US 12,071,668 B2
Gene expression signatures useful to predict or diagnose sepsis and methods of using the same
Ephraim L. Tsalik, Cary, NC (US); Geoffrey S. Ginsburg, Durham, NC (US); Christopher W. Woods, Durham, NC (US); Ricardo Henao Giraldo, Durham, NC (US); and Rachel A. Myers, Raleigh, NC (US)
Assigned to Duke University, Durham, NC (US); and United States Government as Represented by the Department of Veterans Affairs, Washington, DC (US)
Filed by Duke University, Durham, NC (US); and United States Government as Represented by the Department of Veterans Affairs, Washington, DC (US)
Filed on Feb. 18, 2022, as Appl. No. 17/651,579.
Application 17/651,579 is a continuation of application No. 16/478,202, granted, now 11,286,525, previously published as PCT/US2018/013832, filed on Jan. 16, 2018.
Claims priority of provisional application 62/446,940, filed on Jan. 17, 2017.
Prior Publication US 2022/0251647 A1, Aug. 11, 2022
Int. Cl. C12Q 1/6876 (2018.01)
CPC C12Q 1/6876 (2013.01) [C12Q 2600/118 (2013.01); C12Q 2600/158 (2013.01)] 9 Claims
 
1. A method of treating sepsis in a subject in need thereof comprising administering to said subject an appropriate treatment regimen based on determining whether a subject has sepsis or is at risk of developing sepsis,
wherein the appropriate treatment regimen is selected from the group consisting of: administering an antibiotic, hydration, transfusion of blood products, vasopressors, ventilator assistance, and combinations thereof, and
wherein the determining is carried out by a method comprising:
providing a biological sample of the subject; and
measuring on a platform the mRNA level of each of the PCBP1, TMBIM6, LASP1, KLF2, OS9, APMAP, CD14, NAMPT, NQO2, CDK5RAP2, SIGLEC10, TSC22D3, RCN3, LST1, HBA1, FGR, TYMP, ATG16L2, CEACAM4, PECAM1, HMHA1, APOBEC3A, and P2RX1 genes in the biological sample, and detecting:
i) an increase in expression of three, four or five or more genes selected from the group consisting of: PCBP1, TMBIM6, LASP1, KLF2, OS9, APMAP, CD14, NAMPT, NQO2, and CDK5RAP2; and
ii) a decrease in expression of three, four or five or more genes selected from the group consisting of: SIGLEC10, TSC22D3, RCN3, LST1, HBA1, FGR, TYMP, ATG16L2, CEACAM4, PECAM1, HMHA1, APOBEC3A, and P2RX1;
wherein the increase and decrease in expression is determined by comparing mRNA expression values between the subject and uninfected controls;
wherein said subject is identified as having sepsis or at risk of developing sepsis when said i) increase in expression and said ii) decrease in expression is present; and
wherein said biological sample is a blood sample.