Metabolic signature for prediction of mucosal inflammation and microbial composition
AssigneeImperial College Innovations Limited
InventorsDavid A. MACINTYRE, Pamela PRUSKI, Gonçalo DOS SANTOS CORREIA, Holly LEWIS, Phillip R. BENNETT, Zoltan TAKATS
Life of this patent
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Abstract
The present invention relates to methods for obtaining a metabolic signature in a subject, said method being applicable for a range of purposes, including diagnosing disease, monitoring disease progression and/or determining a suitable treatment plan.
Claims24
A method comprising the steps of:
- (i) analysing a mucosal sample obtained from a subject to identify the presence and/or level of one or more biomarkers, or any combination of the biomarkers, wherein the biomarkers are selected from a panel of biomarkers, wherein the panel of biomarkers comprises amino-aminohexyl-diaminomethylideneamino-pentanamide, aminonaphthalene, amino-sulfanylheptenyl-amino-oxooctadecanoic acid, arachidic acid (C20:0), arginine, asparagine, aspartic acid, butynoate, cadaverine, carboxysulfanyl-pentanedioic acid, Cer(d24:1/18:1), cerotic acid (C26:0), DG(36:3), dihydroxy-octadecadienoic acid, dimethoxyphenyl-hexadecylcarbamothioyl-propenamide, docosanoic acid (C22:0), docosanylsulfanylbutanoic acid, docosenoic acid (C22:1), eicosadienoic acid (C20:2), eicosanoic acid, ethyl-hexadecylcarbamothioylamino-oxobutanoate, galabiosylceramide (d18:1/16:0), galbeta-Cer(d40:1), glutamate, glutamine, glutamyl-leucine, glycyl-phenylalanine, heptadecylenic acid (C17:1), heptadecyl-hydroxyimidazole, hexadecenylsuccinic acid, histamine, HODE, hydroxycaproic acid, hydroxyglutaric acid, hydroxyvaleric acid, lactoylcysteine, leucine, leucyl-alanine, leucyl-glutamine, leucyl-glycyl-glycine, leucyl-serine, leucyl-threonine, lignoceric acid (C24:0), linoleic acid (C18:2), linolenic acid (C18:3), lysine, lyso-PE(16:1), lyso-PE(18:1), lyso-PE(18:2), lyso-PE(20:4), lyso-PE(O-16:0), lyso-PG(16:0), lyso-PS(18:0), maltotriose, methoxymethyl methyl-glucopyranosiduronate, methyl-hexadecylcarbamothioylamino-oxobutanoate, N2-acetyl-ornithine, N-acetylcadaverine, N-acetylputrescine, nervonic acid (C24:1), nonadecanoic acid (C19:0), nonadecenoic acid (C19:1), N-palmitoyl glutamine, N-palmitoyl methionine, N-palmitoyl-cysteine, octadecanoyloxamide, octadecanyloxy-propoxy-thiazolyl-propanamide, octadecenylamino-sulfanylpropanoic acid, octadecyl-oxy-octadecanoic acid (SAHSA), oleic acid (C18:1), oxo-octadecadienoic acid, oxoproline, oxosulfanyl-oxazolidinyl-octadecanamide, oxypurinol, PC(O-14:1/18:2), pentacosanoic acid (C25:0), PG(18:1/18:2), phenyl sulfoxide, phenylalanine, phenylethylamine, phenyllactic acid, phosphatidyl glycerol, phytenic acid (C20:1), PI(20:4/18:0), propyl-hexadecylcarbamothioylamino-oxobutanoate, PS(16:0/18:1), PS(18:0/18:1), putrescine, pyridinamine, pyrrolidinecarboxaldehyde, stearic acid (18:0), styrene, succinic acid, thiomalic acid, tolualdehyde, tricosanoic acid (C23:0), tyramine, vaccenyl carnitine, valyl-alanine, valyl-glutamine, valyl-phenylalanine, valyl-serine, vinylaniline, and ximenic acid (C26:1);
- (ii) forming a metabolic profile, wherein said metabolic profile is formed from data showing the presence and/or level of the biomarkers identified in step (i);
- (iii) using a predictive multivariate statistical model and/or a machine learning model pre-trained with metabolic and immuno-profiling datasets obtained from a reference population to predict the subject's mucosal inflammatory state at a mucosal membrane and/or level of immune activation at a mucosal membrane;
- and
- wherein the method further comprises the step of associating the metabolic profile of step ii) with metataxonomic data from a reference population to obtain the microbial composition of the mucosal sample.
