Functional genomics of the brain: Uncovering networks in the CNS using a systems approach

The central nervous system (CNS) is undoubtedly the most complex human organ system in terms of its diverse functions, cellular composition, and connections. Attempts to capture this diversity experimentally were the foundation on which the field of neurobiology was built. Until now though, techniques were either painstakingly slow or insufficient in capturing this heterogeneity. In addition, the combination of multiple layers of information needed for a complete picture of neuronal diversity from the epigenome to the proteome requires an even more complex compilation of data. In this era of high-throughput genomics though, the ability to isolate and profile neurons and brain tissue has increased tremendously and now requires less effort. Both microarrays and next-generation sequencing have identified neuronal transcriptomes and signaling networks involved in normal brain development, as well as in disease. However, the expertise needed to organize and prioritize the resultant data remains substantial. A combination of supervised organization and unsupervised analyses are needed to fully appreciate the underlying structure in these datasets. When utilized effectively, these analyses have yielded striking insights into a number of fundamental questions in neuroscience on topics ranging from the evolution of the human brain to neuropsychiatric and neurodegenerative disorders. Future studies will incorporate these analyses with behavioral and physiological data from patients to more efficiently move toward personalized therapeutics.