Classification of signatures of Bovine Spongiform Encephalopathy in serum using infrared spectroscopy

Abstract

Signatures of Bovine Spongiform Encephalopathy (BSE) have been identified in serum by means of ''Diagnostic Pattern Recognition (DPR)''. For DPR-analysis, mid-infrared spectroscopy of dried films of 641 serum samples was performed using disposable silicon sample carriers and a semi-automated DPR research system operating at room temperature. The combination of four mathematical classification approaches (principal component analysis plus linear discriminant analysis, robust linear discriminant analysis, artificial neural network, support vector machine) allowed for a reliable assignment of spectra to the class ''BSEpositive'' or ''BSE-negative''. An independent, blinded validation study was carried out on a second DPR research system at the Veterinary Laboratory Agency, Weybridge, UK. Out of 84 serum samples originating from terminally-ill, BSE-positive cattle, 78 were classified correctly. Similarly, 73 out of 76 BSE-negative samples were correctly identified by DPR such that, numerically, an accuracy of 94.4 % can be calculated. At a confidence level of 0.95 (a~0.05) these results correspond to a sensitivity w 85% and a specificity w 90%. Identical class assignment by all four classifiers occurred in 75% of the cases while ambiguous results were obtained in only 8 of the 160 cases. With an area under the ROC (receiver operating charateristics) curve of 0.991, DPR may potentially supply a valuable surrogate marker for BSE even in cases in which a deliberate bias towards improved sensitivity or specificity is desired. To the best of our knowledge, DPR is the first andup to now-only method which has demonstrated its capability of detecting BSE-related signatures in serum.

Disease recognition by infrared and Raman spectroscopy

“…The idea is to combine the predictions of a number of different classifiers into a new prediction. LDA, PCA-based LDA, SVM and ANN were averaged to obtain a classification result for BSE by IR spectra of serum [51]. Another way to form an ensemble of models for aggregation uses the same method, but with slight variations of training data.…”

“…Prion disease was identified antemortem in bovine spongiform encephalopathy (BSE) infected cattle [51,68] and hamsters [47,48] by a combination of IR spectra from sera and advanced methods of pattern recognition. The experimental findings indicated the presence of distinct surrogate markers in the sera rather than the direct detection of the pathological prion protein.…”

“…SVM enlarge the feature space so that nonlinear class boundaries (in the original feature space) can be modeled. SVM were applied as a member of ensemble methods for the identification of bovine spongiform encephalopathy by IR spectra of serum [51].…”

LS-SVM: uma nova ferramenta quimiométrica para regressão multivariada. Comparação de modelos de regressão LS-SVM e PLS na quantificação de adulterantes em leite em pó empregando NIR

“…Para as misturas ternárias foi realizado um planejamento com 6 níveis de concentração (4,8,12,15, 20 e 25%), conforme Tabela 1, com o propósito de ter amostras com concentrações igualmente espaçadas em toda a faixa estudada para cada um dos contaminantes.…”

Metabolic Fingerprinting of Biofluids by Infrared Spectroscopy: Modeling and Optimization of Flow Rates for Laminar Fluid Diffusion Interface Sample Preconditioning

“…Today's IR spectrometers and microspectrometers are stable and sensitive enough to usefully characterize complex biological fluids and tissues, serving both as biomedical research tools and potentially as clinical devices. 1-3 For example, we and others have developed IR-based analytical methods to simultaneously quantify a number of clinically relevant analytes in blood, serum, and urine, 4-11 with parallel efforts on diagnostic test development, [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] including metabolic fingerprinting [28][29][30] applications ranging from diabetes 18-21 to mad cow disease. [23][24][25][26][27] The spectroscopic methods most commonly associated with emerging metabolomics applications are NMR spectroscopy [31][32][33][34][35][36][37][38][39][40] * Corresponding author.…”