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Strategies for cellular deconvolution in human brain RNA sequencing data

bioRxiv, ISSN: 2692-8205
2020
  • 6
    Citations
  • 0
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Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    6
    • Citation Indexes
      6
      • CrossRef
        6

Article Description

Statistical deconvolution strategies have emerged over the past decade to estimate the proportion of various cell populations in homogenate tissue sources like brain using gene expression data. Here we show that several existing deconvolution algorithms which estimate the RNA composition of homogenate tissue, relates to the amount of RNA attributable to each cell type, and not the cellular composition relating to the underlying fraction of cells. Incorporating “cell size” parameters into RNA-based deconvolution algorithms can successfully recover cellular fractions in homogenate brain RNA-seq data. We lastly show that using both cell sizes and cell type-specific gene expression profiles from brain regions other than the target/user-provided bulk tissue RNA-seq dataset consistently results in biased cell fractions. We report several independently constructed cell size estimates as a community resource and extend the MuSiC framework to accommodate these cell size estimates (https://github.com/xuranw/MuSiC/).

Bibliographic Details

Sosina, Olukayode A.; Tran, Matthew N; Maynard, Kristen R; Tao, Ran; Taub, Margaret A.; Martinowich, Keri; Semick, Stephen A.; Quach, Bryan C.; Weinberger, Daniel R.; Hyde, Thomas M.; Hancock, Dana B.; Kleinman, Joel E.; Leek, Jeffrey T; Jaffe, Andrew E

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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