Transcriptional cartography integrates multiscale biology of the human cortex
The cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/86933 |
| _version_ | 1827356070041878528 |
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| author | Konrad Wagstyl Sophie Adler Jakob Seidlitz Simon Vandekar Travis T Mallard Richard Dear Alex R DeCasien Theodore D Satterthwaite Siyuan Liu Petra E Vértes Russell T Shinohara Aaron Alexander-Bloch Daniel H Geschwind Armin Raznahan |
| author_facet | Konrad Wagstyl Sophie Adler Jakob Seidlitz Simon Vandekar Travis T Mallard Richard Dear Alex R DeCasien Theodore D Satterthwaite Siyuan Liu Petra E Vértes Russell T Shinohara Aaron Alexander-Bloch Daniel H Geschwind Armin Raznahan |
| author_sort | Konrad Wagstyl |
| collection | DOAJ |
| description | The cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate, and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization – ranging from protein–protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources, and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research. |
| first_indexed | 2024-03-08T04:54:28Z |
| format | Article |
| id | doaj.art-53c392b8d0c449c5b682ca99e6adbe03 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T04:54:28Z |
| publishDate | 2024-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-53c392b8d0c449c5b682ca99e6adbe032024-02-07T17:10:45ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011210.7554/eLife.86933Transcriptional cartography integrates multiscale biology of the human cortexKonrad Wagstyl0https://orcid.org/0000-0003-3439-5808Sophie Adler1Jakob Seidlitz2Simon Vandekar3Travis T Mallard4Richard Dear5Alex R DeCasien6Theodore D Satterthwaite7https://orcid.org/0000-0001-7072-9399Siyuan Liu8https://orcid.org/0000-0003-3661-6248Petra E Vértes9https://orcid.org/0000-0002-0992-3210Russell T Shinohara10Aaron Alexander-Bloch11Daniel H Geschwind12https://orcid.org/0000-0003-2896-3450Armin Raznahan13https://orcid.org/0000-0002-5622-1190Wellcome Centre for Human Neuroimaging, University College London, London, United KingdomUCL Great Ormond Street Institute for Child Health, Holborn, United KingdomDepartment of Psychiatry, University of Pennsylvania, Philadelphia, United States; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, United StatesDepartment of Biostatistics, Vanderbilt University, Nashville, United StatesPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, United States; Department of Psychiatry, Harvard Medical School, Boston, United StatesDepartment of Psychiatry, University of Cambridge, Cambridge, United KingdomSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesDepartment of Psychiatry, University of Pennsylvania, Philadelphia, United States; Lifespan Informatics and Neuroimaging Center, University of Pennsylvania School of Medicine, Philadelphia, United StatesSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesDepartment of Psychiatry, University of Cambridge, Cambridge, United KingdomPenn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Psychiatry, University of Pennsylvania, Philadelphia, United States; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, United StatesCenter for Autism Research and Treatment, Semel Institute, Program in Neurogenetics, Department of Neurology and Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesThe cerebral cortex underlies many of our unique strengths and vulnerabilities, but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate, and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization – ranging from protein–protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources, and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research.https://elifesciences.org/articles/86933cortextranscriptomicsneuroimagingmultiscale |
| spellingShingle | Konrad Wagstyl Sophie Adler Jakob Seidlitz Simon Vandekar Travis T Mallard Richard Dear Alex R DeCasien Theodore D Satterthwaite Siyuan Liu Petra E Vértes Russell T Shinohara Aaron Alexander-Bloch Daniel H Geschwind Armin Raznahan Transcriptional cartography integrates multiscale biology of the human cortex eLife cortex transcriptomics neuroimaging multiscale |
| title | Transcriptional cartography integrates multiscale biology of the human cortex |
| title_full | Transcriptional cartography integrates multiscale biology of the human cortex |
| title_fullStr | Transcriptional cartography integrates multiscale biology of the human cortex |
| title_full_unstemmed | Transcriptional cartography integrates multiscale biology of the human cortex |
| title_short | Transcriptional cartography integrates multiscale biology of the human cortex |
| title_sort | transcriptional cartography integrates multiscale biology of the human cortex |
| topic | cortex transcriptomics neuroimaging multiscale |
| url | https://elifesciences.org/articles/86933 |
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