APPRIS has been developed within the GENCODE consortium (14) to annotate alternative gene products with reliable, biologically relevant data. GENCODE provides high-accuracy manual annotations of protein-coding loci and alternative variants as part of the ENCODE project (12,15). The GENCODE annotations are gradually replacing and augmenting the Ensembl (16) automatic annotations. As part of the GENCODE annotation process, APPRIS flags isoforms with likely altered structure, function or localization, and exons that are evolving unusually. The information from APPRIS is fed back to the manual annotators and has lead to the annotation of new isoforms.
