Deep learning-based clustering robustly identified two classes of sepsis with both prognostic and predictive values.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33181462", "kind": "science-record", "revision": 8, "content_hash": "sha256:67523856a57146be80998fcff08200a6b1d2183923518e55c0c8bf95e8e38469", "created_at": "2026-11-01T15:41:15Z", "updated_at": "2026-11-01T22:45:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deep learning-based clustering robustly identified two classes of sepsis with both prognostic and predictive values.", "doi": "10.1016/j.ebiom.2020.103081", "pmid": "33181462", "authors": ["Zhongheng Zhang", "Qing Pan", "Huiqing Ge", "Lifeng Xing", "Yucai Hong", "Pengpeng Chen"], "journal": "EBioMedicine", "year": 2020, "abstract": "BACKGROUND: Sepsis is a heterogenous syndrome and individualized management strategy is the key to successful treatment. Genome wide expression profiling has been utilized for identifying subclasses of sepsis, but the clinical utility of these subclasses was limited because of the classification instability, and the lack of a robust class prediction model with extensive external validation. The study aimed to develop a parsimonious class model for the prediction of class membership and validate the model for its prognostic and predictive capability in external datasets.\nMETHODS: The Gene Expression Omnibus (GEO) and ArrayExpress databases were searched from inception to April 2020. Datasets containing whole blood gene expression profiling in adult sepsis patients were included. Autoencoder was used to extract representative features for k-means clustering. Genetic algorithms (GA) were employed to derive a parsimonious 5-gene class prediction model. The class model was then applied to external datasets (n = 780) to evaluate its prognostic and predictive performance.\nFINDINGS: A total of 12 datasets involving 1613 patients were included. Two classes were identified in the discovery cohort (n = 685). Class 1 was characterized by immunosuppression with higher mortality than class 2 (21.8% [70/321] vs. 12.1% [44/364]; p < 0.01 for Chi-square test). A 5-gene class model (C14orf159, AKNA, PILRA, STOM and USP4) was developed with GA. In external validation cohorts, the 5-gene class model (AUC: 0.707; 95% CI: 0.664 - 0.750) performed better in predicting mortality than sepsis response signature (SRS) endotypes (AUC: 0.610; 95% CI: 0.521 - 0.700), and performed equivalently to the APACHE II score (AUC: 0.681; 95% CI: 0.595 - 0.767). In the dataset E-MTAB-7581, the use of hydrocortisone was associated with increased risk of mortality (OR: 3.15 [1.13, 8.82]; p = 0.029) in class 2. The effect was not statistically significant in class 1 (OR: 1.88 [0.70, 5.09]; p = 0.211).\nINTERPRETATION: Our study identified two classes of sepsis that showed different mortality rates and responses to hydrocortisone therapy. Class 1 was characterized by immunosuppression with higher mortality rate than class 2. We further developed a 5-gene class model to predict class membership.\nFUNDING: The study was funded by the National Natural Science Foundation of China (Grant No. 81,901,929).", "claims": [{"id": "claim-method", "statement": "Over- or under-expressed genes were analysed using the limma package and visualized with volcano plot [32].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33181462", "locator": "sections[8] \"Functional analysis of the two classes\" paragraph 2", "quote": "Over- or under-expressed genes were analysed using the limma package and visualized with volcano plot [32]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data were available in publicly accessible databases. Accession numbers were available in Table 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33181462", "locator": "sections[26] \"Data Sharing Statement\" paragraph 2", "quote": "All data were available in publicly accessible databases. 