A systems approach to prion disease

Daehee Hwang, Inyoul Y. Lee, Hyuntae Yoo, Nils Gehlenborg, Ji Hoon Cho, Brianne Petritis, David Baxter, Rose Pitstick, Rebecca Young, Doug Spicer, Nathan D. Price, John G. Hohmann, Stephen J. DeArmond, George A. Carlson, Leroy E. Hood

Research output: Contribution to journalArticlepeer-review

Abstract

Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrP C) to disease-causing PrPSc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain-prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrPSc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches.

Original languageEnglish (US)
Article number252
JournalMolecular systems biology
Volume5
DOIs
StatePublished - Jan 20 2009
Externally publishedYes

Keywords

  • Microarray
  • Network analysis
  • Neurodegenerative disease
  • Prion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Fingerprint Dive into the research topics of 'A systems approach to prion disease'. Together they form a unique fingerprint.

Cite this