APPRIS

APPRIS annotates splice isoforms and selects a principal isoform per protein-coding gene by integrating protein structural, functional and cross-species conservation evidence to represent the main expressed protein product.

Key Features:

• Principal Isoform Selection: Selects a principal isoform for each protein-coding gene using combined structural, functional and conservation annotations.
• Cross-Species Conservation: Integrates cross-species alignment and conservation evidence to evaluate functional conservation across organisms.
• Protein Structural and Functional Annotations: Annotates splice isoforms with protein structural information, functionally important residues and conserved domains.
• Integration of Multiple Datasets: Includes data for human, chimpanzee, Drosophila melanogaster, Caenorhabditis elegans, cow and chicken and covers the RefSeq gene set and the UniProtKB proteome for six species.
• TRIFID Functional Isoform Scores: Implements TRIFID functional isoform scores assigned to all splice isoforms to assist principal isoform determination when core methods are limited.
• Proteomics Evidence Integration: Integrates expanded proteomics evidence, particularly for the human genome, including experimental protein studies and clinical variant distributions to support principal isoform relevance.
• Reliability Measures: Provides a reliability measure for individual principal isoforms to indicate annotation confidence.

Scientific Applications:

• Genomic Research: Facilitates interpretation of gene expression and regulation at the protein level by defining a reference principal isoform.
• Disease Studies: Supports analysis of how alternative splicing and variants affect protein function in genetic disease research.
• Evolutionary Biology: Uses cross-species conservation data to study functional conservation and evolutionary relationships.
• Proteomics: Supports proteomics validation by linking predicted principal isoforms to experimental protein evidence.

Methodology:

APPRIS uses an annotation pipeline that integrates protein structural, functional and cross-species conservation data, applies TRIFID functional isoform scores and incorporates proteomics evidence to select principal isoforms and assign reliability measures.