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Building a negative-control signature library

Common stress, cell-cycle, interferon, and dissociation programs belong in every enrichment workflow.

Why controls belong early

Single-cell enrichment is vulnerable to programs that recur across many tissues and conditions. Stress, cell cycle, interferon response, and dissociation effects can produce convincing but nonspecific signal.

Build a reference set

Maintain versioned signatures for common technical and biological programs. Test the target gene set against these controls using the same scoring and resampling procedure.

Interpret overlap

Overlap does not automatically invalidate a result. It changes the claim. A disease program may include a common response, but the specific component must be identified.

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