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 or suffering from, or with clinical signs of SIRS (Systemic Inflammatory Response Syndrome) being either infection-negative SIRS or infection-positive SIRS.

The claims defining the invention are as follows: 
     
         1 . A composition comprising a mixture of a DNA polymerase, sample peripheral blood leukocyte cDNA having a cDNA expression profile characteristic of a subject with a clinical sign of systemic inflammatory response syndrome (SIRS), wherein the sample peripheral blood leukocyte cDNA comprises a Olfactomedin 4 (OLFM4) cDNA, and at least one oligonucleotide primer that hybridizes to the OLFM4 cDNA. 
     
     
         2 . The composition of  claim 1 , wherein the sample cDNA expression profile comprises Granulysin (GNLY) cDNA at a lower level than a control cDNA expression profile characteristic of a healthy subject, and each of Toll-like Receptor 5 (TLR5) cDNA, Vanin 1 (VNN1) cDNA, and Matrix Metalloproteinase 9 (MMP9) cDNA at a higher level than the control cDNA expression profile. 
     
     
         3 . The composition of  claim 1 , further comprising a probe that hybridizes to OLFM4 cDNA. 
     
     
         4 . The composition of  claim 1 , further comprising deoxynucleotides. 
     
     
         5 . The composition of  claim 1 , wherein the sample peripheral blood leukocyte cDNA comprises at least one other cDNA selected from the group consisting of a Defensin Alpha 4 (DEFA4) cDNA, Lactotransferrin (LTF) cDNA, Myeloperoxidase (MPO) cDNA, Killer Cell Lectin Like Receptor F1 (KLRF1) cDNA, Vesicle Associated Membrane Protein 2 (VAMP2) cDNA, Killer Cell Lectin Like Receptor D1 (KLRD1) cDNA, Histone Cluster 1 H3 Family Member 3 (HIST1H3J) cDNA, Histone Cluster 1 H3 Family Member A (HIST1H3A) cDNA, PMS2 C-Terminal Like Pseudogene (PMS2CL) cDNA, Beta-1,4-Galactosyltransferase 3 (B4GALT3) cDNA and Immunoglobulin Lambda Variable 1-44 (IGLV1-44), and the composition further comprises at least one oligonucleotide primer that hybridizes to the at least one other cDNA. 
     
     
         6 . The composition of  claim 5 , further comprising a probe that hybridizes to the at least one other cDNA. 
     
     
         7 . The composition of  claim 5 , wherein the sample peripheral blood leukocyte cDNA comprises DEFA4 cDNA, and the composition comprises at least one oligonucleotide primer that hybridizes to the DEFA4 cDNA. 
     
     
         8 . A composition comprising a mixture of a DNA polymerase, sample peripheral blood leukocyte cDNA having a cDNA expression profile characteristic of a subject with a clinical sign of systemic inflammatory response syndrome (SIRS), wherein the sample peripheral blood leukocyte cDNA comprises a Arginase 1 (ARG1) cDNA, and at least one oligonucleotide primer that hybridizes to the ARG1 cDNA. 
     
     
         9 . The composition of  claim 8 , wherein the sample cDNA expression profile comprises Granulysin (GNLY) cDNA at a lower level than a control cDNA expression profile characteristic of a healthy subject, and each of Toll-like Receptor 5 (TLR5) cDNA, Vanin 1 (VNN1) cDNA, and Matrix Metalloproteinase 9 (MMP9) cDNA at a higher level than the control cDNA expression profile. 
     
     
         10 . The composition of  claim 8 , further comprising a probe that hybridizes to ARG1 cDNA. 
     
     
         11 . The composition of  claim 8 , further comprising deoxynucleotides. 
     
     
         12 . The composition of  claim 8 , wherein the sample peripheral blood leukocyte cDNA comprises at least one other cDNA selected from the group consisting of Cluster of Differentiation 177 (CD177), VNN1 cDNA, Tudor Domain Containing 9 (TDRD9), (GPR84) cDNA, 15-Hydroxyprostaglandin Dehydrogenase (HPGD) cDNA, Galectin-Related Protein (HSPC159) cDNA, Folate Receptor Beta (FOLR2) cDNA, Folate Receptor Gamma (FOLR3) cDNA, Lipocalin 2 (LCN2) cDNA, ATP Binding Cassette Subfamily A Member 13 (ABCA13) cDNA, Marker Of Proliferation Ki-67 (MKI67) cDNA, Lactotransferrin (LTF) cDNA, Resistin (RETN) cDNA, Ankyrin Repeat Domain 28 (ANKRD28) cDNA, LHFPL Tetraspan Subfamily Member 6 (LHFP) cDNA, Trace Amine Associated Receptor 1 (TAAR1) cDNA, Defensin Alpha 4 (DEFA4) cDNA, Secreted Protein Acidic And Cysteine Rich (SPARC) cDNA, Joining Chain Of Multimeric IgA And IgM (IGJ) cDNA and High Mobility Group Box 2 (HMGB2) cDNA, and the composition further comprises at least one oligonucleotide primer that hybridizes to the at least one other cDNA. 
     
     
         13 . The composition of  claim 12 , further comprising a probe that hybridizes to the at least one other cDNA. 
     
     
         14 . The composition of  claim 12 , wherein the sample peripheral blood leukocyte cDNA comprises DEFA4 cDNA, and the composition comprises at least one oligonucleotide primer that hybridizes to the DEFA4 cDNA.