{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:30:48Z","timestamp":1778859048054,"version":"3.51.4"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Sepsis is a life-threatening condition mainly caused by gram-negative and gram-positive bacteria. Understanding the type of causative agent in the early stages is essential for precise antibiotic therapy. This study sought to identify a host gene set capable of distinguishing between sepsis induced by gram-negative bacteria; <jats:italic>Escherichia coli<\/jats:italic> and gram-positive bacteria; <jats:italic>Staphylococcus aureus<\/jats:italic> in community-onset adult patients. In the present study, microarray expression information was used to apply the Least Absolute Shrinkage and Selection Operator (Lasso) technique to select the predictive gene set for classifying sepsis induced by <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> or <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> pathogens. We identified 25 predictive genes, including <jats:italic>LILRA5<\/jats:italic> and <jats:italic>TNFAIP6<\/jats:italic>, which had previously been associated with sepsis in other research. Using these genes, we trained a logistic regression classifier to distinguish whether a sample contains an <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> or <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infection or belongs to a healthy control group, and subsequently assessed its performance. The classifier achieved an Area Under the Curve (AUC) of 0.96 for <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and 0.98 for <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>-induced sepsis, and perfect discrimination (AUC of 1) for healthy controls from the other conditions in a 10-fold cross-validation. The genes demonstrated an AUC of 0.75 in distinguishing between sepsis patients with <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> pathogens. These findings were further confirmed in two distinct independent validation datasets which gave high prediction AUC ranging from 0.72\u20130.87 and 0.62 in distinguishing three groups of participants and two groups of patients respectively. These genes were significantly enriched in the immune system, cytokine signaling in immune system, innate immune system, and interferon signaling. Transcriptional patterns in blood can differentiate patients with <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>-induced sepsis from those with <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>-induced sepsis. These diagnostic markers, upon validation in larger trials, may serve as a foundation for a reliable differential diagnostics assay.<\/jats:p>","DOI":"10.1371\/journal.pone.0305920","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T17:38:46Z","timestamp":1720201126000},"page":"e0305920","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptional markers classifying Escherichia coli and Staphylococcus aureus induced sepsis in adults: A data-driven approach"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4546-8948","authenticated-orcid":true,"given":"Mahnaz","family":"Irani Shemirani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"pone.0305920.ref001","unstructured":"World Health Organization. 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