NPA

NPA computes Network Perturbation Amplitude scores from gene expression fold-changes by mapping them onto nodes in two-layer biological network models to quantify perturbation of predefined mechanisms.

Key Features:

• R package implementation: Provides the NPA functionality as an R package.
• Two-layer network models: Uses two-layer networks to represent mechanistic relationships between molecular entities and biological processes.
• Node differential computation: Translates gene expression fold-changes into differential values for individual network nodes.
• Network Perturbation Amplitude (NPA) scoring: Summarizes node-level changes at the network level to produce quantitative NPA scores.
• Leading node analysis: Identifies key nodes that drive network-level changes.
• Biological Impact Factor (BIF): Aggregates individual NPA scores across multiple networks to compute an overall BIF reflecting cumulative biological impact.
• Precompiled network data packages: Includes eight two-layer networks representing processes such as xenobiotic metabolism, apoptosis, and epithelial immune innate activation.
• Published algorithm implementation: Implements a previously published algorithm for computing NPAs.

Scientific Applications:

• Systems toxicology: Quantifies perturbation of key mechanisms to assess compounds or treatments for potential toxicity.
• Mechanistic interpretation of gene expression: Maps transcriptome fold-changes to network models to interpret effects on biological processes.
• Cumulative impact assessment: Uses aggregated NPA scores (BIF) to quantify overall biological impact of perturbing agents.
• Cross-study and model analysis: Applies to gene expression datasets, including those from animal models, to compare network-level responses.

Methodology:

Translates gene expression fold-changes into node differential values within two-layer networks; summarizes node differentials to compute Network Perturbation Amplitude (NPA); performs leading node analysis to identify drivers of network changes; aggregates NPAs across networks to calculate the Biological Impact Factor (BIF); implements a previously published NPA algorithm.