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CAP diagnosis was based on International Sepsis Forum Consensus Conference definition.", "Sepsis due to CAP and HAP + non-infectious control", "On ICU admission", "Netherlands and UK", "28-day", "114/802"], ["GSE54514", "Sepsis was defined as documented bacterial infection in addition to the presence of at least two of the following four clinical criteria: (a) fever or hypothermia (temperature > 38 °C or < 36 °C); (b) tachycardia (>90 beats/min); (c) tachypnea (>20 breaths/min or PaCO2 < 32 mmHg) or the need for mechanical ventilation; (d) an altered white blood cell count of more than 12,000 cells/μL, less than 4000 cells/μL, or the presence of more than 10% band forms", "Sepsis", "In 24 h of ICU admission", "Australia", "ICU stay", "9/53"], ["GSE63042", "Adults at the ED with known or suspected acute infection and presence of at least two SIRS criteria", "Sepsis in CAPSOD study", "Day of enrollment upon presentation to the ED", "United States", "28-day", "28/106"], ["GSE95233", "Septic shock as defined by a systolic blood pressure of <90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour.", "Septic shock", "Day 1 of ICU admission", "France", "28-day", "34/102"], ["GSE106878", "Septic shock as defined by a systolic blood pressure of <90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour.", "Hydrocortisone application in septic shock", "Before hydrocortisone application", "International", "28-day", "13/47"], ["GSE33119", "Septic shock", "activated protein C in septic shock", "12 hrs after diagnosis", "France", "NA", "10/20"], ["GSE48080", "Patients older than 18 years were enrolled within 48 hrs of the first occurrence of organ dysfunction indicative of severe sepsis or septic shock.", "severe sepsis or septic shock", "Day 0", "Brazil", "NA", "5/10"], ["GSE33118", "Septic shock with a systolic blood pressure of <90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour.", "NA", "Day 0", "France", "NA", "10/20"]], "row_count": 13, "column_count": 7, "numeric_cells": 43, "header_rows": 1, "locator": "section[14]/table-wrap[1]#tbl0001"}}, {"id": "asset:table:pmid:33181462:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:14a1d6de2bcd69255ff15d87cf2bf71e5a94a56912ca11e933814998dd390356", "bytes": 3749, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#tbl0001", "version": null, "note": "Dataset included in the study.", "structure": {"pmcid": "PMC7658497", "section_index": 14, "section_title": "Datasets", "row_count": 13, "column_count": 7}, "table": {"label": "Table 1", "caption": "Dataset included in the study.", "rows": [["Accession", "Study population/Inclusion criteria", "Cohort description", "Timing of gene expression profiling", "Country", "Timing of mortality", "Mortality/Total sample"], ["E-MTAB-7581", "Clinical evidence of infection, evidence of a systemic response to infection, and the onset of shock within the previous 72 h (as defined by a systolic blood pressure of <90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour) and hypoperfusion or organ dysfunction attributable to sepsis.", "Post-hoc of an RCT comparing Vasopressin vs. Norepinephrine for septic shock", "At enrollment", "United Kingdom", "28-day", "48/176"], ["E-MTAB-5274", "Sepsis defined by ACCP/SCCM guidelines. FP was diagnosed at laparotomy as inflammation of the peritoneal membrane secondary to large bowel perforation and fecal contamination.", "Sepsis due to FP", "First day of ICU stay", "UK", "28-day", "14/108"], ["E-MTAB-5273", "CAP was defined as a febrile illness associated with a cough, sputum production, breathlessness, leukocytosis and radiological features of pneumonia, acquired in the community or within two days of ICU admission.", "Sepsis due to CAP, GAinS", "First day of ICU stay", "UK", "28-day", "22/118"], ["E-MTAB-4451", "The diagnosis of sepsis was based on the International Consensus Criteria with all patients reported here showing some degree of organ dysfunction during ICU admission.", "Sepsis due to CAP", "On ICU admission", "UK", "28-day", "57/114"], ["GSE65682", "ICU patients with suspected CAP for which the attending physician started antibiotic therapy. CAP diagnosis was based on International Sepsis Forum Consensus Conference definition.", "Sepsis due to CAP and HAP + non-infectious control", "On ICU admission", "Netherlands and UK", "28-day", "114/802"], ["GSE54514", "Sepsis was defined as documented bacterial infection in addition to the presence of at least two of the following four clinical criteria: (a) fever or hypothermia (temperature > 38 °C or < 36 °C); (b) tachycardia (>90 beats/min); (c) tachypnea (>20 breaths/min or PaCO2 < 32 mmHg) or the need for mechanical ventilation; (d) an altered white blood cell count of more than 12,000 cells/μL, less than 4000 cells/μL, or the presence of more than 10% band forms", "Sepsis", "In 24 h of ICU admission", "Australia", "ICU stay", "9/53"], ["GSE63042", "Adults at the ED with known or suspected acute infection and presence of at least two SIRS criteria", "Sepsis in CAPSOD study", "Day of enrollment upon presentation to the ED", "United States", "28-day", "28/106"], ["GSE95233", 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