Consistency and variation of protein subcellular location annotations

Area of Science:

• Proteomics
• Bioinformatics
• Cell Biology

Background:

• Protein databases integrate diverse data, including curated and primary sources.
• Swiss-Prot uses predictions and literature for subcellular location, while Human Protein Atlas (HPA) uses expert-annotated microscopy images.
• Reconciling these diverse protein location data sources presents a significant challenge.

Purpose of the Study:

• To quantitatively evaluate the consistency of subcellular location annotations between HPA and Swiss-Prot.
• To analyze the variation of protein subcellular locations across different cell lines and tissues.
• To propose methods for deriving and integrating protein subcellular location data.

Main Methods:

• Quantitative comparison of subcellular location annotations between Swiss-Prot and HPA.
• Analysis of protein location variations across cell lines and tissues.
• Evaluation of annotation consistency at multiple hierarchical levels.

Main Results:

• Significant discrepancies were observed between HPA and Swiss-Prot subcellular location annotations.
• Protein locations exhibit considerable variation across different cell lines and tissues.
• Proteins with highly variable subcellular locations are more frequently associated with disease biomarkers.

Conclusions:

• Current protein subcellular location annotations in major databases show significant inconsistencies.
• Integrating and deriving protein location data requires robust procedures to address these differences.
• Subcellular location analysis holds potential for identifying and screening protein biomarkers, especially for variable proteins.