Brain Cell Type Specific Gene Expression and Co-expression Network Architectures
Abstract Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA express...
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Nature Portfolio
2018
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oai:doaj.org-article:4f166a71fd834b69ad514d8d5441276a2021-12-02T15:08:55ZBrain Cell Type Specific Gene Expression and Co-expression Network Architectures10.1038/s41598-018-27293-52045-2322https://doaj.org/article/4f166a71fd834b69ad514d8d5441276a2018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27293-5https://doaj.org/toc/2045-2322Abstract Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell “signatures,” which were well conserved across data sets. We validated that the relative expression of top cell type markers are associated with proxies for cell type proportions in bulk RNA expression data from postmortem human brain samples. We further validated novel marker genes using an orthogonal ATAC-seq dataset. We performed multiscale coexpression network analysis of the single cell data sets and identified robust cell-specific gene modules. To facilitate the use of the cell type-specific genes for cell type proportion estimation and deconvolution from bulk brain gene expression data, we developed an R package, BRETIGEA. In summary, we identified a set of novel brain cell consensus signatures and robust networks from the integration of multiple datasets and therefore transcend limitations related to technical issues characteristic of each individual study.Andrew T. McKenzieMinghui WangMads E. HaubergJohn F. FullardAlexey KozlenkovAlexandra KeenanYasmin L. HurdStella DrachevaPatrizia CasacciaPanos RoussosBin ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-19 (2018) |
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Medicine R Science Q Andrew T. McKenzie Minghui Wang Mads E. Hauberg John F. Fullard Alexey Kozlenkov Alexandra Keenan Yasmin L. Hurd Stella Dracheva Patrizia Casaccia Panos Roussos Bin Zhang Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
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Abstract Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell “signatures,” which were well conserved across data sets. We validated that the relative expression of top cell type markers are associated with proxies for cell type proportions in bulk RNA expression data from postmortem human brain samples. We further validated novel marker genes using an orthogonal ATAC-seq dataset. We performed multiscale coexpression network analysis of the single cell data sets and identified robust cell-specific gene modules. To facilitate the use of the cell type-specific genes for cell type proportion estimation and deconvolution from bulk brain gene expression data, we developed an R package, BRETIGEA. In summary, we identified a set of novel brain cell consensus signatures and robust networks from the integration of multiple datasets and therefore transcend limitations related to technical issues characteristic of each individual study. |
format |
article |
author |
Andrew T. McKenzie Minghui Wang Mads E. Hauberg John F. Fullard Alexey Kozlenkov Alexandra Keenan Yasmin L. Hurd Stella Dracheva Patrizia Casaccia Panos Roussos Bin Zhang |
author_facet |
Andrew T. McKenzie Minghui Wang Mads E. Hauberg John F. Fullard Alexey Kozlenkov Alexandra Keenan Yasmin L. Hurd Stella Dracheva Patrizia Casaccia Panos Roussos Bin Zhang |
author_sort |
Andrew T. McKenzie |
title |
Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
title_short |
Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
title_full |
Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
title_fullStr |
Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
title_full_unstemmed |
Brain Cell Type Specific Gene Expression and Co-expression Network Architectures |
title_sort |
brain cell type specific gene expression and co-expression network architectures |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/4f166a71fd834b69ad514d8d5441276a |
work_keys_str_mv |
AT andrewtmckenzie braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT minghuiwang braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT madsehauberg braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT johnffullard braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT alexeykozlenkov braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT alexandrakeenan braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT yasminlhurd braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT stelladracheva braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT patriziacasaccia braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT panosroussos braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures AT binzhang braincelltypespecificgeneexpressionandcoexpressionnetworkarchitectures |
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1718387935929171968 |