Nucleic Acid Biomarker Panels for Early Sepsis Prediction
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Solution Overview
Problem
Current diagnostic assays for sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, lack reliable biomarkers with high predictive accuracy, especially for predicting the development of sepsis before symptoms appear, with most studies focusing on the previous definition of sepsis as systemic inflammatory response syndrome (SIRS) in response to infection.
Innovation Solution
Identification of specific nucleic acid markers, such as ACTR6, AFF1, ARID5B, and others, in a panel of 80 markers, capable of predicting infection and organ dysfunction with high predictive accuracy (AUC > 0.8) up to three days before symptoms, using mathematical models and biomarker signatures in biological samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If agent-specific assays are used to detect infection, then detection accuracy for specific pathogens is improved, but utility is limited because biological agents are absent or present at very low concentrations in clinical samples during initial stages of infection
Solution Approach 1:
The patent uses host biomarkers (intermediaries) that are produced in response to pathogen infection rather than detecting the pathogens directly. These host biomarkers serve as mediators that amplify the detectable signal when pathogen concentrations are too low for direct detection, thereby maintaining detection accuracy while improving reliability during early infection stages.
Solution Approach 2:
The patent transitions from detecting pathogen-specific parameters (presence/quantity of biological agents) to detecting host response parameters (expression levels of host biomarkers). This parameter change allows detection to remain accurate while becoming reliable even when pathogen concentrations are below detection thresholds.
2Ease of operation
If traditional sepsis definition (SIRS) is used, then diagnostic simplicity is improved, but predictive accuracy for life-threatening organ dysfunction is worsened
Solution Approach 1:
The patent segments the diagnostic process into two distinct parts: (1) a simple screening component using traditional SIRS criteria for ease of identification, and (2) a precision component using biomarker panels to accurately predict life-threatening organ dysfunction. This segmentation maintains diagnostic simplicity while improving predictive accuracy for severe outcomes.
Solution Approach 2:
The patent applies different diagnostic qualities to different clinical scenarios: traditional SIRS criteria provide adequate simplicity for initial screening, while biomarker-based prediction provides the necessary precision for identifying patients at risk of life-threatening organ dysfunction. Each diagnostic approach is optimized for its specific purpose.
3Measurement precision
If whole transcriptome analysis is used to distinguish patterns of gene expression, then diagnostic accuracy for infectious agents is improved, but device complexity and cost are worsened
Solution Approach 1:
The patent extracts only the most critical biomarkers from the complete transcriptome analysis. Instead of measuring all genes, the invention identifies and measures a specific subset of host biomarkers that provide sufficient diagnostic accuracy while dramatically reducing system complexity and cost.
Solution Approach 2:
The patent replaces complex, expensive whole transcriptome analysis systems with simpler, more affordable biomarker panels that can be implemented using standard clinical laboratory techniques. This substitution maintains adequate diagnostic accuracy while making the technology accessible for routine clinical use.
4Stability of the object's composition
If biomarker discovery relies on laboratory models of infection, then experimental control is improved, but fidelity to human disease pathogenesis is worsened
Solution Approach 1:
The patent creates a biomarker signature that copies the host response pattern observed in human sepsis patients. Rather than relying on laboratory models that may not faithfully reproduce human disease, the invention directly characterizes the biomarker profile in human patients and uses this authentic human response pattern for diagnosis and prediction.
Data Source
AI summary
The present invention is concerned with kits, methods and apparatus for analysing a biological sample from a subject to predict and/or monitor the development of infection and/or organ dysfunction and/or sepsis utilising groups of nucleic acid markers to predict the development of infection and/or organ dysfunction and/or sepsis.