{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:58:52Z","timestamp":1789167532363,"version":"build-2803163510"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21GM150093, R21GM151703, R35155165"],"award-info":[{"award-number":["R21GM150093, R21GM151703, R35155165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neonatal sepsis remains a leading cause of global childhood mortality, yet treatment options are limited. Clinical and biological heterogeneity hinders the development of targeted therapies. Gene-expression profiling offers a potential strategy to identify neonatal sepsis subtypes and guide targeted intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed secondary analyses of publicly available gene-expression datasets. Differential gene expression analysis and T-distributed Stochastic Neighbor Embedding (t-SNE) identified biologically relevant patient clusters. Mortality and organ dysfunction were compared across clusters to determine clinical relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified three endotypes of neonatal sepsis based on the 100 gene expression mortality signature, distinguishing five non-survivors from 72 survivors across datasets. Compared with other endotypes, Endotype A was associated with high mortality (22% vs. 0%, p=0.003) and cardiac dysfunction (61% vs. 31%, p=0.025). Pathobiology among endotype A patients was primarily driven by neutrophil progenitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gene-expression profiling can be used to disentangle neonatal sepsis heterogeneity. Dysregulated hyperinflammatory response with emergency granulopoiesis was pathognomonic of high-risk endotype A. Pending further validation, gene-expression-based subclassification may be used to identify at-risk neonates and inform the selection of targeted sepsis therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1601316","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T01:31:55Z","timestamp":1750987915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic mortality signature defines high-risk neonatal sepsis endotype"],"prefix":"10.3389","volume":"16","author":[{"given":"Faris N.","family":"Al Gharaibeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Wynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishikesan","family":"Kamaleswaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihir R.","family":"Atreya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001502","article-title":"Risk of early-onset neonatal infection with maternal infection or colonization: A global systematic review and meta-analysis","volume":"10","author":"Chan","year":"2013","journal-title":"PloS Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2703","DOI":"10.3390\/jcm12072703","article-title":"Patterns of infections among extremely preterm infants","volume":"12","author":"Perez","year":"2023","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2022-058813","article-title":"Late-Onset sepsis among very preterm infants","volume":"150","author":"Flannery","year":"2022","journal-title":"Pediatrics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1741-7015-7-34","article-title":"Identification of pediatric septic shock subclasses based on genome-wide expression profiling","volume":"7","author":"Wong","year":"2009","journal-title":"BMC Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1864OC","article-title":"Developing a clinically feasible personalized medicine approach to pediatric septic shock","volume":"191","author":"Wong","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00046-1","article-title":"Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study","volume":"4","author":"Davenport","year":"2016","journal-title":"Lancet Respir Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30294-1","article-title":"Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study","volume":"5","author":"Scicluna","year":"2017","journal-title":"Lancet Respir Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201807-1419OC","article-title":"Transcriptomic signatures in sepsis and a differential response to steroids. 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