{"doi":"10.1093/jpids/piad035","title":"Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature","abstract":"BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.","journal":"Journal of the Pediatric Infectious Diseases Society","year":2023,"id":333885,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.939,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1061712,"name":"Luca Miglietta","orcid":"0000-0002-6652-4785","position":1,"is_corresponding":false},{"id":917384,"name":"Dominic Habgood-Coote","orcid":"0000-0001-5501-0335","position":2,"is_corresponding":false},{"id":1033036,"name":"Giselle D’Souza","orcid":"0000-0002-1020-7529","position":3,"is_corresponding":false},{"id":104782,"name":"Priyen Shah","orcid":"0000-0001-9164-8862","position":4,"is_corresponding":false},{"id":1062252,"name":"Samuel Nichols","orcid":null,"position":5,"is_corresponding":false},{"id":618020,"name":"Ortensia Vito","orcid":"0000-0001-5509-6351","position":6,"is_corresponding":false},{"id":1062253,"name":"Oliver Powell","orcid":null,"position":7,"is_corresponding":false},{"id":1062254,"name":"M. 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