{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:33Z","timestamp":1792788813348,"version":"4.5.0"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2024A03J0052"],"award-info":[{"award-number":["2024A03J0052"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Elite Clinical Technical Talent Program of Guangdong Provincial Hospital of Chinese Medicine","id":[{"id":"https:\/\/ror.org\/01gb3y148","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome and Science and Technology Planning Project of Guangdong Province","award":["2023B1212060063"],"award-info":[{"award-number":["2023B1212060063"]}]},{"name":"the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine","award":["20264020"],"award-info":[{"award-number":["20264020"]}]},{"name":"the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine","award":["20251174"],"award-info":[{"award-number":["20251174"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe acute pancreatitis (SAP) is associated with persistent organ failure and substantial mortality, yet the transcriptomic mechanisms underlying progression from mild acute pancreatitis to severe-spectrum disease remain incompletely defined. Early identification of patients at risk of persistent organ failure remains an important unmet clinical need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrative transcriptomic analysis of peripheral blood RNA-seq data from GSE194331 (healthy controls [HC], n\u2009=\u200932; mild acute pancreatitis [MAP], n\u2009=\u200957; severe-spectrum AP group [SAP group], n\u2009=\u200930, comprising MSAP n\u2009=\u200920 and severe AP n\u2009=\u200910; sampled within 24 hours of admission). A dual-comparison framework was established using SAP vs HC and SAP vs MAP to distinguish broad AP-associated changes from organ failure-associated features. Gene set enrichment analysis (GSEA), ssGSEA-based immune signature analysis, triple-algorithm machine learning (LASSO, random forest, and SVM-RFE), and weighted gene co-expression network analysis (WGCNA) were integrated to identify candidate genes and characterize associated biological programs. Cross-species single-cell RNA-seq data from rat ileal tissue (GSE244963) were used only as supportive cell-type context for candidate genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GSEA identified enrichment of NETosis, complement\/coagulation, oxidative phosphorylation, and multiple inflammatory cell death-related programs in the SAP group. ssGSEA revealed reduced adaptive immune-associated signatures, with CD8\u2009+\u2009T-cell and NK-cell signatures already reduced in MAP and CD4\u2009+\u2009T-cell and Treg-associated signatures showing additional reduction in SAP relative to MAP. Triple-algorithm machine learning identified three core candidate genes with discovery-cohort AUC values: MRPL51 (ML-A, SAP vs HC, AUC\u2009=\u20090.951), C1QA (ML-B, SAP vs MAP, AUC\u2009=\u20090.754), and DACT1 (ML-B, SAP vs MAP, AUC\u2009=\u20090.758). Repeated stratified 5-fold cross-validation supported internal stability of the single-gene estimates, but no independent external validation cohort was available. A neutrophil-associated NETosis gene triad (OLFM4, LTF, and CEACAM6) was additionally co-selected by LASSO and random forest in ML-B. Rat ileal scRNA-seq provided supportive, cross-species cell-type context rather than definitive validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integrative transcriptomic analysis of peripheral blood identifies candidate transcriptomic markers and suggests neutrophil-associated, metabolic, and adaptive immune programs associated with AP severity progression. The stratified adaptive immune signature reduction pattern and the NETosis-associated gene triad may represent discovery-level transcriptomic features of progression from mild AP to the severe-spectrum AP group. Independent validation in prospective human cohorts is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0349692","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:37:41Z","timestamp":1790357861000},"page":"e0349692","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative transcriptomic analysis of peripheral blood identifies NETosis-associated programs and a stratified adaptive immune suppression pattern in severe acute pancreatitis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-9240","authenticated-orcid":true,"given":"Yaobin","family":"He","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong Province, China"],"department":["Department of Abdominal 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Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong Province, China"],"department":["Department of Abdominal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-184X","authenticated-orcid":true,"given":"Youxing","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong Province, China"],"department":["Department of Abdominal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"1","key":"pone.0349692.ref001","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S2468-1253(16)30004-8","article-title":"Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort 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