Methods and systems are disclosed for classifying mass spectra to discriminate the absence or existence of a condition. The mass spectra may include raw mass spectrum intensity signals or may include intensity signals that have been preprocessed. The method and systems include determining a first or higher order derivative of the signals of the mass spectra, or any linear combination of the signal and a derivative of the signal, to form a mass spectra data set for training a classifier. The mass spectra data set may be provided as input to train a classifier, such as a linear discrimination classifier. The classifier trained with the derivative-based mass spectra data set then classifies mass spectra samples to improve discriminating between the absence or existence of a condition.