(canceled).
The method of claim 12, wherein the biomarkers are selected from a panel of biomarkers comprising amino-aminohexyl-diaminomethylideneamino-pentanamide, aminonaphthalene, arachidic acid (C20:0), arginine, asparagine, aspartic acid, butynoate, cadaverine, carboxysulfanyl-pentanedioic acid, cerotic acid (C26:0), DG(36:3), dihydroxy-octadecadienoic acid, docosanylsulfanylbutanoic acid, eicosadienoic acid (C20:2), eicosanoic acid, glutamate, glutamine, glutamyl-leucine, glycyl-phenylalanine, heptadecylenic acid (C17:1), histamine, HODE, hydroxycaproic acid, hydroxyglutaric acid, hydroxyvaleric acid, leucine, leucyl-alanine, leucyl-glutamine, leucyl-glycyl-glycine, leucyl-serine, leucyl-threonine, lignoceric acid (C24:0), linoleic acid (C18:2), linolenic acid (C18:3), lysine, lyso-PE(16:1), lyso-PE(18:1), lyso-PE(18:2), lyso-PE(20:4), lyso-PE(O-16:0), lyso-PG(16:0), lyso-PS(18:0), maltotriose, methoxymethyl methyl-glucopyranosiduronate, N2-acetyl-ornithine, N-acetylcadaverine, N-acetylputrescine, nervonic acid (C24:1), nonadecanoic acid (C19:0), nonadecenoic acid (C19:1), N-palmitoyl methionine, N-palmitoyl-cysteine, octadecanyloxy-propoxy-thiazolyl-propanamide, octadecenylamino-sulfanylpropanoic acid, octadecyl-oxy-octadecanoic acid (SAHSA), oleic acid (C18:1), oxo-octadecadienoic acid, oxoproline, oxypurinol, PC(O-14:1/18:2), pentacosanoic acid (C25:0), PG(18:1/18:2), phenyl sulfoxide, phenylalanine, phenylethylamine, phenyllactic acid, phosphatidyl glycerol, propyl-hexadecylcarbamothioylamino-oxobutanoate, PS(16:0/18:1), PS(18:0/18:1), putrescine, pyridinamine, pyrrolidinecarboxaldehyde, stearic acid (18:0), styrene, succinic acid, thiomalic acid, tolualdehyde, tricosanoic acid (C23:0), tyramine, vaccenyl carnitine, valyl-alanine, valyl-glutamine, valyl-phenylalanine, valyl-serine, vinylaniline, and ximenic acid (C26:1), or any combinations thereof.
-5. (canceled).
-17. (canceled).
(canceled).
