The APPRIS system (Figure 1) is composed of eight separate annotation modules. These eight modules do not comprise an exhaustive list of all possible protein features. Instead, the methods used in APPRIS were chosen for their ability to select principal isoforms. Each method either detects the absence of highly conserved protein features (as highly conserved protein features are extremely unlikely to have arisen by chance, we can discard variants that lack these features) or calculates cross-species conservation (the more conserved an exon/transcript, the more likely that it represents the principal variant). None of the computational methods behind each module is previously unpublished. Instead, the methods have either been combined in novel ways or have been adjusted especially for APPRIS, and the output of all the methods has been tuned to keep false-positive predictions to a minimum, albeit at the expense of coverage.
