For the brown and the tan modules, the GO and top pathways annotation were mostly related to synaptic functions, ion channels, and ligand-receptor interactions (Tables S5, S6), which is in harmony with their more significant eigengene upregulation in probands at the later time point (Figure 2A). The brown module displayed the strongest enrichment with respect to the SFARI autism gene dataset, a collection of genetic information that includes data from linkage and association studies, cytogenetic abnormalities, and specific mutations associated with ASD (https://gene.sfari.org) (SFARI category S to 4)(Abrahams et al., 2013) (p-value = 6.51E-5). Among the top 100 hub genes of the brown module, 64 were upregulated at TD31, including molecules involved in synaptic assembly, ion transport, and post-synaptic signaling (i.e., NRXN1, NRXN2, SLITRK1, CAMK2B, CAMK1D, NRSN1, SYT13, GRIN1, SCN2A) (Table S7). Among the hub genes, NRXN1, SCN2A, and TSPAN7 were both significantly upregulated and overlapping with genes in the SFARI autism database (Figure 2C). The tan module was characterized by an upregulation at TD31 of transcripts for several potassium channels and for key components of GABAergic neurons, including the