A method of treating a vaginal infection in a subject, said method comprising the steps of:
- (i) analysing a mucosal sample obtained from the subject to identify the presence or level of one or more biomarkers, or any combination of biomarkers, wherein the biomarkers are selected from a panel of biomarkers, wherein the panel of biomarkers comprises amino-aminohexyl-diaminomethylideneamino-pentanamide, aminonaphthalene, amino-sulfanylheptenyl-amino-oxooctadecanoic acid, arachidic acid (C20:0), arginine, asparagine, aspartic acid, butynoate, cadaverine, carboxysulfanyl-pentanedioic acid, Cer(d24:1/18:1), cerotic acid (C26:0), DG(36:3), dihydroxy-octadecadienoic acid, dimethoxyphenyl-hexadecylcarbamothioyl-propenamide, docosanoic acid (C22:0), docosanylsulfanylbutanoic acid, docosenoic acid (C22:1), eicosadienoic acid (C20:2), eicosanoic acid, ethyl-hexadecylcarbamothioylamino-oxobutanoate, galabiosylceramide (d18:1/16:0), galbeta-Cer(d40:1), glutamate, glutamine, glutamyl-leucine, glycyl-phenylalanine, heptadecylenic acid (C17:1), heptadecyl-hydroxyimidazole, hexadecenylsuccinic acid, histamine, HODE, hydroxycaproic acid, hydroxyglutaric acid, hydroxyvaleric acid, lactoylcysteine, leucine, leucyl-alanine, leucyl-glutamine, leucyl-glycyl-glycine, leucyl-serine, leucyl-threonine, lignoceric acid (C24:0), linoleic acid (C18:2), linolenic acid (C18:3), lysine, lyso-PE(16:1), lyso-PE(18:1), lyso-PE(18:2), lyso-PE(20:4), lyso-PE(O-16:0), lyso-PG(16:0), lyso-PS(18:0), maltotriose, methoxymethyl methyl-glucopyranosiduronate, methyl-hexadecylcarbamothioylamino-oxobutanoate, N2-acetyl-ornithine, N-acetylcadaverine, N-acetylputrescine, nervonic acid (C24:1), nonadecanoic acid (C19:0), nonadecenoic acid (C19:1), N-palmitoyl glutamine, N-palmitoyl methionine, N-palmitoyl-cysteine, octadecanoyloxamide, octadecanyloxy-propoxy-thiazolyl-propanamide, octadecenylamino-sulfanylpropanoic acid, octadecyl-oxy-octadecanoic acid (SAHSA), oleic acid (C18:1), oxo-octadecadienoic acid, oxoproline, oxosulfanyl-oxazolidinyl-octadecanamide, oxypurinol, PC(O-14:1/18:2), pentacosanoic acid (C25:0), PG(18:1/18:2), phenyl sulfoxide, phenylalanine, phenylethylamine, phenyllactic acid, phosphatidyl glycerol, phytenic acid (C20:1), PI(20:4/18:0), propyl-hexadecylcarbamothioylamino-oxobutanoate, PS(16:0/18:1), PS(18:0/18:1), putrescine, pyridinamine, pyrrolidinecarboxaldehyde, stearic acid (18:0), styrene, succinic acid, thiomalic acid, tolualdehyde, tricosanoic acid (C23:0), tyramine, vaccenyl carnitine, valyl-alanine, valyl-glutamine, valyl-phenylalanine, valyl-serine, vinylaniline, and ximenic acid (C26:1);
- (ii) forming a metabolic profile, wherein said metabolic profile is formed from data showing the presence or level of the biomarkers identified in step (i);
- (iii) using a predictive multivariate statistical model or a machine learning model pre-trained with metabolic and immuno-profiling datasets obtained from a reference population to predict the subject's mucosal inflammatory state or level of mucosal immune activation;
- and
- wherein the method further comprises the step of associating the metabolic profile of step ii) with metataxonomic data from a reference population to obtain the microbial composition of the mucosal sample, wherein when the subject's mucosal inflammatory state, level of mucosal immune activation or microbial composition are indicative of a vaginal infection, the subject is administered an anti-inflammatory agent, an antibiotic, a live biotherapeutic, a prebiotic, a probiotic, progesterone (P4) or undergoes a cervical cerclage procedure.
