A, The Alzheimer’s disease (AD) global signaling network. two modules of receptors and transcription factors are readily apparent and labeled based on enrichment of transcription factors by cluster. B, Heatmaps of transcription factor activation score for AD-specific transcription factors (left) and correlation of transcription factor activation score with receptor expression (right). Transcription factors are binned according to their membership to the astrocyte or oligodendrocyte modules from the AD global signaling network. Cells are ordered and colored according to their cluster. Receptors found only in AD are marked with arrows. Connections between receptor and transcription factors are marked with an ‘x’ on the correlation heatmap. C, Example feature plots of gene expression and activation scores for specific receptor-transcription factor pairs identified by domino in the AD condition. D, The healthy global signaling network. Two modules of receptors and transcription factors are readily apparent and labeled based on enrichment of transcription factors by cluster. E, Heatmaps of transcription factor activation score for healthy-specific transcription factors (left) and correlation of transcription factor activation score with receptor expression (right). Transcription factors are binned according to their membership to the astrocyte or oligodendrocyte modules from the global signaling network. Cells are ordered and colored according to their cluster. Receptors found only in the healthy signaling network are marked with arrows. Connections between receptor and transcription factors are marked with an ‘x’ on the correlation heatmap. F, Example feature plots of gene expression and activation scores for specific receptor-transcription factor pairs identified by domino in healthy cells.