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Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases
Genetic interaction networks that underlie most human diseases are highly complex and poorly defined. Better-defined networks will allow identification of a greater number of therapeutic targets. Here we introduce our Yeast Augmented Network Analysis (YANA) approach and test it with the X-linked spi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
F1000Research
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097366/ https://www.ncbi.nlm.nih.gov/pubmed/25075304 http://dx.doi.org/10.12688/f1000research.4188.1 |
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author | Wiley, David J. Juan, Ilona Le, Hao Cai, Xiaodong Baumbach, Lisa Beattie, Christine D'Urso, Gennaro |
author_facet | Wiley, David J. Juan, Ilona Le, Hao Cai, Xiaodong Baumbach, Lisa Beattie, Christine D'Urso, Gennaro |
author_sort | Wiley, David J. |
collection | PubMed |
description | Genetic interaction networks that underlie most human diseases are highly complex and poorly defined. Better-defined networks will allow identification of a greater number of therapeutic targets. Here we introduce our Yeast Augmented Network Analysis (YANA) approach and test it with the X-linked spinal muscular atrophy (SMA) disease gene UBA1. First, we express UBA1 and a mutant variant in fission yeast and use high-throughput methods to identify fission yeast genetic modifiers of UBA1. Second, we analyze available protein-protein interaction network databases in both fission yeast and human to construct UBA1 genetic networks. Third, from these networks we identified potential therapeutic targets for SMA. Finally, we validate one of these targets in a vertebrate (zebrafish) SMA model. This study demonstrates the power of combining synthetic and chemical genetics with a simple model system to identify human disease gene networks that can be exploited for treating human diseases. |
format | Online Article Text |
id | pubmed-4097366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | F1000Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-40973662014-07-28 Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases Wiley, David J. Juan, Ilona Le, Hao Cai, Xiaodong Baumbach, Lisa Beattie, Christine D'Urso, Gennaro F1000Res Research Article Genetic interaction networks that underlie most human diseases are highly complex and poorly defined. Better-defined networks will allow identification of a greater number of therapeutic targets. Here we introduce our Yeast Augmented Network Analysis (YANA) approach and test it with the X-linked spinal muscular atrophy (SMA) disease gene UBA1. First, we express UBA1 and a mutant variant in fission yeast and use high-throughput methods to identify fission yeast genetic modifiers of UBA1. Second, we analyze available protein-protein interaction network databases in both fission yeast and human to construct UBA1 genetic networks. Third, from these networks we identified potential therapeutic targets for SMA. Finally, we validate one of these targets in a vertebrate (zebrafish) SMA model. This study demonstrates the power of combining synthetic and chemical genetics with a simple model system to identify human disease gene networks that can be exploited for treating human diseases. F1000Research 2014-06-02 /pmc/articles/PMC4097366/ /pubmed/25075304 http://dx.doi.org/10.12688/f1000research.4188.1 Text en Copyright: © 2014 Wiley DJ et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/publicdomain/zero/1.0/ Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). |
spellingShingle | Research Article Wiley, David J. Juan, Ilona Le, Hao Cai, Xiaodong Baumbach, Lisa Beattie, Christine D'Urso, Gennaro Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title | Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title_full | Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title_fullStr | Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title_full_unstemmed | Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title_short | Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases |
title_sort | yeast augmented network analysis (yana): a new systems approach to identify therapeutic targets for human genetic diseases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097366/ https://www.ncbi.nlm.nih.gov/pubmed/25075304 http://dx.doi.org/10.12688/f1000research.4188.1 |
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