Assay for pre-operative prediction of organ function recovery

Abstract

Gene expression is measured in a sample of peripheral blood mononuclear cells (PBMCs) obtained from a subject and used to predict organ function recovery. A Function Recovery Potential (FRP) score is assigned to a sample that reflects the measured expression level of the genes identified herein in a direction associated with recovery from organ failure. Treatment of the subject with optimal medical management (OMM) and/or palliative care (PC) is advised when the FRP score is lower than the reference value, and referring the subject for treatment with therapies including—but not limited to—mechanical circulatory support (MCS) surgery, heart transplant (HTx) surgery, or other intervention for advanced heart failure is advised when the FRP score is greater than the reference value. A method for developing an FRP scoring algorithm that predicts a subject's ability to recover from medical intervention for organ failure is also described.

1 - 20 . (canceled) 
     
     
         21 . A method for identifying an individual with a high risk of not recovering from a treatment for organ failure, comprising:
 (a) detecting:
 (i) a differential expression of at least one T cell regulation gene; and 
 (ii) a differential expression of at least one additional gene in at least one sample from the individual by comparing expression of at least one T cell regulation gene and expression of at least one additional gene with a reference expression; and 
   (b) identifying the individual with the high risk of not recovering from the treatment for organ failure when the differential expression of the at least one T cell regulation gene and the differential expression of the at least one additional gene are detected.   
     
     
         22 . The method of  claim 21 , wherein the at least one T cell regulation gene comprises ACVR1C or DNM1P46. 
     
     
         23 . The method of  claim 21 , wherein the at least one additional gene comprises a metabolism gene, a catabolic metabolism gene, an immune system development gene, an RNA metabolism gene, an innate immunity gene, an immune process gene, an immunoglobulin gene, a G-protein, a neuromuscular junction (NMJ) gene, a microtubule-associated gene, or an antisense RNA gene. 
     
     
         24 . The method of  claim 23 , wherein the at least one additional gene comprises ACOT11, ADAM21, ADAMTS1, ADAMTS2, ADM2, AFAP1-AS1, AGRN, ALDH1A1, ANKRD22, ASPSCR1, AXL, BATF2, BCORP1, C15orf38, C2orf91, C4orf48, C5orf20, C5orf45, C6orf164, C7orf50, CACNA1A, CATSPER2P1, CBX3P2, CCDC102B, CCDC154, CCDC86, CCR8, CD1E, CD209, CDCA2, CELSR2, CEMP1, CHMP6, CHRNA2, CKAP2L, COMTD1, CRYBB2, CXCL9, DDX3Y, DDX43, DGKK, DLG3, EGR2, EIF1AY, ETV5, FADS3, FAM84B, FITM1, FMO9P, FRMD6, FSD1, FZD4, GBP6, GBP7, GNG11, GP11BB, GP9, GPKOW, GPR63, GZMK, HBEGF, HEXA-AS1, HIF1A-AS2, HMCN1, IGLL3P, IGSF10, INHBB, JAKMIP2, KAL1, KCNA7, KCNH8, KCNJ2-AS1, KDM5D, KIR2DL1, KIR2DL4, KLB, LENG9, LEPREL1, LINC00515, LOC643387, LOC728431, LYL1, MB21D2, MFSD3, MME, MUC20, NAPSA, NAPSB, NEFL, NEGR1, NLRP2, NTSR1, NXF3, ODF3L2, OLFM1, OR7A5, PDZK11P1, PFDN6, PMP22, PPFIA4, PPIAL4G, PRADC1, PRKY, PRRG1, PRSS12, PTGDR2, RANBP17, RBPMS2, RHBDD3, RPL23AP82, RPL7, RPS4Y1, RSG1, SAC3D1, SALL2, SAP25, SEPT5, SEPT5-GP1BB, SERPINE2, SEZ6L, SKA1, SLC22A1, SNAPC2, SNORA26, SNORA3, SNORA33, SNORD16, SPOCD1, SPTBN5, ST6GALNAC1, STYK1, TIMP3, TLR3, TMEM30B, TNIP3, TPRA1, TTTY15, TXLNG2P, USP18, USP9Y, UTS2, UTY, WDR88, XIST, ZFY, ZNF385D, ZNF501, ZNF658, or ZNF702P; 
     
     
         25 . The method of  claim 24 , wherein the at least one additional gene comprises AGRN, ANKRD22, BATF2, BCORP1, FRMD6, HEXA-AS1, KIR2DL4, NAPSA, RHBDD3, SAP25, or TIMP3. 
     
     
         26 . The method of  claim 21 , wherein the treatment comprises interventional treatment, surgical treatment, or a combination thereof. 
     
     
         27 . The method of  claim 21 , wherein the at least one sample comprises blood, urine, sputum, hair, or skin. 
     
     
         28 . The method of  claim 21 , wherein the reference expression comprises gene expression obtained from a subject who has recovered from a treatment for organ failure or a healthy subject. 
     
     
         29 . The method of  claim 21 , wherein the individual identified with the high risk is recommended for palliative treatment or optimal medical management. 
     
     
         30 . The method of  claim 21 , wherein the individual not identified with the high risk is recommended for an interventional treatment, a surgical treatment, or a combination thereof. 
     
