Biomarker identification

Abstract

Disclosed are method and apparatus for identifying biomarkers and in particular for identifying biomarkers for use in making clinical assessments, such as early diagnostic, diagnostic, disease stage, disease severity, disease subtype, response to therapy or prognostic assessments. In one particular example, the techniques are applied to allow assessments of patients suffering from, suspected of suffering from, or with clinical signs of SIRS (Systemic Inflammatory Response Syndrome) being either infection-negative SIRS or infection-positive SIRS.

1 . A composition comprising at least one reverse transcribed mRNA selected from a C3AR1 reverse transcribed mRNA and a HLA-DBP1 reverse transcribed mRNA, and at least one oligonucleotide primer or probe that hybridizes to the at least one reverse transcribed mRNA, wherein the at least one reverse transcribed mRNA is from a subject with a clinical sign of SIRS. 
     
     
         2 . The composition according to  claim 1 , wherein the at least one oligonucleotide primer or probe is hybridized to the at least one reverse transcribed mRNA. 
     
     
         3 . The composition according to  claim 1 , wherein the at least one reverse transcribed mRNA is derived from immune cells. 
     
     
         4 . The composition according to  claim 1 , wherein the at least one reverse transcribed mRNA is derived from leukocytes. 
     
     
         5 . The composition according to  claim 1 , wherein the at least one reverse transcribed mRNA is derived from blood cells. 
     
     
         6 . The composition according to  claim 1 , wherein the at least one reverse transcribed mRNA is derived from peripheral blood cells. 
     
     
         7 . The composition according to  claim 1 , further comprising a labeled reagent for detecting the at least one reverse transcribed mRNA. 
     
     
         8 . The composition according to  claim 7 , wherein the labeled reagent is a labeled said at least one oligonucleotide primer or probe. 
     
     
         9 . The composition according to  claim 7 , wherein the labeled reagent is a labeled said at least one reverse transcribed mRNA. 
     
     
         10 . A kit for determining the presence or absence of at least one condition selected from the group consisting of inSIRS and ipSIRS, the kit comprising (i) a reagent that allows quantification of a polynucleotide expression product of the C3AR1 gene; and (ii) a reagent that allows quantification of a polynucleotide expression product of the HLA-DBP1 gene. 
     
     
         11 . A method for treating, preventing or inhibiting the development of inSIRS or ipSIRS in a subject, the method comprising: administering to the subject an effective amount of an agent that treats or ameliorates the symptoms or reverses or inhibits the development of inSIRS or ipSIRS on the basis that the subject has an increased likelihood of having inSIRS or ipSIRS, as determined by a condition-determining method that comprises: (1) providing a correlation of a reference IRS biomarker profile with the presence or absence, or degree of a condition selected from a healthy condition, SIRS, inSIRS or ipSIRS, wherein the reference IRS biomarker profile evaluates at least one IRS biomarker; (2) obtaining an IRS biomarker profile of a sample from the subject, wherein the sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker; and (3) determining a likelihood of the subject having or not having the condition based on the sample IRS biomarker profile and the reference IRS biomarker profile, wherein an individual IRS biomarker is an expression product of an IRS biomarker gene selected from the group consisting of C3AR1 and HLA-DPB1. 
     
     
         12 . The method according to  claim 11 , wherein the condition-determining method determines the likelihood that SIRS or a healthy condition is present or absent in the subject, and wherein the condition-determining method comprises: 1) providing a correlation of a reference IRS biomarker profile with the presence or absence of SIRS or the healthy condition, wherein the reference biomarker profile evaluates at least one IRS biomarker selected from C3AR1 and HLA-DPB1; (2) obtaining a sample IRS biomarker profile from the subject, which evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker, and (3) determining a likelihood of the subject having or not having the healthy condition or SIRS based on the sample IRS biomarker profile and the reference IRS biomarker profile. 
     