A method of preventing pre-term birth in a subject, said method comprising the steps of:
- (i) analysing a mucosal sample obtained from the subject to identify the presence and/or level of one or more biomarkers, or any combination of biomarkers, wherein the biomarkers are selected from a panel of biomarkers, wherein the panel of biomarkers comprises amino-aminohexyl-diaminomethylideneamino-pentanamide, aminonaphthalene, amino-sulfanylheptenyl-amino-oxooctadecanoic acid, arachidic acid (C20:0), arginine, asparagine, aspartic acid, butynoate, cadaverine, carboxysulfanyl-pentanedioic acid, Cer(d24:1/18:1), cerotic acid (C26:0), DG(36:3), dihydroxy-octadecadienoic acid, dimethoxyphenyl-hexadecylcarbamothioyl-propenamide, docosanoic acid (C22:0), docosanylsulfanylbutanoic acid, docosenoic acid (C22:1), eicosadienoic acid (C20:2), eicosanoic acid, ethyl-hexadecylcarbamothioylamino-oxobutanoate, galabiosylceramide (d18:1/16:0), galbeta-Cer (d40:1), glutamate, glutamine, glutamyl-leucine, glycyl-phenylalanine, heptadecylenic acid (C17:1), heptadecyl-hydroxyimidazole, hexadecenylsuccinic acid, histamine, HODE, hydroxycaproic acid, hydroxyglutaric acid, hydroxyvaleric acid, lactoylcysteine, leucine, leucyl-alanine, leucyl-glutamine, leucyl-glycyl-glycine, leucyl-serine, leucyl-threonine, lignoceric acid (C24:0), linoleic acid (C18:2), linolenic acid (C18:3), lysine, lyso-PE(16:1), lyso-PE(18:1), lyso-PE(18:2), lyso-PE(20:4), lyso-PE(O-16:0), lyso-PG(16:0), lyso-PS(18:0), maltotriose, methoxymethyl methyl-glucopyranosiduronate, methyl-hexadecylcarbamothioylamino-oxobutanoate, N2-acetyl-ornithine, N-acetylcadaverine, N-acetylputrescine, nervonic acid (C24:1), nonadecanoic acid (C19:0), nonadecenoic acid (C19:1), N-palmitoyl glutamine, N-palmitoyl methionine, N-palmitoyl-cysteine, octadecanoyloxamide, octadecanyloxy-propoxy-thiazolyl-propanamide, octadecenylamino-sulfanylpropanoic acid, octadecyl-oxy-octadecanoic acid (SAHSA), oleic acid (C18:1), oxo-octadecadienoic acid, oxoproline, oxosulfanyl-oxazolidinyl-octadecanamide, oxypurinol, PC(O-14:1/18:2), pentacosanoic acid (C25:0), PG(18:1/18:2), phenyl sulfoxide, phenylalanine, phenylethylamine, phenyllactic acid, phosphatidyl glycerol, phytenic acid (C20:1), PI(20:4/18:0), propyl-hexadecylcarbamothioylamino-oxobutanoate, PS(16:0/18:1), PS(18:0/18:1), putrescine, pyridinamine, pyrrolidinecarboxaldehyde, stearic acid (18:0), styrene, succinic acid, thiomalic acid, tolualdehyde, tricosanoic acid (C23:0), tyramine, vaccenyl carnitine, valyl-alanine, valyl-glutamine, valyl-phenylalanine, valyl-serine, vinylaniline, and ximenic acid (C26:1);
- (ii) forming a metabolic profile, wherein said metabolic profile is formed from data showing the presence or level of the biomarkers identified in step (i):
- (iii) using a predictive multivariate statistical model or a machine learning model pre-trained with metabolic and immuno-profiling datasets obtained from a reference population to predict the subject's mucosal inflammatory state and/or level of mucosal immune activation;
- and
- wherein the method further comprises the step of associating the metabolic profile of step ii) with metataxonomic data from a reference population to obtain the microbial composition of the mucosal sample, wherein when the subject's mucosal inflammatory state, level of mucosal immune activation or microbial composition are indicative of pre-term birth, the subject is administered a preventative therapy or undergoes a preventative procedure.
Dependencies are inferred from the claim text.