@article{e1e0fc802a864680990273d062ac593a,
title = "An anatomically comprehensive atlas of the adult human brain transcriptome",
abstract = "Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topographythe closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.",
author = "Hawrylycz, {Michael J.} and Lein, {Ed S.} and Guillozet-Bongaarts, {Angela L.} and Shen, {Elaine H.} and Lydia Ng and Miller, {Jeremy A.} and {Van De Lagemaat}, {Louie N.} and Smith, {Kimberly A.} and Amanda Ebbert and Riley, {Zackery L.} and Chris Abajian and Beckmann, {Christian F.} and Amy Bernard and Darren Bertagnolli and Boe, {Andrew F.} and Cartagena, {Preston M.} and {Mallar Chakravarty}, M. and Mike Chapin and Jimmy Chong and Dalley, {Rachel A.} and Daly, {Barry David} and Chinh Dang and Suvro Datta and Nick Dee and Dolbeare, {Tim A.} and Vance Faber and David Feng and Fowler, {David R.} and Jeff Goldy and Gregor, {Benjamin W.} and Zeb Haradon and Haynor, {David R.} and Hohmann, {John G.} and Steve Horvath and Howard, {Robert E.} and Andreas Jeromin and Jochim, {Jayson M.} and Marty Kinnunen and Christopher Lau and Lazarz, {Evan T.} and Changkyu Lee and Lemon, {Tracy A.} and Ling Li and Yang Li and Morris, {John A.} and Overly, {Caroline C.} and Parker, {Patrick D.} and Parry, {Sheana E.} and Melissa Reding and Royall, {Joshua J.} and Jay Schulkin and Sequeira, {Pedro Adolfo} and Slaughterbeck, {Clifford R.} and Smith, {Simon C.} and Sodt, {Andy J.} and Sunkin, {Susan M.} and Swanson, {Beryl E.} and Vawter, {Marquis P.} and Derric Williams and Paul Wohnoutka and {Ronald Zielke}, H. and Geschwind, {Daniel H.} and Hof, {Patrick R.} and Smith, {Stephen M.} and Christof Koch and Grant, {Seth G.N.} and Jones, {Allan R.}",
note = "Funding Information: Acknowledgements We wish to thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement, and support. We express our gratitude to past and present Allen Institute staff members R. Adams, K. Aiona, A. Alpisa, J. Arnold, C. Bennet, K. Brouner, S. Butler, E. Byrnes, S. Caldejon, J. Campiche, A. Carey, J. Chen, C. Copeland, C. Cuhaciyan, T. Desta, N. Dotson, S. Faber, T. Fliss, E. Fulfs, G. Gee, T. Gilbert, L. Gourley, G. Gu, J. Heilman, N. Ivanov, K. Keyser, A. Kriedberg, J. Laoenkue, F. Lee, S. Levine, L. Luong, N. Mastan, N. Mosqueda, E. Mott, N. Motz, D. Muzia, K. Ngo, A. Oldre, E. Olson, J. Parente, J. Phillips, L. Potekhina, T. Roberts, K. Roll, D. Rosen, M. Sarreal, S. Shapouri, N. Shapovalova, C. Simpson, D. Simpson, M. Smith, N. Stewart, K. Sweeney, A. Szafer, L. Velasquez, U. Wagley, W. Wakeman, C. White and B. Youngstrom for their technical assistance. We thank C. Long for mechanical engineering contract work. We thank R. Gullapalli, A. McMillan and R. Morales for post-mortem magnetic resonance imaging and radiology interpretation of MR data; J. Cottrell, M. Davis, R. Johnson, K. Moraniec, R. Vigorito, A. Weldon and the NICHD Brain and Tissue Bank for Developmental Disorders for tissue acquisition and processing; J. Davis for donor coordination; F. Mamdani, M. Martin, E. Moon, L. Morgan, B. Rollins and D. Walsh for tissue processing and psychological autopsy (DW); D. Patel for magnetic resonance imaging; and J. Sonnen for consultation on tissue microneuropathology. We also thank the External RNA Controls Consortium (ERCC), the US National Institute of Standards (NIST) and Technology, and M. Salitfor access to ERCCtranscriptsduringPhase V testing.Weare gratefultoBeckmanCoulterGenomics (formerly Cogenics) and their staff P. Hurban, E. Lobenhofer, K. Phillips, A. Rouse and S. Beaver for microarray data generation and design of the custom Agilent array. We also wish to thank the Allen Human Brain Atlas Advisory Council members D. Geschwind, R. Gibbs, P. Hof, E. Jones, C. Koch, C. Saper, L. Swanson, A. Toga and D. Van Essen for their scientific guidance and dedication to the successful execution of this project. The project described was supported in part by Grant Numbers 1C76HF15069-01-00 and 1 1C76HF19619-01-00 from the Department of Health and Human Services Health Resources and Services Administration Awards and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Department of Health and Human Services Health Resources and Services Administration Awards. S.G.N.G and L.V.L. were supported by the MRCD, Wellcome Trust and European Union Seventh Framework Programme under grants 241498 EUROSPIN, 242167 SynSys, and 241995 GENCODYS Projects.",
year = "2012",
month = sep,
day = "20",
doi = "10.1038/nature11405",
language = "English",
volume = "489",
pages = "391--399",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7416",
}