US 2019/0194728 A1 · Systemic inflammatory and pathogen biomarkers and uses therefor

Abstract

Disclosed are compositions, methods and apparatus for diagnosing and/or monitoring an infection by a bacterium, virus or protozoan by measurement of pathogen-associated and non-infectious systemic inflammation and optionally in combination with detection of a pathogen specific molecule. The invention can be used for diagnosis, including early diagnosis, ruling-out, ruling-in, monitoring, making treatment decisions, or management of subjects suspected of, or having, systemic inflammation. More particularly, the present disclosure relates to host peripheral blood RNA and protein biomarkers, which are used in combination, and optionally with peripheral blood broad-range pathogen-specific detection assays, that are useful for distinguishing between bacterial, viral, protozoal and non-infectious causes of systemic inflammation.

Claims108

Dependent claims

A method for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS or VaSIRS, the method comprising:

(1) determining a plurality of host response specific biomarker values including a plurality of BaSIRS biomarker values and a plurality of VaSIRS biomarker values, the plurality of BaSIRS biomarker values being indicative of values measured for a corresponding plurality of BaSIRS biomarkers in a sample taken from the subject, the plurality of VaSIRS biomarker values being indicative of values measured for a corresponding plurality of VaSIRS biomarkers in the sample;
(2) determining a plurality of host response specific derived biomarker values including at least one BaSIRS derived biomarker value and at least one VaSIRS derived biomarker value, each derived BaSIRS biomarker value being determined using at least a subset of the plurality of BaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of BaSIRS biomarkers, and each derived VaSIRS biomarker value being determined using at least a subset of the plurality of VaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of VaSIRS biomarkers;
and (3) determining the indicator using the plurality of host response specific derived biomarker values, wherein the at least a subset of BaSIRS biomarkers forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, and wherein the at least a subset of VaSIRS biomarkers forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS.

A method for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS, VaSIRS or PaSIRS, the method comprising:

(1) determining a plurality of host response specific biomarker values including a plurality of BaSIRS biomarker values, a plurality of VaSIRS biomarker values, and a plurality of PaSIRS biomarker values, the plurality of BaSIRS biomarker values being indicative of values measured for a corresponding plurality of BaSIRS biomarkers in a sample taken from the subject, the plurality of VaSIRS biomarker values being indicative of values measured for a corresponding plurality of VaSIRS biomarkers in the sample, the plurality of PaSIRS biomarker values being indicative of values measured for a corresponding plurality of PaSIRS biomarkers in the sample;
(2) determining a plurality of host response specific derived biomarker values including at least one BaSIRS derived biomarker value, at least one VaSIRS derived biomarker value, and at least one PaSIRS derived biomarker value, each derived BaSIRS biomarker value being determined using at least a subset of the plurality of BaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of BaSIRS biomarkers, each derived VaSIRS biomarker value being determined using at least a subset of the plurality of VaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of VaSIRS biomarkers, and each derived PaSIRS biomarker value being determined using at least a subset of the plurality of PaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of PaSIRS biomarkers;
and (3) determining the indicator using the plurality of host response specific derived biomarker values, wherein the at least a subset of BaSIRS biomarkers forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, wherein the at least a subset of VaSIRS biomarkers forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS, and wherein the at least a subset of PaSIRS biomarkers forms a PaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, VaSIRS or InSIRS.

A method for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS, VaSIRS or InSIRS, the method comprising:

(1) determining a plurality of host response specific biomarker values including a plurality of BaSIRS biomarker values, a plurality of VaSIRS biomarker values, and a plurality of InSIRS biomarker values, the plurality of BaSIRS biomarker values being indicative of values measured for a corresponding plurality of BaSIRS biomarkers in a sample taken from the subject, the plurality of VaSIRS biomarker values being indicative of values measured for a corresponding plurality of VaSIRS biomarkers in the sample, the plurality of InSIRS biomarker values being indicative of values measured for a corresponding plurality of InSIRS biomarkers in the sample;
(2) determining a plurality of host response specific derived biomarker values including at least one BaSIRS derived biomarker value, at least one VaSIRS derived biomarker value, and at least one InSIRS derived biomarker value, each derived BaSIRS biomarker value being determined using at least a subset of the plurality of BaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of BaSIRS biomarkers, each derived VaSIRS biomarker value being determined using at least a subset of the plurality of VaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of VaSIRS biomarkers, and each derived InSIRS biomarker value being determined using at least a subset of the plurality of InSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of InSIRS biomarkers;
and (3) determining the indicator using the plurality of host response specific derived biomarker values, wherein the at least a subset of BaSIRS biomarkers forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, wherein the at least a subset of VaSIRS biomarkers forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS, and wherein the at least a subset of InSIRS biomarkers forms an InSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, VaSIRS or PaSIRS.

