Prion disease diagnosis by proteomic profiling.
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.
Herbst
Allen
A
Department of Comparative Biosciences, University of Wisconsin-Madison, Wisconsin 53705-222, USA.
McIlwain
Sean
S
Schmidt
Joshua J
JJ
Aiken
Judd M
JM
Page
C David
CD
Li
Lingjun
L
D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D006224:Cricetinae; D006801:Humans; D017096:Prion Diseases / Q000175:diagnosis*; D011328:Prions / Q000134:cerebrospinal fluid*; D040081:Protein Array Analysis / Q000379:methods / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D011328:Prions