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Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C.
Pubmed ID: 34381049 RIS Download
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Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
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View all literature mentionsA cloud-based platform which allows users to analyze, visualize, and archive multiparamter cytometry data for single-cell biology. Multiple single-cell data sets can be analyzed and visualized simultaneously with a variety of graphics, inlcuding Sunburst, SPADE, and viSNE. Users can store and back up related data such as protocols, microscopy images, and presentations and collaborate and share analysis and data sets with other Cytobank users. Cytobank also provides a variety of services and training sessions to assist with experiment workflow.
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View all literature mentionsHuman and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.
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View all literature mentionsCell line Caco-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
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