A method for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS, VaSIRS, PaSIRS or InSIRS, the method comprising:

(1) determining a plurality of host response specific biomarker values including a plurality of BaSIRS biomarker values, a plurality of VaSIRS biomarker values, a plurality of PaSIRS biomarker values, and a plurality of InSIRS biomarker values, the plurality of BaSIRS biomarker values being indicative of values measured for a corresponding plurality of BaSIRS biomarkers in a sample taken from the subject, the plurality of VaSIRS biomarker values being indicative of values measured for a corresponding plurality of VaSIRS biomarkers in the sample, the plurality of PaSIRS biomarker values being indicative of values measured for a corresponding plurality of PaSIRS biomarkers in the sample, the plurality of InSIRS biomarker values being indicative of values measured for a corresponding plurality of InSIRS biomarkers in the sample;
(2) determining a plurality of host response specific derived biomarker values including at least one BaSIRS derived biomarker value, at least one VaSIRS derived biomarker value, at least one PaSIRS derived biomarker value, and at least one InSIRS derived biomarker value, each derived BaSIRS biomarker value being determined using at least a subset of the plurality of BaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of BaSIRS biomarkers, each derived VaSIRS biomarker value being determined using at least a subset of the plurality of VaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of VaSIRS biomarkers, each derived PaSIRS biomarker value being determined using at least a subset of the plurality of PaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of PaSIRS biomarkers, and each derived InSIRS biomarker value being determined using at least a subset of the plurality of InSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of InSIRS biomarkers;
and (3) determining the indicator using the plurality of host response specific derived biomarker values, wherein the at least a subset of BaSIRS biomarkers forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, wherein the at least a subset of VaSIRS biomarkers forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS, wherein the at least a subset of PaSIRS biomarkers forms a PaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, VaSIRS or InSIRS, and wherein the at least a subset of InSIRS biomarkers forms an InSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, VaSIRS or PaSIRS.

An apparatus for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS or VaSIRS. This apparatus generally comprises at least one electronic processing device that:

determines a plurality of host response specific biomarker values including a plurality of BaSIRS biomarker values and a plurality of VaSIRS biomarker values, the plurality of BaSIRS biomarker values being indicative of values measured for a corresponding plurality of BaSIRS biomarkers in a sample taken from the subject, the plurality of VaSIRS biomarker values being indicative of values measured for a corresponding plurality of VaSIRS biomarkers in the sample;
determines a plurality of host response specific derived biomarker values including at least one BaSIRS derived biomarker value and at least one VaSIRS derived biomarker value, each derived BaSIRS biomarker value being determined using at least a subset of the plurality of BaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of BaSIRS biomarkers, and each derived VaSIRS biomarker value being determined using at least a subset of the plurality of VaSIRS biomarker values, and being indicative of a ratio of levels of a corresponding at least a subset of the plurality of VaSIRS biomarkers;
and
determines the indicator using the plurality of host response specific derived biomarker values, wherein the at least a subset of BaSIRS biomarkers forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, and wherein the at least a subset of VaSIRS biomarkers forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS.

1 more element

A composition for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS or VaSIRS, the composition comprising:

(1) a pair of BaSIRS biomarker cDNAs, and for each BaSIRS biomarker cDNA at least one oligonucleotide primer that hybridizes to the BaSIRS biomarker cDNA, and/or at least one oligonucleotide probe that hybridizes to the BaSIRS biomarker cDNA, wherein the at least one oligonucleotide primer and/or the at least one oligonucleotide probe comprises a heterologous label, and (2) a pair of VaSIRS biomarker cDNAs, and for each VaSIRS biomarker cDNA at least one oligonucleotide primer that hybridizes to the VaSIRS biomarker cDNA, and/or at least one oligonucleotide probe that hybridizes to the VaSIRS biomarker cDNA, wherein the at least one oligonucleotide primer and/or the at least one oligonucleotide probe comprises a heterologous label, wherein the pair of BaSIRS biomarker cDNAs forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, wherein the pair of VaSIRS biomarker cDNAs forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS, wherein the BaSIRS derived biomarker combination is selected from the BaSIRS derived biomarker combinations set out in TABLE A, and wherein the VaSIRS derived biomarker combination is selected from the VaSIRS derived biomarker combinations set out in TABLE B.

A kit for determining an indicator used in assessing a likelihood of a subject having a presence, absence or degree of BaSIRS or VaSIRS, the kit comprising:

(1) for each of a pair of BaSIRS biomarker cDNAs at least one oligonucleotide primer and/or at least one oligonucleotide probe that hybridizes to the BaSIRS biomarker cDNA, wherein the at least one oligonucleotide primer and/or the at least one oligonucleotide probe comprises a heterologous label;
and (2) for each of a pair of VaSIRS biomarker cDNA at least one oligonucleotide primer and/or at least one oligonucleotide probe that hybridizes to the VaSIRS biomarker cDNA, wherein the at least one oligonucleotide primer and/or the at least one oligonucleotide probe comprise(s) a heterologous label, wherein the pair of BaSIRS biomarker cDNAs forms a BaSIRS derived biomarker combination which is not a derived biomarker combination for VaSIRS, PaSIRS or InSIRS, wherein the pair of VaSIRS biomarker cDNAs forms a VaSIRS derived biomarker combination which is not a derived biomarker combination for BaSIRS, PaSIRS or InSIRS, wherein the BaSIRS derived biomarker combination is selected from the BaSIRS derived biomarker combinations set out in TABLE A, and wherein the VaSIRS derived biomarker combination is selected from the VaSIRS derived biomarker combinations set out in TABLE B.

Dependencies are inferred from the claim text.

Systemic inflammatory and pathogen biomarkers and uses therefor

Life of this patent

Systemic inflammatory and pathogen biomarkers and uses therefor

Life of this patent

Abstract

Claims108