Abstract
Neuroscience research has entered a phase of key discoveries in the realm of neurogenomics owing to strong financial and intellectual support for resource building and tool development. The previous challenge of tissue heterogeneity has been met with the application of techniques that can profile individual cells at scale. Moreover, the ability to perturb genes, gene regulatory elements and neuronal activity in a cell-type-specific manner has been integrated with gene expression studies to uncover the functional underpinnings of the genome at a systems level. Although these insights have necessarily been grounded in model systems, we now have the opportunity to apply these approaches in humans and in human tissue, thanks to advances in human genetics, brain imaging and tissue collection. We acknowledge that there will probably always be limits to the extent to which we can apply the genomic tools developed in model systems to human neuroscience; however, as we describe in this Perspective, the neuroscience field is now primed with an optimal foundation for tackling this ambitious challenge. The application of systems-level network analyses to these datasets will facilitate a deeper appreciation of human neurogenomics that cannot otherwise be achieved from directly observable phenomena.
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Acknowledgements
The authors thank members of the Bhaduri and Konopka laboratories for feedback on the manuscript and R. Vollmer for assistance with Figs. 1 and 2. The Bhaduri laboratory is supported by NIMH (UM1MH130991, R00NS111731), Klingenstein-Simons Neuroscience Fellowship, Brain Behavior & Research Young Investigator Award, and The Alfred P. Sloan Foundation Fellowship. G.K. is a Jon Heighten Scholar in Autism Research and Townsend Distinguished Chair in Research on Autism Spectrum Disorders at UT Southwestern. The Konopka laboratory is supported by NIMH (MH126481), NINDS (NS126143, NS115821), NHGRI (HG011641), the Simons Foundation (947591), and the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition—Scholar Award (220020467).
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Konopka, G., Bhaduri, A. Functional genomics and systems biology in human neuroscience. Nature 623, 274–282 (2023). https://doi.org/10.1038/s41586-023-06686-1
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DOI: https://doi.org/10.1038/s41586-023-06686-1
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