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 at a single point in time; and
(b) comparing said individual'"'"'s first biomarker profile to a reference biomarker profile, wherein the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid; and
wherein said comparison determines the status of sepsis in the individual with an accuracy of at least about 60%.
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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 using a molecular diagnostics approach, involving 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.
95 Citations
70 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 at a single point in time; and
(b) comparing said individual'"'"'s first biomarker profile to a reference biomarker profile, wherein the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid; and
wherein said comparison determines the status of sepsis in the individual with an accuracy of at least about 60%. - View Dependent Claims (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, 58)
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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 first biological sample from the individual; and
(b) comparing the individual'"'"'s first biomarker profile to a reference biomarker profile obtained from a reference population, wherein the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, wherein the comparison is capable of classifying the individual as belonging to or not belonging to the reference population, and wherein the comparison determines the status of sepsis in the individual.
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3. 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 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 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 the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, wherein the comparison is capable of classifying the individual as belonging to or not belonging to the reference population, and wherein the comparison 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) comparing a measurable characteristic of at least two host response nucleic acid biomarkers 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; and
(b) classifying the individual as belonging to or not belonging to the reference population, wherein the comparison determines the status of sepsis in the individual. - View Dependent Claims (9)
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5. 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 host response nucleic acid biomarkers in a first biomarker profile generated from a first biological sample of the individual; and
(b) comparing the at least two features to a set of the same host response nucleic acid biomarkers in a biomarker profile generated 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 with an accuracy of at least about 60%, 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) determining an abundance or a change in an abundance of at least two host response nucleic acid biomarkers contained in a first biomarker profile obtained from a first biological sample of the individual; and
(b) comparing the abundance or the change in the abundance to an abundance or change in an abundance of said at least two host response nucleic acid biomarkers contained in 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; 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 determining changes in abundance of at least two host response nucleic acid biomarkers contained in a first biomarker profile obtained from a first biological sample from the individual compared to changes in abundance of said at least two host response nucleic acid biomarkers contained in biological samples from (i) a reference population that contracted sepsis and (ii) a reference population with SIRS, wherein the at least two host response nucleic acid biomarkers are selected from the group of host response nucleic acids set forth in any one of TABLES 2-10.
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8. A method of determining the status of sepsis in an individual, comprising determining an abundance of at least two host response nucleic acid biomarkers contained in a first biomarker profile obtained from a first biological sample from the individual compared to an abundance of said at least two host response nucleic acid biomarkers contained in biological samples from (i) a reference population that contracted sepsis and (ii) a reference population with SIRS, wherein the at least two host response nucleic acid biomarkers are selected from the group of host response nucleic acids set forth in any one of TABLES 2-10.
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59. 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 group of host response nucleic acid biomarkers set forth in any one of TABLES 2-10; 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 (60, 61, 62)
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63. 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 the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, 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 diagnoses SIRS in the individual.
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64. A method of diagnosing SIRS in an individual, comprising:
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(a) obtaining a biomarker profile at a single point in time from the individual; and
(b) comparing the individual'"'"'s biomarker profile to a reference biomarker profile, wherein the individual'"'"'s biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, 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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65. A method of diagnosing SIRS in an individual, comprising comparing (i) a first biomarker profile generated from a biological sample taken from the individual at a single point in time with (ii) a reference biomarker profile generated from a reference population, wherein the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, and wherein the comparison comprises applying a decision rule that determines the status of SIRS in the individual.
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66. 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 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, and 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 the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, 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 diagnoses SIRS in the individual.
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67. A method of diagnosing SIRS 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 the individual'"'"'s first biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, and wherein the comparison diagnoses SIRS in the individual.
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68. A method of diagnosing SIRS in an individual, comprising:
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(a) selecting at least two features from a set of biomarkers in a biomarker profile generated from a first biological sample from an individual; and
(b) comparing the features to a set of the same biomarkers in a 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 the individual'"'"'s biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, and wherein the comparison diagnoses SIRS in the individual.
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69. A method of diagnosing SIRS in an individual, comprising:
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(a) determining an abundance or change in an abundance of at least two biomarkers contained in a first biological sample of an individual; and
(b) comparing the abundance or change in an abundance of the biomarkers in the individual'"'"'s biological sample to an abundance or change in an abundance of these biomarkers in 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 the individual'"'"'s biomarker profile and the reference biomarker profile comprise features that are measurable characteristics of a host response nucleic acid, and wherein the comparison diagnoses SIRS in the individual.
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70. A method of diagnosing SIRS in an individual, comprising determining the abundance or a change in abundance of at least one biomarker obtained from a biological sample from the individual as compared to an abundance or change in an abundance of the at least one biomarker obtained from biological samples from a normal reference population, wherein the biomarkers are selected from the group consisting of the host response nucleic acids listed in any one of TABLES 2-10.
Specification