Genomics 2 Proteins portal

Genomics 2 Proteins portal maps genetic variants onto PDB and AlphaFold-derived protein structures to integrate structural and functional annotations for interpreting variant effects and informing disease-mechanism and therapeutic hypotheses.

Key Features:

• Variant mapping: Maps genetic variants onto Protein Data Bank (PDB) and AlphaFold-derived structures and accepts uploaded variant lists and residue-wise annotations.
• Structural and functional overlays: Integrates UniProt domains, post-translational modifications (PTMs), disorder regions, conservation data, and public variant tracks (ClinVar, gnomAD, HGMD) onto structures.
• 3D hotspot identification: Detects and highlights three-dimensional hotspots within protein structures.
• Export formats: Exports combined TSV files and initiates PyMOL sessions for downstream structural analysis.
• REST API: Provides a RESTful API for batch processing and integration into automated workflows.
• Proteome-scale coverage: Maps over 20 million genetic variants across 42,413 protein sequences and 77,923 structures.

Scientific Applications:

• Variant effect interpretation: Relates genomic variants to structural context to assess potential impacts on protein function and molecular phenotype.
• Disease-mechanism hypothesis generation: Supports formulation of hypotheses linking natural or synthetic variations to disease mechanisms based on structural and functional annotations.
• Therapeutic target and design support: Informs identification of critical structural regions and hotspots relevant to therapeutic targeting and design.

Methodology:

Maps variants onto PDB and AlphaFold structures; overlays UniProt domains, PTMs, disorder regions, conservation data, and public variant tracks (ClinVar, gnomAD, HGMD); identifies three-dimensional hotspots; exports combined TSV and PyMOL sessions; and exposes a RESTful API for batch processing.