Why rescue-based transcript ranking can mislead: normalization displacement and shared-control coupling in perturbation transcriptomics
When a disease-associated transcript moves toward control after a phenotypically effective rescue, the pattern can be read as mediator evidence. We show why this inference can fail even when the computation is reproducible. Across normalization schemes in PLP1-mutant Jimpy brain (GSE277705), the original negative-interaction criterion classified 47.6-76.0% of all expressed genes and 77.6-86.6% of…
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