Pathway Enrichment

Once protein-level sensitivity is computed, the system aggregates responses at the pathway or module level.

Two complementary approaches

1. Effect size aggregation

For each pathway:

• Mean NSS
• Median NSS
• Upper quantile (top responders)
• Number of proteins

This captures how strongly a pathway responds overall.

2. Statistical enrichment

Two statistical frameworks are used:

• Fisher’s exact test for binary hit sets
• Mann–Whitney U test for continuous scores

Both are corrected using Benjamini–Hochberg FDR.

Why both methods

• Binary enrichment identifies strong responders
• Continuous enrichment detects subtle but consistent shifts

Using both provides a more complete view.

Interpretation

• Enriched pathways indicate coordinated NADPH sensitivity
• High NSS pathways often correspond to:
  • redox systems
  • metabolic hubs
  • cofactor-dependent enzymes

This step moves analysis from individual proteins to biological systems.