Next, we identified several key regulatory transcription factors in each cell type using the expression and accessibility of all target genes within the trans-regulatory network constructed by LINGER43 (Extended Data Fig. 8). For example, in D2 medium spiny neurons, the transcription factor predicted to have the most significant altered activity in AUD, based on the chromatin openness of its target genes, was FOXO1 (Forkhead transcriptional factor O1, Extended Data Fig. 8), which has been previously shown to regulate energy homeostasis in neurons49 and was linked to depression in multiple recent studies.50,51
