Finally, upstream regulators in our dataset showed similar predicted z-scores to those seen in colonic biopsies from colitis patients (Zhao et al., 2015; Fig. 7), validating that these S839I mice can indeed serve as a preclinical model to study gut inflammation in humans mediated by hyperactive GUCY2C mutations (Crowley et al., 2020). Here, GUCY2C is linked to colitis.