PROTEO: Peptide evidence for the human genome

PROTEO interrogates peptide evidence from human proteomics datasets to determine whether a single dominant protein isoform is expressed per protein-coding gene across tissues and cell types.

Key Features:

• Large-scale data integration: Analyzes peptides from eight large-scale human proteomics experiments and databases to capture protein expression across tissues and cell types.
• Peptide evidence filtering: Considers only peptides observed in at least two independent experiments to increase robustness.
• Isoform dominance analysis: Identifies whether a single dominant splice isoform is observed at the protein level for each gene irrespective of tissue or cellular context.
• Cross-validation with orthogonal references: Cross-references findings with consensus coding sequence variants curated by genome curation teams and APPRIS principal isoforms, which are predicted based on conservation of protein sequence, structure, and function.
• Comparison with transcriptomics: Assesses concordance between protein-level dominant isoforms and recent RNAseq study findings.

Scientific Applications:

• Resolving transcript-protein discrepancies: Clarifies contradictions from previous large-scale transcript expression studies by providing protein-level evidence.
• Alternative splicing research: Supplies proteomic evidence to identify dominant isoforms for studies of alternative splicing and its functional consequences.
• Genome annotation and curation: Supports annotation decisions by comparing proteomic isoform dominance with consensus coding sequence variants and APPRIS principal isoforms.

Methodology:

Interrogates peptides from eight large-scale human proteomics experiments and databases, requires peptides to be present in at least two experiments, identifies a dominant protein isoform per gene, and cross-references results with consensus coding sequence variants curated by genome curation teams and APPRIS principal isoforms.