Application US20150218640

BIOMARKER SIGNATURE METHOD, AND APPARATUS AND KITS THEREFOR
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US20150218640

1. A composition comprising at least one pair of reverse transcribed mRNAs and at least one oligonucleotide primer or probe that hybridizes to an individual one of the reverse transcribed mRNAs, the at least one pair of reverse transcribed mRNAs comprising a first pair and a second pair of reverse transcribed mRNAs, wherein the first pair comprises a PLAC8 reverse transcribed mRNA and a PLA2G7 reverse transcribed mRNA and wherein the second pair comprises a CEACAM4 reverse transcribed mRNA and a LAMP1 reverse transcribed mRNA. (6) (0)

2. The composition according to claim 1, wherein the at least one oligonucleotide primer or probe is hybridized to an individual one of the reverse transcribed mRNAs. (0)

3. The composition according to claim 1, wherein the reverse transcribed mRNAs are derived from components of the immune system. (0)

4. The composition according to claim 1, wherein the reverse transcribed mRNAs are derived from leukocytes. (0)

5. The composition according to claim 1, wherein the reverse transcribed mRNAs are derived from blood cells. (0)

6. The composition according to claim 1, wherein the reverse transcribed mRNAs are derived from peripheral blood cells. (2) (0)

7. The composition according to claim 1, further comprising a labeled reagent for detecting the reverse transcribed mRNAs. (0)

10. A method for differentiating between inSIRS and ipSIRS in a biological subject, the method including: (8) (5)

a) obtaining a sample taken from a biological subject showing a clinical sign of SIRS, the sample including polynucleotide expression products;

b) quantifying polynucleotide expression products within the sample to determine a pair of biomarker values, the pair of biomarker values being selected from the group consisting of: i) a first pair of biomarker values indicative of a concentration of polynucleotide expression products of the PLA2G7 gene and PLAC8 gene;

ii) a second pair of biomarker values indicative of a concentration of polynucleotide expression products of the CEACAM4 gene and LAMP1 gene;

c) determining an indicator indicative of a ratio of concentrations of the polynucleotide expression products using the pair of biomarker values;

d) comparing the indicator to first and second indicator references, the first and second indicator references being indicative of inSIRS and ipSIRS, respectively; and,

e) determining a likelihood of the subject having inSIRS or ipSIRS in accordance with the results of the comparison.

11. The method according to claim 10, wherein the method includes: (2) (3)

a) determining a first derived biomarker value using the first pair of biomarker values;

b) determining a second derived biomarker value using the second pair of biomarker values; and,

c) determining the indicator by combining the first and second derived biomarker values.

12. The method according to claim 11, wherein the method includes combining the derived biomarker values using a combining function, the combining function being at least one of: (0) (11)

a) an additive model;

b) a linear model;

c) a support vector machine;

d) a neural network model;

e) a random forest model;

f) a regression model;

g) a genetic algorithm;

h) an annealing algorithm;

i) a weighted sum;

j) a nearest neighbour model; and,

k) a probabilistic model.

14. The method according to claim 11, wherein the method includes, in at least one electronic processing device: (0) (4)

a) obtaining the pairs of biomarker values;

b) determining the first derived biomarker value;

c) determining the second derived biomarker value; and,

d) determining the indicator by adding the first and second derived biomarker values.

13. The method according to claim 10, wherein the method is performed at least in part using an electronic processing device. (0)

15. The method according to claim 10, wherein the method includes, in at least one processing device, generating a representation of the indicator. (1) (0)

17. The method according to claim 10, wherein the indicator references are based on at least one of: (0) (3)

18. The method according to claim 10, wherein the indicator references are derived from indicators determined for a number of individuals in a reference population. (2) (0)

19. The method according to claim 18, wherein the indicator reference is based on a distribution of indicators determined for a group of a reference population, the group consisting of individuals diagnosed as having the medical condition or lacking the medical condition. (0)

20. The method according to claim 18, wherein the reference population includes at least one of: (0) (8)

a) a plurality of individuals of different sexes;

b) a plurality of individuals of different ethnicities;

c) a plurality of healthy individuals;

d) a plurality of individuals suffering from at least one of inSIRS and ipSIRS;

e) a plurality of individuals lacking at least one of inSIRS and ipSIRS;

f) a plurality of individuals showing clinical signs of at least one of inSIRS and ipSIRS;

g) first and second groups of individuals, each group of individuals suffering from one of inSIRS and ipSIRS; and,

h) first and second groups of individuals, the first group of individuals suffering from at least one of inSIRS and ipSIRS, and the second group lacking one or both of inSIRS and ipSIRS.

