APP and Alzheimer disease: The set of genes differentially expressed in the cells with a Myrf deletion compared with the control was significantly enriched in the 5-layer downstream neighborhood of MYRF in the COLBN (FE = 2.5, p = 7.5e-33; Fig. 5a, Fig. 6a-b), thus validating the topology of the subnetwork regulated by MYRF. The validated downstream targets of MYRF include PLD1, which encodes a protein that regulates the shuttling of APP and is associated with APP in AD brains [46, 47], as well as APLP1, which encodes a protein that has been shown to accumulate within neuritic plaques [48].