title: Validation of Immune Cell Modules in Multicellular Transcriptomic Data.
abstract: Numerous gene signatures, or modules have been described to evaluate the immune cell composition in transcriptomes of multicellular tissue samples. However, significant diversity in module gene content for specific cell types is associated with heterogeneity in their performance. In order to rank modules that best reflect their purported association, we have generated the modular discrimination index (MDI) score that assesses expression of each module in the target cell type relative to other cells. We demonstrate that MDI scores predict modules that best reflect independently validated differences in cellular composition, and correlate with the covariance between cell numbers and module expression in human blood and tissue samples. Our analyses demonstrate that MDI scores provide an ordinal summary statistic that reliably ranks the accuracy of gene expression modules for deconvolution of cell type abundance in transcriptional data.
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Gabriele
authors.identifier: http://orcid.org/0000-0001-5772-0322
authors.initials: G
authors.lastname: Pollara
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Murray
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: Heather
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Byng-Maddick
authors.affiliation: UCL Advanced Diagnostics, University College London, London, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: Guppy
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Carolin T
authors.initials: CT
authors.lastname: Turner
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Chain
authors.affiliation: Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Mahdad
authors.initials: M
authors.lastname: Noursadeghi
mesh_terms: D002452:Cell Count; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology*