Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk]
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...
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doaj-593dfbbc94c5478fa467eeba0756e52f2020-11-25T03:10:21ZengF1000 Research LtdF1000Research2046-14022014-06-01310.12688/f1000research.4188.14484Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk]David J. Wiley0Ilona Juan1Hao Le2Xiaodong Cai3Lisa Baumbach4Christine Beattie5Gennaro D'Urso6Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USADepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USADepartment of Neuroscience, Ohio State University, Columbus, OH, 43210, USADepartment of Engineering, University of Miami, Miami, FL, 33124, USAIntegrated Functional Cancer Genomics, TGEN, Phoenix, AZ, 85004, USADepartment of Neuroscience, Ohio State University, Columbus, OH, 43210, USADepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USAGenetic 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.http://f1000research.com/articles/3-121/v1GenomicsMedical GeneticsMethods for Diagnostic & Therapeutic Studies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David J. Wiley Ilona Juan Hao Le Xiaodong Cai Lisa Baumbach Christine Beattie Gennaro D'Urso |
spellingShingle |
David J. Wiley Ilona Juan Hao Le Xiaodong Cai Lisa Baumbach Christine Beattie Gennaro D'Urso Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] F1000Research Genomics Medical Genetics Methods for Diagnostic & Therapeutic Studies |
author_facet |
David J. Wiley Ilona Juan Hao Le Xiaodong Cai Lisa Baumbach Christine Beattie Gennaro D'Urso |
author_sort |
David J. Wiley |
title |
Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
title_short |
Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
title_full |
Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
title_fullStr |
Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
title_full_unstemmed |
Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
title_sort |
yeast augmented network analysis (yana): a new systems approach to identify therapeutic targets for human genetic diseases [v1; ref status: indexed, http://f1000r.es/3gk] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2014-06-01 |
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. |
topic |
Genomics Medical Genetics Methods for Diagnostic & Therapeutic Studies |
url |
http://f1000research.com/articles/3-121/v1 |
work_keys_str_mv |
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