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Cross-laboratory analysis of brain cell type transcriptomes with applications to interpretation of bulk tissue data

B. Ogan Mancarci, Lilah Toker, Shreejoy J Tripathy, Brenna Li, Brad Rocco, Etienne Sibille, Paul Pavlidis
doi: https://doi.org/10.1101/089219
B. Ogan Mancarci
1Graduate Program in Bioinformatics, University of British Columbia, Vancouver, Canada
2Department of Psychiatry, University of British Columbia, Vancouver, Canada
3Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
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Lilah Toker
2Department of Psychiatry, University of British Columbia, Vancouver, Canada
3Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
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Shreejoy J Tripathy
2Department of Psychiatry, University of British Columbia, Vancouver, Canada
3Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
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Brenna Li
2Department of Psychiatry, University of British Columbia, Vancouver, Canada
3Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
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Brad Rocco
4Campbell Family Mental Health Research Institute of CAMH
5Department of Psychiatry and the Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
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Etienne Sibille
4Campbell Family Mental Health Research Institute of CAMH
5Department of Psychiatry and the Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
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Paul Pavlidis
2Department of Psychiatry, University of British Columbia, Vancouver, Canada
3Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
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  • For correspondence: [email protected]
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Abstract

Establishing the molecular diversity of cell types is crucial for the study of the nervous system. We compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single cell RNA-sequencing studies. We used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. We further demonstrate that summarized expression of marker gene sets in bulk tissue data can be used to estimate the relative cell type abundance across samples. To facilitate use of this expanding resource, we provide a user-friendly web interface at Neuroexpresso.org.

Significance Statement Cell type markers are powerful tools in the study of the nervous system that help reveal properties of cell types and acquire additional information from large scale expression experiments. Despite their usefulness in the field, known marker genes for brain cell types are few in number. We present NeuroExpresso, a database of brain cell type specific gene expression profiles, and demonstrate the use of marker genes for acquiring cell type specific information from whole tissue expression. The database will prove itself as a useful resource for researchers aiming to reveal novel properties of the cell types and aid both laboratory and computational scientists to unravel the cell type specific components of brain disorders.

Footnotes

  • Conflict of interest: The authors declare no competing financial interests

  • Funding sources: This work is supported by a NeuroDevNet grant to PP, the UBC bioinformatics graduate training program (BOM), a CIHR post-doctoral fellowship to SJT, by the Campbell Family Mental Health Research Institute of CAMH (ES and BR), NIH grants MH077159 to ES, and MH111099 and GM076990 to PP, and an NSERC Discovery Grant to PP.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 10, 2017.
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Cross-laboratory analysis of brain cell type transcriptomes with applications to interpretation of bulk tissue data
B. Ogan Mancarci, Lilah Toker, Shreejoy J Tripathy, Brenna Li, Brad Rocco, Etienne Sibille, Paul Pavlidis
bioRxiv 089219; doi: https://doi.org/10.1101/089219
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Cross-laboratory analysis of brain cell type transcriptomes with applications to interpretation of bulk tissue data
B. Ogan Mancarci, Lilah Toker, Shreejoy J Tripathy, Brenna Li, Brad Rocco, Etienne Sibille, Paul Pavlidis
bioRxiv 089219; doi: https://doi.org/10.1101/089219

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