21. The method according to claim 10, wherein the likelihood is based on a probability generated using the results of the comparison. (0)

22. The method according to claim 10, wherein the method includes: (0) (2)

23. The method according to claim 10, wherein the method includes: (2) (2)

a) quantifying polynucleotide expression products by: i) amplifying at least some polynucleotide expression products in the sample; and,

ii) determining an amplification amount representing a degree of amplification required to obtain a defined level of each of a pair of polynucleotide expression products; and,

b) determining the indicator by determining a difference between the amplification amounts.

24. The method according to claim 23, wherein the amplification amount is at least one of: (0) (5)

a) a cycle time;

b) a number of cycles;

c) a cycle threshold;

d) an amplification time; and,

e) relative to an amplification amount of another amplified product.

25. The method according to claim 23, wherein the method includes determining: (0) (3)

26. A kit for determining an indicator indicative of the likelihood of the presence or absence of at least one condition selected from the group consisting of inSIRS and ipSIRS, the kit comprising at least one pair of reagents comprising a first pair of reagents and a second pair of reagents, wherein the first pair of reagents comprises (i) a reagent that allows quantification of a polynucleotide expression product of the PLA2G7 gene; and (ii) a reagent that allows quantification of a polynucleotide expression product of the PLAC8 gene, wherein the second pair of reagents comprises: (iii) a reagent that allows quantification of a polynucleotide expression product of the CEACAM4 gene; and (iv) a reagent that allows quantification of a polynucleotide expression product of the LAMP1 gene. (0)

27. A method for inhibiting the development or progression in a subject of at least one condition selected from the group consisting of inSIRS and ipSIRS, the method comprising: exposing the subject to a treatment regimen for treating the at least one condition based on an indicator obtained from an indicator-determining method, wherein the indicator is indicative of the presence of the at least one condition in the subject, the indicator-determining method comprising: (a) determining at least one pair of biomarker values, each biomarker value being a value measured or derived for at least one corresponding immune system biomarker of the biological subject and being at least partially indicative of a concentration of the immune system biomarker in a sample taken from the subject, (b) determining at least one derived biomarker value using the at least one pair of biomarker values, the derived biomarker value being indicative of a ratio of concentrations of the at least one pair of immune system biomarkers; and (c) determining the indicator based on the at least one derived biomarker value, wherein the pair of biomarker values comprises at least one of: (3) (2)

a) a first pair of biomarker values comprising first and second biomarker values corresponding to first and second biomarkers, wherein the first immune system biomarker represents a polynucleotide expression product of the PLA2G7 gene and wherein the second immune system biomarker representing a polynucleotide expression product of the PLAC8 gene, and

b) a second pair of biomarker values comprises third and fourth biomarker values corresponding to third and fourth immune system biomarkers, respectively, wherein the third immune system biomarker represents a polynucleotide expression product of the CEACAM4 gene and wherein the fourth immune system biomarker represents a polynucleotide expression product of the LAMP1 gene.

28. The method according to claim 27, wherein the indicator-determining method comprises: determining the first pair and second pair of biomarker values and determining a first derived biomarker value calculated using the first pair of biomarker values and a second derived biomarker value calculated using the second pair of biomarker values; and determining the indicator based on a combination of the first and second derived biomarker values. (0)

29. The method according to claim 27, comprising: sending the sample taken from the subject to a laboratory at which the indicator is determined. (0)

30. The method according to claim 27, wherein the sample comprises cells obtained from the subject or a nucleic acid sample thereof. (0)

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Application US20150218640

BIOMARKER SIGNATURE METHOD, AND APPARATUS AND KITS THEREFOR

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