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 downregulated genes similar to our panels of clustered downregulated genes from our iLINCS clustering analysis. Top hits included several kinases involved in fatty acid metabolism and energy homeostasis (RXRA, PPARG, PXK), cellular growth (RYK, WEE1, ABL2), GPCRs (GPR37, LPHN1), and a glucocorticoid receptor (NR3C1) ( Figure S15 ). We next probed for transcription factors that had occupancy sites for our panels of clustered downregulated genes. We found several transcription factors that play important roles in cell proliferation (MYCN, MYC, E2F1, E2F4, FOXM1), development (NUCKS1, POU5F1) , and erythroid function (EKLF) ( Figure S16 ). Finally, our dbGaP analysis implicates carcinoma, memory, and Grave's Disease as the most relevant phenotypes ( Figure S17 ). A summary of these findings can be found in Table 3 .