 mutants (multiple sites) transcriptional activity based on structural (2D&3D) properties.
title_sort prediction of p53 mutants multiple sites transcriptional activity based on structural 2d 3d properties
url http://europepmc.org/articles/PMC3572112?pdf=render
work_keys_str_mv AT rgeetharamani predictionofp53mutantsmultiplesitestranscriptionalactivitybasedonstructural2d3dproperties
AT shomonagraciajacob predictionofp53mutantsmultiplesitestranscriptionalactivitybasedonstructural2d3dproperties