Interactions between genes based on co-expression relationships were established by forming a gene network, and these connections are represented by a HIVE plot, as a traditional gene network, and a compressed hub gene network (Fig. 1G-I) (Krzywinski et al., 2012). With highly connected intramodular hub genes centrally located in the module, the connections to the outer rim allow for further elucidating the biological meaning of EtOH related modules. For example, we have identified two top hub genes, SCUBE3 and SLC22A5 (presented as red dots in Fig. 1G-I), in a representation of genes downregulated in H9 cells upon EtOH treatment and differentiation. The SLC22A5 gene functions in the transport of carnitine into the cell. More specifically, SLC22A5 facilitates the function of protein OCTN2, which is embedded in the cell membrane and acts as a transporter for carnitine (Tamai et al., 1998). Carnitine plays an essential role in transporting fatty acid from cytosol into the mitochondrial matrix to be broken down into usable metabolic energy. The SLC22A5 gene is therefore an important regulator of fatty acid metabolism, and is necessary for the
