The exemplified methods and systems facilitate the configuration and training of a neural network (e.g., a deep neural network, a convolutional neural network (CNN), etc.), or ensemble(s) thereof, with a biophysical signal data set to ascertain estimate for the presence or non-presence of disease or pathology in a subject as well as to assess and/or classify disease or pathology, including for example in some cases the severity of such disease or pathology, in a subject. In the context of the heart, the methods and systems described herein facilitate the configuration and training of a neural network, or ensemble(s) thereof, with a cardiac signal data set to ascertain estimate for the presence or non-presence of coronary artery disease or coronary pathology.