There are 45 out of 104 HuGE HhAntag691 depression genes not in our DEPgenes, with calculated mean combined score of 6.6 below our cutoff of 15. Some well-known depression candidate genes that do not have scores greater than 0.01 in the HuGE genes are included in our DEPgenes, such as DBH, CHRNA7, and GABRA3, which were all ranked in the top list of DEPgenes. Without proper evaluation of weighting scheme, using other search engines may result in omitting important information for follow-up studies. The list of the prioritized MG132 DEPgenes can be used for individual replication and to further explore the biological roles of them in depression using basic science approaches. The top seven DEPgenes are DBH, BDNF, SLC6A4, NGFR, TNF, GSK3B, and CHRNA7. The roles of these high-ranking DEPgenes in depression were supported by review articles and empirical studies. For instance, increased dopaminergic activity may play a primary role in depression. Dopamine beta -hydroxylase catalyses the key step in biosynthesis of the neurotransmitter noradrenaline from dopamine, and low DBH activity from a variety of brain regions is a possible risk factor for developing depression. Serotonin transporter and serotonin receptor genes are among the strongest candidates underlying the etiology of depression. A commonly prescribed medication for treating depression is selective serotonin reuptake inhibitors , which acts to keep the balance in the serotonin neurotransmitter system in the brain. Brain-derived neurotrophic factor is a neuroprotective protein which alters the balance of neurotoxic and neuroprotective responses to stress by preventing hippocampal cells from damage and is suggested to be associated with depression. The nerve growth factor receptor encodes the affinity and modulates the activity of tyrosine kinases for neurotrophin family, and plays a potential role in ligand binding and signaling. The NGFR was reported to have protective effect against the development of depressive disorder. The tumor necrosis factor plays roles in altering neural-immune interactions, including levels of proinflammatory cytokines, increased pain sensitivity and elevated inflammatory activity. Prior evidence supports that the development of depression is related to the levels of proinflammatory cytokines TNF-a and to interleukin-6 in the brain. Glycogen synthase kinase 3 beta is an enzyme involved in energy metabolism and neuronal cell development, which are processes related to depression. The GSK3B plays an important role in the action of mood stabilizer. Lastly, the a7 neuronal nicotinic acetylcholine receptor subunit gene is a cholinergic receptor, which has been reported to be associated with a sensory deficit in common mental illness and neurochemical changes in depression-like behavior.