Use of mass spectrometry to detect sepsis

• US 20080050829A1
• Filed: 12/28/2006
• Published: 02/28/2008
• Est. Priority Date: 11/12/2002
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Gentle, Thomas, Goldenbaum, Paul, Towns, Michael, Bachur, Nicholas, Garrett, James, Nadeau, James, Rosenstein, Robert, Tice, Gregory, Shi, Song, Shen, Zhouxin, Moore, Richard, Siuzdak, Gary, Ivey, Richard, Copertino, Donald, Want, Elizabeth
• Granted Patent: US 7,632,685 B2
• Time in Patent Office: Days
• US Class Current: 436/63
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Mass spectrometry techniques for determining the status of sepsis in an individual are provided. A biomarker profile resolved from a biological sample, taken from the individual, using a mass spectrometry technique is compared to a reference biomarker profile. A single such comparison classifies the individual as belonging to or not belonging to a reference population. The individual'"'"'s biomarker profile and the reference biomarker profile comprise a plurality of ions each having a mass-to-charge ratio of about 100 Daltons to about 1000 Daltons. The plurality of ions can be detected by electrospray ionization mass spectrometry in positive mode. The comparison uses a decision rule, such as a classification tree, that determines the status of sepsis in the individual without requiring knowledge of the identity of the biomarkers in the biomarker profile from the individual and without requiring knowledge of the identity of the biomarkers in the reference biomarker profile.

Claims

1. A method of determining the status of sepsis in an individual using mass spectrometry, comprising:

comparing (i) a first biomarker profile resolved from a first biological sample, taken from the individual, using a mass spectrometry technique and (ii) a reference biomarker profile;

wherein a single such comparison classifies the individual as belonging to or not belonging to a reference population;

wherein said individual'"'"'s first biomarker profile and said reference biomarker profile comprise a plurality of ions each 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.

2. The method of claim 1 wherein the comparing comprises applying a decision rule that determines the status of sepsis in the individual.

3. The method of claim 1 wherein the reference biomarker profile is 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 after about 0-36 hours, a SIRS-positive reference population confirmed as having sepsis after about 36-60 hours, and a SIRS-positive reference population confirmed as having sepsis after about 60-84 hours.

4. The method of claim 1 wherein the reference biomarker profile is resolved by mass spectrometry from samples obtained from biological samples from a (i) SIRS-positive reference population that contracted sepsis and (ii) a SIRS-positive reference population that did not contract sepsis.

5. The method claim 1, wherein the first biological sample is selected from the group consisting of blood, saliva, serum, plasma, urine, stool, cerebral spinal fluid, cells, a cellular extract, a tissue sample, and a tissue biopsy.

6. The method of claim 1, further comprising repeating the method at least once, wherein a separate biomarker profile is obtained from the individual from a separate biological sample taken each time the method is repeated.

7. The method of claim 6, wherein said separate biological sample is taken from the individual at 24 hour intervals.

8. The method of claim 1, wherein the determining the status of sepsis in the individual comprises predicting the onset of sepsis in the individual.

9. The method of claim 8, wherein the onset of sepsis is predicted at least about 24 hours prior to the determination of sepsis in the individual by way of clinical criteria.

10. The method of claim 8, wherein the onset of sepsis is predicted at least about 48 hours prior to the determination of sepsis in the individual by way of clinical criteria.

11. The method of claim 8, wherein the onset of sepsis is predicted at least about 96 hours prior to the determination of sepsis in the individual by way of clinical criteria.

12. The method of claim 1, wherein the determining the status of sepsis in the individual comprises determining the progression of sepsis in the individual.

13. The method of claim 1, wherein the determining the status of sepsis in the individual comprises diagnosing sepsis in the individual.

14. The method of claim 1, wherein the comparing step comprises applying a decision rule.

15. The method of claim 14, wherein applying the decision rule comprises using a data analysis algorithm.

16. The method of claim 15, wherein the data analysis algorithm is a classification tree.

17. The method of claim 15, wherein the data analysis algorithm is nonparametric.

18. The method of claim 17, wherein the nonparametric algorithm is a Wilcoxon Signed Rank Test.

19. The method of claim 15, wherein the data analysis algorithm is a multiple additive regression tree.

20. The method of claim 15, wherein the data analysis algorithm is a logistic regression.