{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294465"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part3]","description":"The central nervous system represents a uniquely immune-privileged environment, with inflammatory responses involving several resident CNS-specific cell types. While stereotyped cellular and transcriptional responses recur across varied diseases, relevant signaling pathways and regulatory networks are not fully understood. Here, we describe a screening platform based on high-throughput RNA-seq analysis and glial cell state gene set scores that enables multimodal investigation of inflammatory networks at scale. As proof-of-concept, we investigate genetically heterogeneous mice from a large-scale chemical mutagenesis screen to identify novel functionally relevant variants in six genes previously linked to human CNS disorders: Nrros, Ctsd, Smpd1, Idua, Nlrp1a, and Inpp5d . We leverage the rich and readily-interpretable data from our study to demarcate distinct inflammatory states arising from each mutation. In all, our work provides a methodology for discovering novel regulators of CNS neuroimmune homeostasis and provides a validated analysis framework for identifying discrete neuroinflammatory modules that are engaged divergently across disease 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