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To address complicating heterogeneity in sepsis pathobiology, and improve outcomes, promising precision medicine approaches are helping identify disease endotypes, however, they require a more complete definition of sepsis subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we use RNA sequencing from peripheral blood to interrogate the host response to sepsis from participants in a global observational study carried out in West Africa, Southeast Asia, and North America (N\u2009=\u2009494).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identify four sepsis subtypes differentiated by 28-day mortality. A low mortality\n                      <jats:italic>immunocompetent<\/jats:italic>\n                      group is specified by features that describe the adaptive immune system. In contrast, the three high mortality groups show elevated clinical severity consistent with multiple organ dysfunction. The\n                      <jats:italic>immunosuppressed<\/jats:italic>\n                      group members show signs of a dysfunctional immune response, the\n                      <jats:italic>acute-inflammation<\/jats:italic>\n                      group is set apart by molecular features of the innate immune response, while the\n                      <jats:italic>immunometabolic<\/jats:italic>\n                      group is characterized by metabolic pathways such as heme biosynthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis reveals details of molecular endotypes in sepsis that support immunotherapeutic interventions and identifies biomarkers that predict outcomes in these groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-024-00542-7","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T11:03:35Z","timestamp":1718708615000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Sepsis endotypes identified by host gene expression across global cohorts"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9693-5010","authenticated-orcid":false,"given":"Josh G.","family":"Chenoweth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Brandsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Striegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3316-5659","authenticated-orcid":false,"given":"Pavol","family":"Genzor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Chiyka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramaniam","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Dogbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Boakye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary B.","family":"Fogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-2042","authenticated-orcid":false,"given":"Ephraim L.","family":"Tsalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-2453","authenticated-orcid":false,"given":"Christopher W.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Owusu-Ofori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Oppong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Oduro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te","family":"Vantha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Letizia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmagne G.","family":"Beckett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Schully","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle V.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"542_CR1","doi-asserted-by":"crossref","unstructured":"Singer, M. et al. 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Jackson Foundation for the Advancement of Military Medicine, Inc., on the identification of molecular endotypes that predict sepsis mortality. E.L.T is an employee and has equity in Danaher. E.L.T and C.W.W have received consulting fees from Biomeme. All other authors have no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"120"}}