Fold Enrichment

Published

Also known as: fold-enrichment ratio, tissue enrichment ratio

The ratio of a protein's expression in a target tissue vs. its highest expression in any other tissue. 4x means 4 times more abundant in the target tissue than anywhere else.

Source: Human Protein Atlas (proteinatlas.org)

Fold enrichment is a direct, interpretable measure of tissue preferential expression. Unlike the tau score (which is a population-level metric across all tissues), fold enrichment compares the target tissue against the single highest-expressing alternative.

Formula

Fold Enrichment = tissue_nTPM / max_other_nTPM

Example — AHSG in liver:
  Liver nTPM:  5,638.7
  Next highest (kidney): 1.3 nTPM
  Fold enrichment: 5,638.7 / 1.3 = 4,337x

Interpretation

Fold EnrichmentInterpretation
≥ 4xConsidered tissue-preferential (HPA standard)
≥ 10xStrong tissue specificity
≥ 100xHighly tissue-restricted
≥ 1000xNear-exclusive expression

Relationship to Tau Score

Fold enrichment and tau score are complementary:

  • Tau summarizes specificity across all tissues at once
  • Fold enrichment quantifies the contrast against the best alternative tissue

A protein can have a moderate tau but very high fold enrichment (if it is moderately expressed in two tissues but 1000x higher in one), or high tau but moderate fold enrichment (if it is expressed at low levels in many tissues with one dominant).

Both metrics together provide a more complete picture than either alone.