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

Gennaro D'Urso, David J. Wiley, Ilona Juan, Hao Le, Xiaodong Cai, Lisa Baumbach, Christine Beattie

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article number4188.1
JournalF1000Research
Volume3
DOIs
StatePublished - Jun 2 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Yeast Augmented Network Analysis (YANA): A new systems approach to identify therapeutic targets for human genetic diseases'. Together they form a unique fingerprint.

  • Cite this