Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments

Courtney R. Sullivan; Catharine A. Mielnik; Sinead M. O’Donovan; Adam J. Funk; Eduard Bentea; Erica A.K. DePasquale; Zhexing Wen; Vahram Haroutunian; Pavel Katsel; Amy J. Ramsey; Jarek Meller; Robert E. McCullumsmith

We next probed for kinases that when knocked down in various cell lines, have upregulated genes similar to the panels of clustered upregulated genes from our iLINCS clustering analysis. Top hits included several serine/threonine-protein kinases (AKT1, MAP2K2, PTK2, ATR) as well as G-protein coupled receptors (GPCRs) involved in energy homeostasis (NMUR2, FFAR1) ( Figure S8 ). We next probed for transcription factors that had occupancy sites for our panels of clustered upregulated genes. We found several transcription factors that play important roles in developmental processes, such as WT1, TRIM28, NFIB, NUCKS1, and TCF3 ( Figure S9 ). Finally, our database of genotypes and phenotypes (dbGaP) analysis implicates diabetes as the most relevant phenotype ( Figure S10 ). A summary of these findings can be found in Table 3 .