The methods that make up APPRIS detect unusual, missing or non-conserved features and will flag these transcripts as alternative. The selection of a principal isoform is based on a jury of the eight methods that make up the pipeline. The isoform selected as principal will be either the variant that has the most conserved protein features (since it is much more likely that alternative isoforms have lost rather than gained protein features such as 3D structure and function) or that has more evidence of cross-species conservation, or, most frequently, both. Four methods (SPADE, CORSAIR, Matador3D and firestar) make up the core of the jury system, with the other methods becoming more important in cases where these four methods are not able to make a decision.
