is the identification of a molecular or cellular phenotype that correlates with the disease state. In many cases, this can be identified through global gene expression profiling of patient and control samples (at the RNA or protein level), and identification of a profile of gene expression changes that correlate with disease. Alternatively, other cellular phenotypes can be employed such as functional readouts of cell activity (e.g. electrophysiological measurements of neurons, activity of cardiac muscle or response of macrophages to pathogen stimulation), more generic cellular features such as cell shape, subcellular localisation of particular marker genes, endocytic trafficking, or cellular responses to their environment (e.g. secretion or response to signals, sensitivity to drugs or other cellular stresses). In some cases, such as mutations in SCN5A that are linked to cardiac arrhythmia and long QT syndrome, these phenotypes are predictable and directly related to the disease (Davis et al. 2012). However, in other diseases such as autism spectrum disorders (ASD) (DeRosa et al. 2012) or schizophrenia (Brennand et al. 2011) which are classified by complex behavioural phenotypes, how well these correlate to any underlying molecular or cellular changes, and to what extent these are causative in the disease are still largely unexplored.
