title: Yeast Augmented Network Analysis (YANA): a new systems approach to identify therapeutic targets for human genetic diseases.
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.
authors: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: David J
authors: DJ
authors: Wiley
authors: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: Ilona
authors: I
authors: Juan
authors: Department of Neuroscience, Ohio State University, Columbus, OH, 43210, USA.
authors: Hao
authors: H
authors: Le
authors: Department of Engineering, University of Miami, Miami, FL, 33124, USA.
authors: Xiaodong
authors: X
authors: Cai
authors: Integrated Functional Cancer Genomics, TGEN, Phoenix, AZ, 85004, USA.
authors: Lisa
authors: L
authors: Baumbach
authors: Department of Neuroscience, Ohio State University, Columbus, OH, 43210, USA.
authors: Christine
authors: C
authors: Beattie
authors: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
authors: Gennaro
authors: G
authors: D'Urso