HoTIDP

HoTIDP transfers annotations by homology to extend DisProt experimentally supported disorder-state and functional annotations to orthologous intrinsically disordered proteins (IDPs) across species.

Key Features:

• Annotation Transfer: Transfers experimentally supported and manually curated disorder-state and functional annotations from DisProt to orthologous proteins.
• Homology-Based Approach: Infers shared function via orthology to extrapolate DisProt annotations to homologs.
• Multiple Sequence Alignments (MSAs): Generates MSAs between a protein and its orthologs and applies rigorous alignment quality control to address rapid evolution of disordered regions.
• Beyond Globular Domains: Enables annotation transfer for intrinsically disordered regions as well as non-globular portions of proteins.
• Scalability and Results: Applied to 1,731 DisProt entries with 5,623 annotations, extending annotations to 97,555 orthologs and transferring 301,190 terms by homology.

Scientific Applications:

• IDP Annotation Expansion: Populate disorder-state and functional annotations for orthologs of DisProt entries to increase annotation coverage of IDPs.
• Evolutionary Analysis: Assess conservation and divergence of disordered regions and their functions across species using transferred annotations.
• Disease and Therapeutics Research: Provide functional hypotheses for IDPs that can inform investigations of disease mechanisms and potential therapeutic targets.

Methodology:

Identify orthologs for each DisProt entry, generate MSAs with stringent quality controls, and map DisProt annotations to orthologous sequences by homology.