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

5 Citations (Scopus)

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
Article number4188.1
JournalF1000Research
Volume3
DOIs
StatePublished - Jun 2 2014

Fingerprint

Inborn Genetic Diseases
Medical Genetics
Electric network analysis
Systems Analysis
Spinal Muscular Atrophy
Yeast
Schizosaccharomyces
Yeasts
Genes
Protein Interaction Maps
Gene Regulatory Networks
Zebrafish
Muscular Diseases
Therapeutics
Vertebrates
Proteins
Throughput
Databases

ASJC Scopus subject areas

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

Cite this

Yeast Augmented Network Analysis (YANA) : A new systems approach to identify therapeutic targets for human genetic diseases. / D'urso, Gennaro; Wiley, David J.; Juan, Ilona; Le, Hao; Cai, Xiaodong; Baumbach, Lisa; Beattie, Christine.

In: F1000Research, Vol. 3, 4188.1, 02.06.2014.

Research output: Contribution to journalArticle

@article{25ee54ee737d433e9b4bbc417766581b,
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.",
author = "Gennaro D'urso and Wiley, {David J.} and Ilona Juan and Hao Le and Xiaodong Cai and Lisa Baumbach and Christine Beattie",
year = "2014",
month = "6",
day = "2",
doi = "10.12688/f1000research.4188.1",
language = "English",
volume = "3",
journal = "F1000Research",
issn = "2046-1402",
publisher = "F1000 Research Ltd.",

}

TY - JOUR

T1 - Yeast Augmented Network Analysis (YANA)

T2 - A new systems approach to identify therapeutic targets for human genetic diseases

AU - D'urso, Gennaro

AU - Wiley, David J.

AU - Juan, Ilona

AU - Le, Hao

AU - Cai, Xiaodong

AU - Baumbach, Lisa

AU - Beattie, Christine

PY - 2014/6/2

Y1 - 2014/6/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84914812205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84914812205&partnerID=8YFLogxK

U2 - 10.12688/f1000research.4188.1

DO - 10.12688/f1000research.4188.1

M3 - Article

AN - SCOPUS:84914812205

VL - 3

JO - F1000Research

JF - F1000Research

SN - 2046-1402

M1 - 4188.1

ER -