Supplement to Mancarci et al. (NeuroExpresso)

Supplement to Cross-laboratory analysis of brain cell type expression profiles with applications to bulk brain tissue transcriptome interpretation

B. Ogan Mancarci, Lilah Toker, Shreejoy Tripathy, Brenna Li, Brad Rocco, Etienne Sibille, Paul Pavlidis

Published in eNeuro

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. Using this approach, we show that majority of genes previously reported as differentially expressed in Parkinson’s disease can be attributed to the reduction in dopaminergic cell number rather than regulatory events. To facilitate use of this expanding resource, we provide a user-friendly web interface at Neuroexpresso.org.

Contact

paul@chibi.ubc.ca

Supplemental Materials

  1. Web application at neuroexpresso.org
  2. Code for analysis at github.com/oganm/neuroExpressoAnalysis
  3. R package for marker gene selection and marker gene profile estimation (includes marker gene list) github.com/oganm/markerGeneProfile
  4. List of marker genes (gene symbols). Three lists are available.
    1. mouseMarkerGenes. Genes selected by  combining pyramidal sub-types into a single group (JSON, TSV, Rdata, Excel, RAR).
    2. pyramidalDeep. Genes selected by considering pyramidal sub-types as distinct cell types (JSON, TSV, Rdata, Excel, RAR).
    3. Combined. mouseMarkerGenes with pan-pyramidal gene list from pyramidalDeep included. This list is used in downstream analysis in the paper (JSON, TSV, Rdata, Excel, RAR).
  5. List of marker genes (NCBI ids)
    1. mouseMarkerGenes (JSONTSV, Rdata , Excel)
    2. pyramidalDeep (JSONTSVRdata, Excel)
    3. Combined (JSON, TSVRdata, Excel)
  6. Validation of purkinje and granule cell markers: Supplement
  7. NeuroExpresso gene expression data
    1. Microarrays:
      1. Text: Design (tsv), Expression (csv)
      2. Rdata: Design, Expression
    2. RNA-seq
      1. Text (original source): Design (clustering results) (csv), Expression (rpkm) (csv)
      2. Text (processed for NeuroExp.-reordered, genes with 0 expression removed): Design (tsv), Expression (csv.gz)
      3. Rdata: Design, Expression