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APPRIS (https://appris.bioinfo.cnio.es) is a well-established database housing annotations for protein isoforms for a range of species. APPRIS selects principal isoforms based on protein structure and function features and on cross-species conservation. Most coding genes produce a single main protein isoform and the principal isoforms chosen by the APPRIS database best represent this main cellular isoform. Human genetic data, experimental protein evidence and the distribution of clinical variants all support the relevance of APPRIS principal isoforms. APPRIS annotations and principal isoforms have now been expanded to 10 model organisms. In this paper we highlight the most recent updates to the database. APPRIS annotations have been generated for two new species, cow and chicken, the protein structural information has been augmented with reliable models from the EMBL-EBI AlphaFold database, and we have substantially expanded the confirmatory proteomics evidence available for the human genome. The most significant change in APPRIS has been the implementation of TRIFID functional isoform scores. TRIFID functional scores are assigned to all splice isoforms, and APPRIS uses the TRIFID functional scores and proteomics evidence to determine principal isoforms when core methods cannot.

The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the 'principal' isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants.

This paper introduces the APPRIS WebServer (http://appris.bioinfo.cnio.es) and WebServices (http://apprisws.bioinfo.cnio.es). Both the web servers and the web services are based around the APPRIS Database, a database that presently houses annotations of splice isoforms for five different vertebrate genomes. The APPRIS WebServer and WebServices provide access to the computational methods implemented in the APPRIS Database, while the APPRIS WebServices also allows retrieval of the annotations. The APPRIS WebServer and WebServices annotate splice isoforms with protein structural and functional features, and with data from cross-species alignments. In addition they can use the annotations of structure, function and conservation to select a single reference isoform for each protein-coding gene (the principal protein isoform). APPRIS principal isoforms have been shown to agree overwhelmingly with the main protein isoform detected in proteomics experiments. The APPRIS WebServer allows for the annotation of splice isoforms for individual genes, and provides a range of visual representations and tools to allow researchers to identify the likely effect of splicing events. The APPRIS WebServices permit users to generate annotations automatically in high throughput mode and to interrogate the annotations in the APPRIS Database. The APPRIS WebServices have been implemented using REST architecture to be flexible, modular and automatic. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Here, we present APPRIS (http://appris.bioinfo.cnio.es), a database that houses annotations of human splice isoforms. APPRIS has been designed to provide value to manual annotations of the human genome by adding reliable protein structural and functional data and information from cross-species conservation. The visual representation of the annotations provided by APPRIS for each gene allows annotators and researchers alike to easily identify functional changes brought about by splicing events. In addition to collecting, integrating and analyzing reliable predictions of the effect of splicing events, APPRIS also selects a single reference sequence for each gene, here termed the principal isoform, based on the annotations of structure, function and conservation for each transcript. APPRIS identifies a principal isoform for 85% of the protein-coding genes in the GENCODE 7 release for ENSEMBL. Analysis of the APPRIS data shows that at least 70% of the alternative (non-principal) variants would lose important functional or structural information relative to the principal isoform.