Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29119244", "kind": "science-record", "revision": 7, "content_hash": "sha256:cdb8a7c6d748e5eafcd54a86a5702b10700cd267522d2cd36ff6ce70ffc973e2", "created_at": "2026-11-01T15:40:29Z", "updated_at": "2026-11-01T22:43:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes.", "doi": "10.1007/s00125-017-4460-7", "pmid": "29119244", "authors": ["Niina Lietzen", "Le T T An", "Maria K Jaakkola", "Henna Kallionpää", "Sami Oikarinen", "Juha Mykkänen", "Mikael Knip", "Riitta Veijola", "Jorma Ilonen", "Jorma Toppari", "Heikki Hyöty", "Riitta Lahesmaa", "Laura L Elo"], "journal": "Diabetologia", "year": 2018, "abstract": "AIMS/HYPOTHESIS: Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes.\nMETHODS: Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals.\nRESULTS: Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed.\nCONCLUSIONS/INTERPRETATION: We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.\nDATA AVAILABILITY: The datasets analysed during the current study are included in this published article and its supplementary information files ( www.btk.fi/research/computational-biomedicine/1234-2 ) or are available from the Gene Expression Omnibus (GEO) repository (accession GSE30211).", "claims": [{"id": "claim-method", "statement": "The z score profiles were clustered separately for each child using the k-means algorithm, with Pearson correlation and k = 10.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29119244", "locator": "sections[4] \"Microarray data processing and clustering\" paragraph 3", "quote": "The z score profiles were clustered separately for each child using the k-means algorithm, with Pearson correlation and k = 10."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are included in this published article and its supplementary information files (www.btk.fi/research/computational-biomedicine/1234-2) or are available from the GEO repository (accession GSE30211).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29119244", "locator": "sections[15] \"notes\" paragraph 1", "quote": "The datasets analysed during the current study are included in this published article and its supplementary information files (www.btk.fi/research/computational-biomedicine/1234-2) or are available from the GEO repository (accession GSE30211)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Genome-wide transcriptomics of longitudinal whole-blood samples was used to build a 339-gene enterovirus-induced signature, including 77 genes upregulated in human peripheral blood mononuclear cells infected in vitro with three different enteroviruses; the source datasets are available from GEO accession GSE30211.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29119244", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA."}, {"asset": "source:pmid:29119244", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses."}, {"asset": "source:pmid:29119244", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "The datasets analysed during the current study are included in this published article and its supplementary information files (www.btk.fi/research/computational-biomedicine/1234-2) or are available from the Gene Expression Omnibus (GEO) repository (accession GSE30211)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Genome-wide transcriptomics of longitudinal whole-blood samples was used to build a 339-gene enterovirus-induced signature, including 77 genes upregulated in human peripheral blood mononuclear cells infected in vitro with three different enteroviruses; the source datasets are available from GEO accession GSE30211.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29119244"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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