Journal article
A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases
PLoS biology, Vol.21(4), e3002058
04/20/2023
DOI: 10.1371/journal.pbio.3002058
PMCID: PMC10118126
PMID: 37079537
Abstract
Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes. Analysis of 40 common human brain diseases identifies 5 major transcriptional patterns, representing tumor-related, neurodegenerative, psychiatric and substance abuse, and 2 mixed groups of diseases affecting basal ganglia and hypothalamus. Further, for diseases with enriched expression in cortex, single-nucleus data in the middle temporal gyrus (MTG) exhibits a cell type expression gradient separating neurodegenerative, psychiatric, and substance abuse diseases, with unique excitatory cell type expression differentiating psychiatric diseases. Through mapping of homologous cell types between mouse and human, most disease risk genes are found to act in common cell types, while having species-specific expression in those types and preserving similar phenotypic classification within species. These results describe structural and cellular transcriptomic relationships of disease risk genes in the adult brain and provide a molecular-based strategy for classifying and comparing diseases, potentially identifying novel disease relationships.
Details
- Title: Subtitle
- A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases
- Creators
- Yashar G. Zeighami - Douglas Mental Health University InstituteTrygve E. A. Bakken - Allen InstituteThomas Nickl-Jockschat - University of Iowa, Iowa Neuroscience InstituteZeru Peterson - University of Iowa, PsychiatryAnil G. S. Jegga - Cincinnati Children's Hospital Medical CenterJeremy A. Miller - Allen InstituteJay Schulkin - University of WashingtonAlan C. Evans - McGill Univ, Montreal Neurol Inst, Montreal, PQ, CanadaEd S. Lein - Allen InstituteMichael Hawrylycz - Allen Institute
- Resource Type
- Journal article
- Publication Details
- PLoS biology, Vol.21(4), e3002058
- DOI
- 10.1371/journal.pbio.3002058
- PMID
- 37079537
- PMCID
- PMC10118126
- NLM abbreviation
- PLoS Biol
- ISSN
- 1544-9173
- eISSN
- 1545-7885
- Publisher
- PLOS
- Number of pages
- 29
- Grant note
- Canada First Research Excellence Fund Healthy Lives (HBHL) initiative New Recruit Start-Up Supplements Program Reeau de Bio-Imagerie du Quebec (RBIQ/QBIN) R01MH123220; 08/01/2020-07/31/2022 / A Community Framework for Data-driven Brain Transcriptomic Cell Type Definition, Ontology, and Nomenclature grant
- Language
- English
- Date published
- 04/20/2023
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984473217702771
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