     
         13 . The method according to  claim 11 , wherein the condition-determining method determines the likelihood that inSIRS, ipSIRS or a healthy condition is present or absent in the subject, and wherein the condition-determining method comprises: 1) providing a correlation of a reference IRS biomarker profile with the likelihood of having or not having inSIRS, ipSIRS or the healthy condition, wherein the reference biomarker profile evaluates C3AR1; (2) obtaining a sample IRS biomarker profile from the subject, which evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker; and (3) determining a likelihood of the subject having or not having inSIRS, ipSIRS or a healthy condition the condition based on the sample IRS biomarker profile and the reference IRS biomarker profile. 
     
     
         14 . The method according to  claim 11 , wherein the condition-determining method determines the likelihood that inSIRS or ipSIRS is present or absent in the subject, and wherein the condition-determining method comprises: 1) providing a correlation of a reference IRS biomarker profile with the likelihood of having or not having inSIRS or ipSIRS, wherein the reference biomarker profile evaluates C3AR1; (2) obtaining a sample IRS biomarker profile from the subject, which evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker; and (3) determining a likelihood of the subject having or not having inSIRS or ipSIRS based on the sample IRS biomarker profile and the reference IRS biomarker profile. 
     
     
         15 . The method according to  claim 11 , wherein the condition-determining method determines the likelihood that a stage of ipSIRS selected from mild sepsis, severe sepsis and septic shock is present or absent the subject, and wherein the condition-determining method comprises: 1) providing a correlation of a reference IRS biomarker profile with the likelihood of having or not having the stage of ipSIRS, wherein the reference biomarker IRS biomarker profile evaluates HLA-DPB1; (2) obtaining a sample IRS biomarker profile from the subject, which evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker; and (3) determining a likelihood of the subject having or not having the stage of ipSIRS based on the sample IRS biomarker profile and the reference IRS biomarker profile. 
     
     
         16 . The method according to  claim 11 , wherein an individual IRS biomarker is selected from the group consisting of: (a) a polynucleotide expression product comprising a nucleotide sequence that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with the sequence set forth in any one of SEQ ID NO: 8 and 58, or a complement thereof; (b) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:327 and 375; (c) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with at least a portion of the sequence set forth in SEQ ID NO:327 and 375; and (d) a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under high stringency conditions. 
     
     
         17 . The method according to  claim 12 , wherein an individual IRS biomarker is selected from the group consisting of: (a) a polynucleotide expression product comprising a nucleotide sequence that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with the sequence set forth in any one of SEQ ID NO: 8 and 58, or a complement thereof; (b) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:327 and 375; (c) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with at least a portion of the sequence set forth in SEQ ID NO:327 and 375; and (d) a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under high stringency conditions. 
     
     
         18 . The method according to  claim 13 , wherein an individual IRS biomarker is selected from the group consisting of: (a) a polynucleotide expression product comprising a nucleotide sequence that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with the sequence set forth in any one of SEQ ID NO: 8 and 58, or a complement thereof; (b) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:327 and 375; (c) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with at least a portion of the sequence set forth in SEQ ID NO:327 and 375; and (d) a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under high stringency conditions. 
     
     
         19 . The method according to  claim 14 , wherein an individual IRS biomarker is selected from the group consisting of: (a) a polynucleotide expression product comprising a nucleotide sequence that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with the sequence set forth in any one of SEQ ID NO: 8 and 58, or a complement thereof; (b) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:327 and 375; (c) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with at least a portion of the sequence set forth in SEQ ID NO:327 and 375; and (d) a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under high stringency conditions. 
     
     
         20 . The method according to  claim 15 , wherein an individual IRS biomarker is selected from the group consisting of: (a) a polynucleotide expression product comprising a nucleotide sequence that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with the sequence set forth in any one of SEQ ID NO: 8 and 58, or a complement thereof; (b) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NO:327 and 375; (c) a polynucleotide expression product comprising a nucleotide sequence that encodes a polypeptide that shares at least 90% (or at least 91% to at least 99% and all integer percentages in between) sequence identity with at least a portion of the sequence set forth in SEQ ID NO:327 and 375; and (d) a polynucleotide expression product comprising a nucleotide sequence that hybridizes to the sequence of (a), (b), (c) or a complement thereof, under high stringency conditions.