Validation using sensitivity and target transform factor analyses of neural network models for classifying bacteria from mass spectra

Temperature constrained cascade correlation networks (TCCCNs) are computational neural networks that configure their own architecture, train rapidly, and give reproducible prediction results. TCCCN classification models were built using the Latin-partition method for five classes of pathogenic bacteria. Neural networks are problematic in that the relationships among the inputs (i.e., mass spectra) and the outputs (i.e., the bacterial identities) are not apparent. In this study, neural network models were constructed that successfully classified the targeted bacteria and the classification model was validated using sensitivity and target transformation factor analysis (TTFA). Without validation of the classification model, it is impossible to ascertain whether the bacteria are classified by peaks in the mass spectrum that have no causal relationships with the bacteria, but instead randomly correlate with the bacterial classes. Multiple single output network models did not offer any benefits when compared to single network models that had multiple outputs. A multiple output TCCCN model achieved classification accuracies of 96 +/- 2% and exhibited improved performance over multiple single output TCCCN models. Chemical ionization mass spectra were obtained from in situ thermal hydrolysis methylation of freeze-dried bacteria. Mass spectral peaks that pertain to the neural network classification model of the pathogenic bacterial classes were obtained by sensitivity analysis. A significant number of mass spectral peaks that had high sensitivity corresponded to known biomarkers, which is the first time that the significant peaks used by a neural network model to classify mass spectra have been divulged. Furthermore, TTFA furnishes a useful visual target as to which peaks in the mass spectrum correlate with the bacterial identities. (J Am Soc Mass Spectrom 2002,13,10-21) (C) 2002 American Society for Mass Spectrometry.