Nasopharyngeal protein biomarkers of acute respiratory virus infection and methods of using same
AssigneeDuke University
InventorsThomas W. Burke, Ricardo Henao Giraldo, Erik Soderblom, Joseph Lucas, Christopher W. Woods, Geoffrey S. Ginsburg
Life of this patent
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Abstract
The present disclosure provides methods for determining the presence or absence of and/or the etiology of an acute respiratory viral infection in a subject, as well as methods of treating the subject based on the determination, by measuring on a platform the expression levels of a pre-defined set of gene products.
Claims41
A method for making an acute respiratory viral (ARV) illness classifier for a platform, said method comprising:
- (a) obtaining biological samples from a plurality of subjects known to be suffering from an ARV illness;
- (b) measuring on said platform the expression levels of a plurality of pre-defined gene products in each of said biological samples from step (a);
- (c) normalizing the gene product expression levels obtained in step (b) to generate normalized expression values;
- and
- (d) generating an ARV illness classifier for the platform based upon said normalized gene product expression values, to thereby make the ARV illness classifier for the platform.
A method for determining the presence of a respiratory virus in a subject or for determining the viral etiology of an acute respiratory viral (ARV) illness in a subject suffering therefrom, comprising:
- (a) obtaining a biological sample from the subject;
- (b) measuring on a platform expression levels of a pre-defined set of gene products in said biological sample;
- (c) normalizing the gene product expression levels to generate normalized expression values;
- (d) entering the normalized gene product expression values into one or more acute respiratory virus (ARV) illness classifiers, said classifier(s) comprising pre-defined weighting values for each of the gene products of the pre-determined set of proteins and/or peptides for the platform, optionally wherein said classifier(s) are retrieved from one or more databases;
- and
- (e) calculating a presence or an etiology probability for one or more of the ARV illness based upon said normalized expression values and said classifier(s), and optionally determining a threshold for the determination of ARV illness,
- to thereby determine the presence of a respiratory virus in the subject or the viral etiology of an ARV illness in the subject.
12-13. (canceled)
A method for determining whether a subject is at risk of developing an ARV illness, or for determining the presence of a latent or subclinical respiratory viral infection in a subject exhibiting no symptoms, comprising:
- (a) obtaining a biological sample from the subject;
- (b) measuring on a platform expression levels of a pre-defined set of gene products in said biological sample;
- (c) normalizing the gene product expression levels to generate normalized expression values;
- (d) entering the normalized gene product expression values into one or more acute respiratory virus illness classifiers, said classifier(s) comprising pre-defined weighting values for each of the gene products of the pre-determined set of proteins and/or peptides for the platform, optionally wherein said classifier(s) are retrieved from one or more databases;
- and
- (e) calculating a risk probability or a probability for one or more of an ARV illness based upon said normalized expression values and said classifier(s), and optionally determining a threshold for the determination of ARV illness, to thereby determine whether the subject is a risk of developing an ARV illness, or to determine the presence of a latent respiratory viral infection in the subject.
(canceled)
A system for determining the presence of and/or determining an etiology of an acute respiratory viral illness in a subject comprising:
- (i) at least one processor;
- (ii) a sample input circuit configured to receive a biological sample from the subject;
- (iii) a sample analysis circuit coupled to the at least one processor and configured to determine gene product expression levels of the biological sample;
- (iv) an input/output circuit coupled to the at least one processor;
- (v) a storage circuit coupled to the at least one processor and configured to store data, parameters, and/or classifiers;
- and
- (vi) a memory coupled to the processor and comprising computer readable program code embodied in the memory that when executed by the at least one processor causes the at least one processor to perform operations comprising:
- (a) controlling/performing measurement via the sample analysis circuit of protein and/or peptide expression levels of a pre-defined set of gene products in said biological sample;
- (b) normalizing the gene product expression levels to generate normalized gene product expression values;
- retrieving from the storage circuit an ARV classifier, said classifier(s) comprising predefined weighting values for each of the pre-defined set of gene products;
- (c) entering the normalized gene product expression values into one or more acute respiratory viral illness classifiers selected from the ARV classifier;
- (d) calculating a presence and/or etiology probability for an ARV illness based upon said classifier(s), and optionally determining a threshold for the determination of ARV illness;
- and
- (e) controlling output via the input/output circuit of a determination of the presence of, or the etiology of, the acute respiratory viral illness in the subject.
A method for determining the presence or absence of a respiratory virus in a population of subjects comprising, consisting of, or consisting essentially of:
- (a) obtaining a biological sample from each of the subjects;
- (b) measuring on a platform expression levels of a pre-defined set of gene products in each of the biological samples;
- (c) normalizing the gene product expression levels to generate normalized expression values;
- (d) entering the normalized gene product expression values into one or more acute respiratory virus illness classifiers, said classifier(s) comprising pre-defined weighting values for each of the gene products of the pre-determined set of proteins and/or peptides for the platform, optionally wherein said classifier(s) are retrieved from one or more databases;
- and
- (e) calculating presence probability for an ARV illness based upon said normalized expression values and said classifier(s), to thereby determine the presence or absence of a respiratory virus in the population of subjects.
39-41. (canceled)
A method for determining whether an antibacterial therapy should administered to a subject suffering from a respiratory infection comprising, consisting of, or consisting essentially of:
- (a) obtaining a biological sample from the subject;
- (b) measuring on a platform expression levels of a pre-defined set of gene products in said biological sample;
- (c) normalizing the gene product expression levels to generate normalized expression values;
- (d) entering the normalized gene product expression values into one or more acute respiratory virus (ARV) illness classifiers, said classifier(s) comprising pre-defined weighting values for each of the gene products of the pre-determined set of proteins and/or peptides for the platform, optionally wherein said classifier(s) are retrieved from one or more databases;
- (e) calculating presence probability for one or more ARV illnesses based upon said normalized expression values and said classifier(s), to thereby determine the presence of a respiratory virus infection in the subject;
- and
- (f) not administering to the subject an antibacterial therapy if the presence of a respiratory virus is determined.
A kit for determining the presence or absence of viral etiology of an ARV illness in a subject, or for detecting the presence or absence of a respiratory virus in a subject, comprising:
- (a) a means for extracting a biological sample;
- (b) a means for generating one or more arrays consisting of a plurality of antibodies or other analyte specific reagents for use in measuring gene product expression levels of a pre-defined set of gene products;
- and
- (c) optionally, instructions for use.
(canceled)
Dependencies are inferred from the claim text.