Recalibrating differential gene expression by genetic dosage variance prioritizes functionally relevant genes

Fold change recalibration using V^G. (A) Depending on variability of a gene, an observed fold change may be within the natural variation that is observed in the general population. V^G is an estimate of this population variance. (B) Correlation of V^G_H with other gene metrics. Negative correlations are colored dark gray; positive correlations are light gray. (C) Distribution of functional categories in genes split by V^G_H decile. Some functional categories like transcription- and translation-associated genes were enriched for small V^G_H estimates, and others, like receptors, were enriched for high V^G_H estimates. (D) Correlation of gene metrics with experimental gene expression variance. Data sourced from Alasoo et al. (2018) studying the effects of IFNG treatment on 81 human macrophage samples. (E) Correlation of gene metrics with absolute gene expression changes in the IFNG experiment. (F) Concept of gene expression recalibration using V^G. As a result of this process, genes are prioritized not by nominal log fold change (FC) but by recalibrated log fold change ().