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Novel approaches to biomarker discovery that are currently being investigated include combination biomarkers, host 'sepsis signatures' based on differential gene expression, site-specific biomarkers, biomechanical assays, and incorporation of new and pre-existing host biomarkers into machine learning algorithms. To date, no single reliable independent biomarker of infection exists. Whilst new approaches to biomarker discovery hold promise, their clinical utility may be limited if previous mistakes that have afflicted sepsis biomarker re