title: Factors affecting the accuracy of urine-based biomarkers of BSE.
abstract: BACKGROUND
  Transmissible spongiform encephalopathy diseases are untreatable, uniformly fatal degenerative syndromes of the central nervous system that can be transmitted both within as well as between species. The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob disease (vCJD), have profoundly influenced beef production processes as well as blood donation and surgical procedures. Simple, robust and cost effective diagnostic screening and surveillance tools are needed for both the preclinical and clinical stages of TSE disease in order to minimize both the economic costs and zoonotic risk of BSE and to further reduce the risk of secondary vCJD.
  
  
  OBJECTIVE
  Urine is well suited as the matrix for an ante-mortem test for TSE diseases because it would permit non-invasive and repeated sampling. In this study urine samples collected from BSE infected and age matched control cattle were screened for the presence of individual proteins that exhibited disease specific changes in abundance in response to BSE infection that might form the basis of such an ante-mortem test.
  
  
  RESULTS
  Two-dimensional differential gel electrophoresis (2D-DIGE) was used to identify proteins exhibiting differential abundance in two sets of cattle. The known set consisted of BSE infected steers and age matched controls throughout the course of the disease. The blinded unknown set was composed of BSE infected and control samples of both genders, a wide range of ages and two different breeds. Multivariate analyses of individual protein abundance data generated classifiers comprised of the proteins best able to discriminate between the samples based on disease state, breed, age and gender.
  
  
  CONCLUSIONS
  Despite the presence of confounding factors, the disease specific changes in abundance exhibited by a panel of urine proteins permitted the creation of classifiers able to discriminate between control and infected cattle with a high degree of accuracy.
authors.affiliation: Prion Diseases Program, Public Health Agency of Canada, Winnipeg, R3E 3P6, Canada. David.Knox@phac-aspc.gc.ca.
authors.forename: Margot
authors.initials: M
authors.lastname: Plews
authors.forename: Lise
authors.initials: L
authors.lastname: Lamoureux
authors.forename: Sharon Lr
authors.initials: SL
authors.lastname: Simon
authors.forename: Catherine
authors.initials: C
authors.lastname: Graham
authors.forename: Viola
authors.initials: V
authors.lastname: Ruddat
authors.forename: Stefanie
authors.initials: S
authors.lastname: Czub
authors.forename: J David
authors.initials: JD
authors.lastname: Knox