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pmid:27681387
Benchmarking Sepsis Gene Expression Diagnostics Using Public Data.
Timothy E Sweeney · Purvesh Khatri
Critical care medicine · 2017 doi:10.1097/CCM.0000000000002021
Paper
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Experiment
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Data
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Analysis
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Complete file
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We performed a systematic search for publicly available gene expression data in sepsis and tested each gene expression classifier in all included datasets. We also created a public repository of sepsis gene expression data to encourage their future reuse.\nDATA SOURCES: We searched National Institutes of Health Gene Expression Omnibus and EBI ArrayExpress for human gene expression microarray datasets. We also included the Glue Grant trauma gene expression cohorts.\nSTUDY SELECTION: We selected clinical, time-matched, whole blood studies of sepsis and acute infections as compared to healthy and/or noninfectious inflammation patients. We identified 39 datasets composed of 3,241 samples from 2,604 patients.\nDATA EXTRACTION: All data were renormalized from raw data, when available, using consistent methods.\nDATA SYNTHESIS: Mean validation areas under the receiver operating characteristic curve for discriminating septic patients from patients with noninfectious inflammation for the Sepsis MetaScore, the FAIM3-to-PLAC8 ratio, and the Septicyte Lab were 0.82 (range, 0.73-0.89), 0.78 (range, 0.49-0.96), and 0.73 (range, 0.44-0.90), respectively. Paired-sample t tests of validation datasets showed no significant differences in area under the receiver operating characteristic curves. Mean validation area under the receiver operating characteristic curves for discriminating infected patients from healthy controls for the Sepsis MetaScore, FAIM3-to-PLAC8 ratio, and Septicyte Lab were 0.97 (range, 0.85-1.0), 0.94 (range, 0.65-1.0), and 0.71 (range, 0.24-1.0), respectively. There were few significant differences in any diagnostics due to pathogen type.\nCONCLUSIONS: The three diagnostics do not show significant differences in overall ability to distinguish noninfectious systemic inflammatory response syndrome from sepsis, though the performance in some datasets was low (area under the receiver operating characteristic curve, < 0.7) for the FAIM3-to-PLAC8 ratio and Septicyte Lab. The Septicyte Lab also demonstrated significantly worse performance in discriminating infections as compared to healthy controls. 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