{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:09Z","timestamp":1790326989521,"version":"4.1.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Infants with SVHD in the interstage period were compared to similar-age healthy controls. Serum samples were collected, stored at \u221280\u00b0C, and run on a panel of 1,500 proteins in single batch analysis (Somalogic Inc., CO). Partial Least Squares-Discriminant Analysis (PLS-DA) was used to compare the proteomic profile of cases and controls and t-tests to detect differences in individual proteins (FDR &amp;lt;0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PLS-DA readily discriminated between SVHD cases (<jats:italic>n<\/jats:italic>\u2009=\u200933) and controls (<jats:italic>n<\/jats:italic>\u2009=\u200924) based on their proteomic pattern alone (Accuracy\u2009=\u20090.96, <jats:italic>R<\/jats:italic><jats:sup>2\u2009<\/jats:sup>=\u20090.97, <jats:italic>Q<\/jats:italic><jats:sup>2\u2009<\/jats:sup>=\u20090.80). 568 proteins differed between groups (FDR &amp;lt;0.05). We identified 25 up-regulated functional clusters and 13 down-regulated. Active biological systems fell into six key groups: angiogenesis and cell proliferation\/turnover, immune system activation and inflammation, altered metabolism, neural development, gastrointestinal system, and cardiac physiology and development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with &amp;gt;500 circulating proteins distinguishing the groups. These proteomic data identify widespread protein dysregulation across multiple biologic systems with promising biological plausibility as drivers of SVHD morbidity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1308700","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:31:34Z","timestamp":1702038694000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks"],"prefix":"10.3389","volume":"11","author":[{"given":"Lindsay M.","family":"Thomson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Mancuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly 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