Molecular classification of scrapie strains in mice using gene expression profiling.
Transmissible spongiform encephalopathy strains demonstrate specific prion characteristics, each with specific incubation times, and strain-specific patterns of deposition of the misfolded isoform of prion, PrPSc, in the brains of infected individuals. Different biochemical properties, including glycosylation profiles and the degree of proteinase resistance, have been shown to be strain-specific. However, no relationship between these properties and the phenotypic differences in the subsequent diseases has as yet been determined. Here we explore the utility of gene expression profiles to identify differences in the host response to different strains of prion agent. We identify 114 genes that exhibit significantly different levels of expression in mice infected with three strains of scrapie. These genes represent a pool of genes involved in a strain-specific response to prion disease. We have identified the most discriminatory genes from this list utilizing a wrapper-based feature selection algorithm with external cross-validation.
Booth
Stephanie
S
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, 1015 Arlington Street, Health Canada, Winnipeg, Man., Canada. Stephanie_Booth@hc-sc.gc.ca
Bowman
Christopher
C
Baumgartner
Richard
R
Dolenko
Brion
B
Sorensen
Garrett
G
Robertson
Catherine
C
Coulthart
Michael
M
Phillipson
Clark
C
Somorjai
Rajmund
R
D000465:Algorithms; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015203:Reproducibility of Results; D012608:Scrapie / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D009419:Nerve Tissue Proteins