A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases.
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...
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Public Library of Science (PLoS)
2023-04-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002058&type=printable |
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| author | Yashar Zeighami Trygve E Bakken Thomas Nickl-Jockschat Zeru Peterson Anil G Jegga Jeremy A Miller Jay Schulkin Alan C Evans Ed S Lein Michael Hawrylycz |
| author_facet | Yashar Zeighami Trygve E Bakken Thomas Nickl-Jockschat Zeru Peterson Anil G Jegga Jeremy A Miller Jay Schulkin Alan C Evans Ed S Lein Michael Hawrylycz |
| author_sort | Yashar Zeighami |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e3161a5782d644bfb0511f353e3e4f28 |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-e3161a5782d644bfb0511f353e3e4f282025-08-20T02:57:17ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-04-01214e300205810.1371/journal.pbio.3002058A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases.Yashar ZeighamiTrygve E BakkenThomas Nickl-JockschatZeru PetersonAnil G JeggaJeremy A MillerJay SchulkinAlan C EvansEd S LeinMichael HawrylyczGenes 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002058&type=printable |
| spellingShingle | Yashar Zeighami Trygve E Bakken Thomas Nickl-Jockschat Zeru Peterson Anil G Jegga Jeremy A Miller Jay Schulkin Alan C Evans Ed S Lein Michael Hawrylycz A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. PLoS Biology |
| title | A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. |
| title_full | A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. |
| title_fullStr | A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. |
| title_full_unstemmed | A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. |
| title_short | A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases. |
| title_sort | comparison of anatomic and cellular transcriptome structures across 40 human brain diseases |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002058&type=printable |
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