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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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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. |
format | Online Article Text |
id | pubmed-3809358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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