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Discriminant analysis of prion sequences for prediction of susceptibility

Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt–Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrP(C)) into abnormal protease-resistant prion protein (PrP(Sc)). There is concern regarding t...

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Autores principales: Lee, Ji-Hae, Bae, Se-Eun, Jung, Sunghoon, Ahn, Insung, Son, Hyeon Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809358/
https://www.ncbi.nlm.nih.gov/pubmed/24113272
http://dx.doi.org/10.1038/emm.2013.100
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author Lee, Ji-Hae
Bae, Se-Eun
Jung, Sunghoon
Ahn, Insung
Son, Hyeon Seok
author_facet Lee, Ji-Hae
Bae, Se-Eun
Jung, Sunghoon
Ahn, Insung
Son, Hyeon Seok
author_sort Lee, Ji-Hae
collection PubMed
description Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt–Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrP(C)) into abnormal protease-resistant prion protein (PrP(Sc)). There is concern regarding these prion diseases because of the possibility of their zoonotic infections across species. Mutations and polymorphisms of prion sequences may influence prion-disease susceptibility through the modified expression and conformation of proteins. Rapid determination of susceptibility based on prion-sequence polymorphism information without complex structural and molecular biological analyses may be possible. Information regarding the effects of mutations and polymorphisms on prion-disease susceptibility was collected based on previous studies to classify the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the position-specific scoring matrix were utilised to determine the distance of target sequences. The k-nearest neighbour analysis was validated with cross-validation methods. The results indicated that the number of polymorphisms did not influence prion-disease susceptibility, and three and four k-objects showed the best accuracy in identifying the susceptible group. Although sequences with negative polymorphisms showed relatively high accuracy for determination, polymorphisms may still not be an appropriate factor for estimating variation in susceptibility. Discriminant analysis of prion sequences with scoring matrices was attempted as a possible means of determining susceptibility to prion diseases. Further research is required to improve the utility of this method.
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spelling pubmed-38093582013-10-28 Discriminant analysis of prion sequences for prediction of susceptibility Lee, Ji-Hae Bae, Se-Eun Jung, Sunghoon Ahn, Insung Son, Hyeon Seok Exp Mol Med Original Article Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt–Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrP(C)) into abnormal protease-resistant prion protein (PrP(Sc)). There is concern regarding these prion diseases because of the possibility of their zoonotic infections across species. Mutations and polymorphisms of prion sequences may influence prion-disease susceptibility through the modified expression and conformation of proteins. Rapid determination of susceptibility based on prion-sequence polymorphism information without complex structural and molecular biological analyses may be possible. Information regarding the effects of mutations and polymorphisms on prion-disease susceptibility was collected based on previous studies to classify the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the position-specific scoring matrix were utilised to determine the distance of target sequences. The k-nearest neighbour analysis was validated with cross-validation methods. The results indicated that the number of polymorphisms did not influence prion-disease susceptibility, and three and four k-objects showed the best accuracy in identifying the susceptible group. Although sequences with negative polymorphisms showed relatively high accuracy for determination, polymorphisms may still not be an appropriate factor for estimating variation in susceptibility. Discriminant analysis of prion sequences with scoring matrices was attempted as a possible means of determining susceptibility to prion diseases. Further research is required to improve the utility of this method. Nature Publishing Group 2013-10 2013-10-11 /pmc/articles/PMC3809358/ /pubmed/24113272 http://dx.doi.org/10.1038/emm.2013.100 Text en Copyright © 2013 KSBMB. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Lee, Ji-Hae
Bae, Se-Eun
Jung, Sunghoon
Ahn, Insung
Son, Hyeon Seok
Discriminant analysis of prion sequences for prediction of susceptibility
title Discriminant analysis of prion sequences for prediction of susceptibility
title_full Discriminant analysis of prion sequences for prediction of susceptibility
title_fullStr Discriminant analysis of prion sequences for prediction of susceptibility
title_full_unstemmed Discriminant analysis of prion sequences for prediction of susceptibility
title_short Discriminant analysis of prion sequences for prediction of susceptibility
title_sort discriminant analysis of prion sequences for prediction of susceptibility
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809358/
https://www.ncbi.nlm.nih.gov/pubmed/24113272
http://dx.doi.org/10.1038/emm.2013.100
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