Methods of using a multi-analyte approach for diagnosis and staging a disease
AssigneeThe Trustees of the University of Pennsylvania
InventorsDavid Aaron ISSADORE, Zijian YANG, Erica L. CARPENTER, Ben Z. STANGER
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Abstract
Disclosed herein are methods for evaluating a disease or a condition in a subject. More particularly, disclosed herein are methods for determining or diagnosing a disease, methods for classifying a stage of a disease, methods for treating a disease or methods for assessing the efficacy of a therapy for treating a disease based on the measurement and the computational analysis of various disease-specific biomarkers.
Claims64
A method of determining whether a subject suffers from a disease or a condition, the method comprising:
- a. measuring, in a processed sample from the subject, a set of circulating biomarkers comprising an extra-cellular vesicle (EV) miRNA, an EV mRNA, a circulating cell-free DNA, a circulating tumor DNA, and a protein biomarker specific for the disease or the condition;
- b. applying a machine learning algorithm on the set of circulating biomarkers to generate an output indicative of a disease or a condition state of the subject;
- c. determining whether the subject has the disease or the condition based upon the output so generated;
- and
- d. treating the subject as needed.
A method of classifying a stage of a disease or a condition in a subject in need thereof, the method comprising:
- a. measuring, in a processed sample from the subject, a set of circulating biomarkers comprising an extra-cellular vesicle (EV) miRNA, an EV mRNA, a circulating cell-free DNA, a circulating tumor DNA, and a protein biomarker specific for the disease or the condition;
- b. applying a machine learning algorithm on the set of circulating biomarkers to generate an output indicative of the stage of the disease or the condition of the subject;
- c. determining the stage of the disease or the condition in the subject based upon the output so generated;
- and
- d. recommending treatment or surgery for the subject.
A method of assessing the efficacy of a therapy for treating a disease or a condition in a subject, the method comprising:
- a. measuring, in a first processed sample taken from the subject before treatment, a set of circulating biomarkers comprising an extra-cellular vesicle (EV) miRNA, an EV mRNA, a circulating cell-free DNA, a circulating tumor DNA, and a protein biomarker specific for the disease or the condition;
- b. measuring, in a second processed sample taken from the subject during or after treatment, the same set of circulating biomarkers from step (a);
- c. applying a machine learning algorithm on the circulating biomarkers from step (a) and step (b) to generate a first output and a second output respectively indicative of a stage of the disease or the condition in the subject;
- and
- d. determining a differential between the first output and second output, thereby assessing whether the efficacy of the therapy for treating the disease or the condition in the subject.
A method of determining whether a subject suffers from a disease or a condition, the method comprising:
- a. measuring, in a processed sample from the subject, a set of a plurality of circulating biomarkers selected by machine learning such that each biomarker is indicative of the disease or condition and such that the correlation between the circulating biomarkers is minimized;
- b. generating an output, optionally by a machine learning algorithm, that is indicative of a disease or a condition state of the subject;
- c. determining whether the subject has the disease or the condition based upon the output so generated;
- and
- d. treating the subject as needed.
The method of any one of the preceding claims, wherein the disease or the condition is a cancer.
The method of any one of the preceding claims, wherein the EV miRNA comprises hsa.miR.103b, hsa.miR.23a.3p, hsa.miR.409.3p, hsa.miR.224.5p and hsa.miR.1299.
The method of any one of the preceding claims, wherein the EV mRNA comprises CD63, CK18, GAPDH, H3F3A, KRAS and ODC1.
The method of any one of the preceding claims, wherein the ccfDNA comprises an ALU repetitive element.
The method of any one of the preceding claims, wherein the ctDNA comprises a mutated KRAS DNA with mutation KRASG12D, KRASG12V or KRASG12R.
The method of any one of the preceding claims, wherein the protein biomarker is a cancer antigen protein.
The method of any one of the preceding claims, wherein the protein biomarker is cancer antigen 19-9 (CA19-9) protein.
The method of any one of the preceding claims, wherein the circulating biomarkers comprise at least hsa.miR.1299, GAPDH mRNA, a mutated KRAS DNA and CA19-9 protein.
The method of any one of the preceding claims, wherein the processed sample is taken from whole blood or plasma.
The method of any one of the preceding claims, wherein the processed sample comprises extracted, amplified and/or labeled DNA, RNA or protein.
The method of any one of the preceding claims, wherein the EV miRNA and EV mRNA are extracted by a track etched magnetic nanopore (TENPO) device.
The method of any one of the preceding claims, wherein one or more of the circulating biomarkers are measured by one or more of sequencing, quantitative PCR, digital PCR, or immunoassay.
The method of any one of the preceding claims, wherein the machine learning algorithm distinguishes the circulating biomarkers from a control.
A method of determining whether a subject suffers from a disease or condition, comprising:
- a. isolating a biological sample from the subject, using a magnetic separation filter device, wherein the magnetic separation filter device comprises a layer of magnetically soft material and a plurality of pores extending through the layer of magnetically soft material;
- b. analyzing two or more biomarkers from the biological sample to generate an output;
- and
- c. determining whether the subject has the disease or condition based upon the output so generated.
A method of diagnosing a disease or condition in a subject, comprising:
- a. isolating a biological sample from the subject, using a magnetic separation filter device, wherein the magnetic separation filter device comprises a layer of magnetically soft material and a plurality of pores extending through the layer of magnetically soft material;
- b. analyzing two or more biomarkers from the biological sample to generate an output;
- and
- c. diagnosing the disease or condition in the subject based upon the output so generated.
A method of treating a disease or condition in a subject, comprising:
- a. isolating a biological sample from the subject, using a magnetic separation filter device, wherein the magnetic separation filter device comprises a layer of magnetically soft material and a plurality of pores extending through the layer of magnetically soft material;
- b. analyzing two or more biomarkers from the biological sample to generate an output;
- c. diagnosing the disease or condition in the subject based upon the output so generated;
- and
- d. administering a therapeutically effective amount of a drug suitable for treating the disease or condition to the subject.
Dependencies are inferred from the claim text.