Fig. 6: Co-regulatory networks of protein dynamics in gastruloids link to shared phenotypes and developmental disorders.

a, Overlap of proteins detected across our dataset, GenCC and DDD. The heatmaps correspond to the temporal abundance changes of human proteins (rows) associated with a specific developmental disorder across human gastruloid development (columns). b, Distribution of mean Pearson correlation coefficients across GenCC disease sets. Only diseases with ≥2 genes are plotted. Mean r_Pearson was calculated by averaging Pearson correlation coefficients for detected pairs of proteins in our dataset. c, Histogram of the number of developmental disorders associated (y axis) with genes comprising protein complexes (x axis). Complexes were associated with an average of 2.95 ± 2.68 developmental diseases. d, Co-regulation network of Commander complex subunits. Size of orange nodes indicates the significance of cooperative association (−log₁₀ of the adjusted P value; Fisher’s exact test; Methods). Proteins associated with developmental disorders (blue stars) were linked to the Commander complex co-regulation network. e, Heatmap depicting the extent of shared phenotypic overlap (columns) across genes (rows) in the Commander subnetwork. f, Representative images of WT (wild-type), COMMD10 KO, COMMD9 KO, DPYSL4 KO and PRKACB KO gastruloids. n = 48 gastruloids per genotype. Scale bars, 200 μm. g, Boxplots comparing the area and major axis length of wild-type versus genetically perturbed gastruloids. Significance was determined using a two-sided standard t-test (n ≥ 8 for each genetic knockout). Boxplots show the median (centre line), 25th–75th percentiles (box) and 1.5× the interquartile range (line; end points signify maxima and minima).