ProtMapper

ProtMapper normalizes phosphosite positions to human UniProt reference sequences to enable accurate integration of phosphoproteomic datasets and upstream regulatory annotations.

Key Features:

• Python implementation: Implemented in Python for programmatic mapping and normalization of phosphosite annotations.
• Phosphosite normalization: Maps amino acid sites of post-translational modifications from models or experimental data to human reference positions.
• Non-canonical site resolution: Resolves discrepancies arising from non-human proteins (e.g., mouse or rat), alternative isoforms, and post-translationally processed variants.
• Database-guided mapping: Uses UniProt and PhosphoSitePlus site groups supplemented with manual curation to align sites to reference sequences.
• Knowledge integration: Integrates with INDRA and text-mined annotations to assemble regulatory information for phosphosites.
• Mass spectrometry support: Applied to large-scale mass spectrometry datasets such as CPTAC to normalize site annotations.

Scientific Applications:

• Phosphoproteomic data standardization: Standardizes phosphosite annotations across datasets to support downstream computational and statistical analyses.
• Regulatory annotation assembly: In conjunction with INDRA, was used to compile 37,028 regulatory annotations for 16,332 phosphosites.
• Integration of curated and literature-derived knowledge: Facilitates merging of curated database entries and literature-extracted statements into a cohesive knowledge base.
• Upstream regulator mapping: Enables more reliable identification and analysis of upstream regulators of phosphorylation sites.

Methodology:

Maps amino acid sites to UniProt reference sequences using PhosphoSitePlus site groups and manual curation, resolves non-canonical numbering from non-human proteins, isoforms, or processed variants, and integrates text-mined statements via the INDRA knowledge assembly system.