     
         31 . The method of  claim 30 , wherein the interventional treatment or the surgical treatment comprises mechanical circulatory support (MCS) surgery, heart transplant (HTx) surgery, coronary artery bypass graft (CABG) surgery, percutaneous coronary interventions (PCI), aortic valve replacement (AVR) surgery, mitral valve replacement (MVR) surgery, trans-catheter aortic valve replacement (TAVR), transcatheter mitral clip, ventricular tachycardia ablation, stellate gangliectomy, liver surgery, liver transplant, kidney surgery, kidney transplant, lung surgery, lung transplant or immune system failure management with immunomodulators. 
     
     
         32 . A system for identifying an individual with a high risk of not recovering from a treatment for organ failure, comprising:
 (a) a digital processing device comprising an operating system configured to perform executable instructions and a memory;   (b) a computer program including instructions executable by the digital processing device, the computer program is configured to:
 (i) determine a differential expression of at least one T cell regulation gene and a differential expression of at least one additional gene in at least one sample from the individual by comparing expression of at least one T cell regulation gene and expression of at least one additional gene with a reference expression; and 
 (ii) identifying the individual with the high risk of not recovering from a treatment for organ failure when the differential expression of the at least one T cell regulation gene and the differential expression of the at least one additional gene are detected. 
   
     
     
         33 . The system of  claim 32 , wherein the at least one T cell regulation gene comprises ACVR1C or DNM1P46. 
     
     
         34 . The system of  claim 32 , wherein the at least one additional gene comprises a metabolism gene, a catabolic metabolism gene, an immune system development gene, an RNA metabolism gene, an innate immunity gene, and immune process gene, an immunoglobulin gene, a G-protein, a neuromuscular junction (NMJ) gene, a microtubule-associated gene, or an antisense RNA gene. 
     
     
         35 . The system of  claim 34 , wherein the at least one additional gene comprises ACOT11, ADAM21, ADAMTS1, ADAMTS2, ADM2, AFAP1-AS1, AGRN, ALDH1A1, ANKRD22, ASPSCR1, AXL, BATF2, BCORP1, C15orf38, C2orf91, C4orf48, C5orf20, C5orf45, C6orf164, C7orf50, CACNA1A, CATSPER2P1, CBX3P2, CCDC102B, CCDC154, CCDC86, CCR8, CD1E, CD209, CDCA2, CELSR2, CEMP1, CHMP6, CHRNA2, CKAP2L, COMTD1, CRYBB2, CXCL9, DDX3Y, DDX43, DGKK, DLG3, EGR2, EIF1AY, ETV5, FADS3, FAM84B, FITM1, FMO9P, FRMD6, FSD1, FZD4, GBP6, GBP7, GNG11, GP11BE, GP9, GPKOW, GPR63, GZMK, HBEGF, HEXA-AS1, HIF1A-AS2, HMCN1, IGLL3P, IGSF10, INHBB, JAKMIP2, KAL1, KCNA7, KCNH8, KCNJ2-AS1, KDM5D, KIR2DL1, KIR2DL4, KLB, LENG9, LEPREL1, LINC00515, LOC643387, LOC728431, LYL1, MB21D2, MFSD3, MME, MUC20, NAPSA, NAPSB, NEFL, NEGR1, NLRP2, NTSR1, NXF3, ODF3L2, OLFM1, OR7A5, PDZK11P1, PFDN6, PMP22, PPFIA4, PPIAL4G, PRADC1, PRKY, PRRG1, PRSS12, PTGDR2, RANBP17, RBPMS2, RHBDD3, RPL23AP82, RPL7, RPS4Y1, RSG1, SAC3D1, SALL2, SAP25, SEPT5, SEPT5-GP1BB, SERPINE2, SEZ6L, SKA1, SLC22A1, SNAPC2, SNORA26, SNORA3, SNORA33, SNORD16, SPOCD1, SPTBN5, ST6GALNAC1, STYK1, TIMP3, TLR3, TMEM30B, TNIP3, TPRA1, TTTY15, TXLNG2P, USP18, USP9Y, UTS2, UTY, WDR88, XIST, ZFY, ZNF385D, ZNF501, ZNF658, or ZNF702P. 
     
     
         36 . The system of  claim 35 , wherein the at least one additional gene comprises AGRN, ANKRD22, BATF2, BCORP1, FRMD6, HEXA-AS1, KIR2DL4, NAPSA, RHBDD3, SAP25, or TIMP3. 
     
     
         37 . The system of  claim 32 , wherein the treatment comprises interventional treatment, surgical treatment, or a combination thereof. 
     
     
         38 . The system of  claim 32 , wherein the individual identified with the high risk is recommended for palliative treatment or optimal medical management. 
     
     
         39 . The system of  claim 32 , wherein the individual not identified with the high risk is recommended for an interventional treatment, a surgical treatment, or a combination thereof. 
     
     
         40 . The system of  claim 32  further comprises a treatment determination module configured to determine a treatment based on identifying the individual with or without the high risk, said treatment comprises a palliative treatment, optimal medical management, mechanical circulatory support (MCS) surgery, heart transplant (HTx) surgery, coronary artery bypass graft (CABG) surgery, percutaneous coronary interventions (PCI), aortic valve replacement (AVR) surgery, mitral valve replacement (MVR) surgery, trans-catheter aortic valve replacement (TAVR), transcatheter mitral clip, ventricular tachycardia ablation, stellate gangliectomy, liver surgery, liver transplant, kidney surgery, kidney transplant, lung surgery, lung transplant or immune system failure management with immunomodulators.