PUBLICATION

Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases

Authors
Wiley, D.J., Juan, I., Le, H., Cai, X., Baumbach, L., Beattie, C., D'Urso, G.
ID
ZDB-PUB-140731-1
Date
2014
Source
F1000Research   3: 121 (Journal)
Registered Authors
Beattie, Christine
Keywords
none
MeSH Terms
none
PubMed
25075304 Full text @ F1000Res
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes