PICKLE

PICKLE reconstructs and integrates protein-protein interaction (PPI) networks for human and mouse by mapping heterogeneous PPI datasets onto a genetic information ontology to enable comparative and systems-level interactome analyses.

Key Features:

• Integration of Multiple Datasets: Integrates heterogeneous primary PPI datasets without prior transformations, preserving original dataset characteristics and enabling cross-checking across source databases to identify potential false positives.
• Reference Proteome Utilization: Uses the UniProtKB/Swiss-Prot manually reviewed complete proteomes of humans (RHCP) and mice as the foundational protein-node sets, covering approximately 60% of the human proteome and yielding a scale-free network structure.
• Genetic Information Ontology: Superimposes PPI datasets onto an ontology network that connects genes, nucleotide sequences (mRNAs), and proteins (UniProt entries), respecting genetic information flow without irreversible normalization.
• Reversible Normalization: Allows reversible normalization of interactions to any level of genetic reference (protein or gene) while preserving links to original dataset mappings.
• Cross-Species Interactome Comparison: Extends to the mouse interactome (PICKLE 3.0) and incorporates orthologous relationships with human PPI data to facilitate comparative analysis and detect inconsistencies.

Scientific Applications:

• Systems Biology: Provides structured and comprehensive human and mouse interactomes for network topology analysis and systems-level investigations.
• Biomedical Research: Supports identification of highly connected (essential) proteins and their correlation with critical biological roles relevant to disease mechanism studies.
• Functional Experiment Design: Highlights unrepresented proteins potentially involved in specialized physiological conditions and directs targeted text-mining of relevant PPI data.

Methodology:

Integrates heterogeneous primary PPI datasets without prior transformations; maps datasets onto an ontology connecting genes, mRNAs, and UniProt protein entries; enables reversible normalization to gene or protein reference levels; performs cross-checking across source databases; and incorporates orthologous relationships for mouse–human comparisons.