Diagnosis of sepsis or SIRS using biomarker profiles
First Claim
1. A method of determining the status of sepsis in an individual, comprising:
- (a) obtaining a first biomarker profile from a first biological sample taken from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from a reference population, wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population;
wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison determines the status of sepsis in the individual.
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Abstract
The early prediction or diagnosis of sepsis advantageously allows for clinical intervention before the disease rapidly progresses beyond initial stages to the more severe stages, such as severe sepsis or septic shock, which are associated with high mortality. Early prediction or diagnosis is accomplished by comparing an individual'"'"'s profile of biomarker expression to profiles obtained from one or more control, or reference, populations, which may include a population who develops sepsis. Recognition of features in the individual'"'"'s biomarker profile that are characteristic of the onset of sepsis allows a clinician to diagnose the onset of sepsis from a bodily fluid isolated at the individual at a single point in time. The necessity of monitoring the patient over a period of time is, therefore, avoided, advantageously allowing clinical intervention before the onset of serious symptoms. Further, because the biomarker expression is assayed for its profile, identification of the particular biomarkers is unnecessary. The comparison of an individual'"'"'s biomarker profile to biomarker profiles of appropriate reference populations likewise can be used to diagnose SIRS in the individual.
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Citations
64 Claims
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1. A method of determining the status of sepsis in an individual, comprising:
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(a) obtaining a first biomarker profile from a first biological sample taken from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from a reference population, wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population;
wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison determines the status of sepsis in the individual. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
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2. A method of determining the status of sepsis in an individual, comprising:
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(a) obtaining a first biomarker profile from a biological sample taken at a single point in time from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from a reference population, wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison of the biomarker profiles can determine the status of sepsis in the individual with an accuracy of at least about 60%.
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3. A method of determining the status of sepsis in an individual, comprising comparing (i) a first biomarker profile generated from a first biological sample taken from the individual at a single point in time with (ii) a biomarker profile generated from a reference population, wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons, and wherein the comparison comprises applying a decision rule that determines the status of sepsis in the individual.
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4. A method of determining the status of sepsis in an individual, comprising:
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(a) obtaining a first biomarker profile from a first biological sample taken from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from biological samples from a reference population, wherein the reference population is selected from the group consisting of a normal reference population, a SIRS-positive reference population, an infected/SIRS-negative reference population, a sepsis-positive reference population, a reference population at a stage in the progression of sepsis, a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 0-36 hours, a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 36-60 hours, and a SIRS-positive reference population confirmed as having sepsis by conventional techniques after about 60-84 hours;
wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population;
wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison determines the status of sepsis in the individual.
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5. A method of determining the status of sepsis in an individual, comprising comparing a measurable characteristic of at least one biomarker between (i) a first biomarker profile obtained from a first biological sample from the individual and (ii) a biomarker profile obtained from biological samples from a reference population, wherein the comparison classifies the individual as belonging to or not belonging to the reference population, wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons, and wherein the comparison determines the status of sepsis in the individual.
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6. A method of determining the status of sepsis in an individual, comprising:
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(a) selecting at least two features from a set of biomarkers in a first biomarker profile generated from a first biological sample of an individual; and
(b) comparing the features to a set of the same biomarkers in a reference biomarker profile generated from biological samples from a reference population, wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population with an accuracy of at least about 60%;
wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one low molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison determines the status of sepsis in the individual.
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7. A method of determining the status of sepsis in an individual, comprising:
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(a) determining an abundance or changes in an abundance of at least two biomarkers in a first biomarker profile obtained from a first biological sample from the individual; and
(b) comparing the abundance or the changes in the abundance of the at least two biomarkers in the individual'"'"'s first biomarker profile to an abundance or changes in an abundance of these biomarkers in a reference biomarker profile obtained from biological samples from a reference population, wherein the comparison is capable of classifying the individual as belonging to or not belonging to the reference population;
wherein said biomarkers in the individual'"'"'s first biomarker profile and said reference biomarker profile have a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison determines the status of sepsis in the individual.
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8. A method of determining the status of sepsis in an individual, comprising determining an abundance or change in an abundance of at least one biomarker from a first biomarker profile obtained from a first biological sample from the individual as compared to an abundance or change in an abundance of the at least one biomarker from biological samples from a (i) SIRS-positive reference population that contracted sepsis and (ii) a SIRS-positive reference population that did not, wherein the biomarkers are selected from the group consisting of the biomarkers listed in any one of TABLES 2-13.
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58. A method of predicting the onset of sepsis in an individual, comprising:
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(a) measuring an aspect of at least two features in a biomarker profile, wherein the biomarker profile comprises at least two biomarkers selected from the set of biomarkers set forth in any one of TABLES 2-13; and
(b) comparing the measured aspect of said at least two features with the value of a corresponding aspect of the same at least two features in a reference population, wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population, and wherein the comparison predicts the onset of sepsis in the individual. - View Dependent Claims (59, 60, 61)
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62. A method of diagnosing SIRS in an individual, comprising:
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(a) obtaining a first biomarker profile from a first biological sample taken from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from a reference population, wherein a single such comparison is capable of classifying the individual as belonging to or not belonging to the reference population;
wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one small molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison diagnoses SIRS in the individual.
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63. A method of diagnosing SIRS in an individual, comprising:
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(a) obtaining a biomarker profile from a biological sample taken at a single point in time from the individual; and
(b) comparing the individual'"'"'s biomarker profile to a reference biomarker profile;
wherein said individual'"'"'s biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one small molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison of the biomarker profiles can diagnose SIRS in the individual with an accuracy of at least about 60%.
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64. A method of diagnosing SIRS in an individual, comprising comparing (i) a first biomarker profile generated from a first biological sample taken from the individual at a single point in time with (ii) a reference biomarker profile generated from a reference population;
- wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one small molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
wherein the comparison comprises applying a decision rule that diagnoses SIRS in the individual.
- wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a measurable aspect of at least one small molecular weight compound having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons; and
Specification