Systems and methods for characterizing sepsis
Inventors
Hecker, Louise • Slepian, Marvin J. • BIME, Christian • Zhou, Tong • Wang, Ting
Assignees
US Department of Veterans Affairs • University of Arizona
Publication Number
US-11230735-B2
Publication Date
2022-01-25
Expiration Date
2036-12-23
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Abstract
The present disclosure relates to methods of characterizing disease. In particular, this invention relates to methods for selecting a treatment, treating, and predicting survival time in subjects suffering from sepsis, based on the characterization of genes associated with a reactive oxygen species (ROS) molecular signature.
Core Innovation
The present invention relates to methods for characterizing disease, specifically sepsis, by selecting treatment, treating, and predicting survival time in subjects suffering from sepsis. This is based on the characterization of genes associated with a reactive oxygen species (ROS) molecular signature.
The problem being solved is the lack of reliable ROS-associated biomarkers and diagnostics which define mortality or predict survival in sepsis. Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units, and current biomarkers do not effectively predict survival or facilitate individualized therapies.
The invention identifies a 21-gene ROS-associated molecular signature predictive of survival in septic patients, validated across distinct patient populations. This signature outperforms randomly generated gene signatures of the same size, confirming the critical role of ROS in sepsis pathogenesis. The signature enables the use of peripheral blood molecular profiles as biomarkers to predict mortality risk and facilitate personalized treatment.
Claims Coverage
The patent contains two independent claims focusing on methods for determining risk of death from sepsis and monitoring treatment effectiveness using gene expression analysis of ROS-associated genes.
Method of determining risk of death from sepsis based on gene expression levels
A method comprising obtaining a biological sample (whole blood, plasma, serum, or urine) from a subject with sepsis, detecting expression levels of 21 specified genes by polymerase chain reaction and comparing these levels to those of subjects without sepsis, calculating a risk score as a linear combination of gene expression values, and predicting risk of death from sepsis based on this score.
Method of monitoring sepsis treatment effectiveness by gene expression profiling
A method involving obtaining biological samples from a subject being treated for sepsis, determining gene expression levels of the same 21 genes by PCR, comparing them to reference gene expression levels from subjects without sepsis or with non-life threatening sepsis, calculating a risk score, and identifying a favorable treatment response if the risk score approximates that of non-severe subjects or decreases after treatment.
The independent claims cover methods of predicting mortality risk in sepsis and monitoring treatment efficacy using detection and quantitation of expression levels of a specific 21-gene ROS-associated signature and calculating a risk score to inform clinical outcomes.
Stated Advantages
The gene signature predicts survival in septic patients, enabling prognosis.
The signature is validated across diverse patient cohorts, establishing reliability.
The approach facilitates personalized therapies by identifying mortality risk based on ROS gene expression.
The gene signature outperforms randomly generated signatures, indicating true biological relevance.
Documented Applications
Predicting survival time for human subjects suffering from sepsis.
Monitoring treatment response in human subjects with sepsis.
Characterizing sepsis based on altered gene expression for diagnosis or risk stratification.
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