4.7 Article

Prion Disease Diagnosis by Proteomic Profiling

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 8, Issue 2, Pages 1030-1036

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/pr800832s

Keywords

biomarkers; prion disease; transmissible spongiform encephalopathy; MALDI-FTMS; machine learning algorithms; support vector machines; proteomics

Funding

  1. National Prion Research Program [DAMD17-03-1-0291]
  2. National Institutes of Health [AI0272588]
  3. Wisconsin Alumni Research Foundation at the University of Wisconsin-Madison
  4. Alfred P. Sloan Research Fellowship

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Definitive prion disease diagnosis is currently limited to postmortem assay for the presence of the disease-associated proteinase K-resistant prion protein. Using cerebrospinal fluid (CSF) from prion-infected hamsters, matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS), and support vector machines (SVM), we have identified peptide profiles characteristic of disease state. Using 10-fold leave-one-out cross-validation, we report a predictive accuracy of 72% with a true positive rate of 73% and a false positive rate of 27% demonstrating the suitability of using proteomic profiling and CSF for the development of multiple marker diagnostics of prion disease.

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