Journal Article

Brain Cell Type Specific Gene Expression and Co-expression Network Architectures

Hauberg, Mads E., Fullard, John F., McKenzie, Andrew T., Kozlenkov, Alexey, Hurd, Yasmin L., Zhang, Bin, Roussos, Panos, Wang, Minghui, Casaccia, Patrizia, Keenan, Alexandra, Dracheva, Stella

2018

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 631/114/116/1925 / 631/378/116/1925 / Animals / Brain / Databases, Nucleic Acid / Datasets / Datasets as Topic / Endothelial Cells - cytology / Endothelial Cells - metabolism / Female / Gene expression / Gene Expression Profiling / Gene Regulatory Networks / Genetic Markers / Humanities and Social Sciences / Humans / Kinases / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Neuroglia - cytology / Neuroglia - metabolism / Neurons - cytology / Neurons - metabolism / Ribonucleic acid / RNA / Science / Single-Cell Analysis / Temporal Lobe - cytology / Temporal Lobe - metabolism / Transcriptome / Transcriptomes