RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types

通过mRNA丰度归一化的RNA-Seq特征可以实现人类免疫细胞类型的绝对解卷积

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作者:Gianni Monaco ,Bernett Lee ,Weili Xu ,Seri Mustafah ,You Yi Hwang ,Christophe Carré ,Nicolas Burdin ,Lucian Visan ,Michele Ceccarelli ,Michael Poidinger ,Alfred Zippelius ,João Pedro de Magalhães ,Anis Larbi

Abstract

The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 immune cell types within the peripheral blood mononuclear cell (PBMC) fraction of healthy donors using RNA-seq (RNA sequencing) and flow cytometry. Our dataset was used, first, to identify sets of genes that are specific, are co-expressed, and have housekeeping roles across the 29 cell types. Then, we examined differences in mRNA heterogeneity and mRNA abundance revealing cell type specificity. Last, we performed absolute deconvolution on a suitable set of immune cell types using transcriptomics signatures normalized by mRNA abundance. Absolute deconvolution is ready to use for PBMC transcriptomic data using our Shiny app (https://github.com/giannimonaco/ABIS). We benchmarked different deconvolution and normalization methods and validated the resources in independent cohorts. Our work has research, clinical, and diagnostic value by making it possible to effectively associate observations in bulk transcriptomics data to specific immune subsets.

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