WO2020112149A1 - Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami) - Google Patents

Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami) Download PDF

Info

Publication number
WO2020112149A1
WO2020112149A1 PCT/US2018/063517 US2018063517W WO2020112149A1 WO 2020112149 A1 WO2020112149 A1 WO 2020112149A1 US 2018063517 W US2018063517 W US 2018063517W WO 2020112149 A1 WO2020112149 A1 WO 2020112149A1
Authority
WO
WIPO (PCT)
Prior art keywords
ami
cer
panel
subject
sample
Prior art date
Application number
PCT/US2018/063517
Other languages
English (en)
Inventor
Bruce Xuefeng Ling
Linmin CHEN
Shiying Hao
Original Assignee
Binhai Industrial Technology Research Institute Of Zhejiang University
Tianjin Yunjian Medical Technology Co., Ltd.
Mprobe Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Binhai Industrial Technology Research Institute Of Zhejiang University, Tianjin Yunjian Medical Technology Co., Ltd., Mprobe Inc. filed Critical Binhai Industrial Technology Research Institute Of Zhejiang University
Priority to PCT/US2018/063517 priority Critical patent/WO2020112149A1/fr
Publication of WO2020112149A1 publication Critical patent/WO2020112149A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2570/00—Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction

Definitions

  • compositions for providing an assessment of acute myocardial infarction using four Ceram ides and their ratios as total 6 analytic markers are provided.
  • AMI Acute myocardial infarction
  • U unstable angina pectoris
  • ACS acute coronary syndrome
  • CAD coronary artery disease
  • CAD and AMI The current clinical diagnosis of CAD and AMI bases on patient symptoms, electrocardiogram (ECG), cardiac markers, stress testing, and coronary angiography. Invasive coronary angiography is the diagnostic“gold standard”, but its specialized technology and high cost limit it to a select population. Abnormal metabolism also characterizes CAD and AMI. Metabolic alterations in the heart result in changes in the metabolome of biofluids. A combination of multiple small-molecule metabolites or their ratios may offer excellent diagnostic values. Thus, there is a need to discover CAD and AMI biomarkers underlying the pathogenetic pathways and construct a more accurate biomarker panels that can provide a definitive early diagnosis, better monitoring, leading to improved outcomes and economic benefits.
  • AMI biomarkers AMI biomarker panels, and methods obtaining AMI biomarker level representation for a sample are provided. These composition and methods find use in a number of applications, including, for example, diagnosing AMI, prognosing AMI, monitoring a subject with AMI, and determining a therapy for AMI. In addition, systems, devices, and kits thereof that find use in practicing the subject methods are provided.
  • a panel of AMI biomarkers is provided, the panel comparing one or more AMI markers selected from the ceramide group consisting of Cer(18:1/18:0), Cer(18:1/16:0), Cer(18:1/24:1 ), Cer(18:1/18:0)/24:0,
  • a method for providing an AMI marker level representation for a subject.
  • the method comprises evaluating a panel of AMI markers in a serum sample from a subject to determine the level of each AMI marker in the serum sample; and obtaining the AMI marker level representation based on the level of each AMI marker in the panel.
  • the panel comprises Cer(18: 1/18:0). In some embodiments, the panel comprises Cer(18:1 /16:0) and Cer(18: 1/24:1 ). In some embodiments, the panel further comprises one or more AMI markers selected from the group consisting of
  • the panel comprises all AMI markers froom the group consisting of Cer(18: 1/18:0),
  • the method further comprises providing a report of the AMI marker level representation.
  • the AMI marker representation is an AMI score.
  • kits for the analysis of a sample of a bio-fluid of a subject comprising aliquots of standards of each compound of a panel of metabolite species; an aliquot of an internal standard; and an aliquot of a control bio-fluid.
  • the control bio-fluid is serum from a control source that is conspecific with the subject.
  • the internal standard consists of D 7 -d18:1 -16:0 Ceramide, D 7 -d18:1 -18:0 Ceramide, D 7 -d18: 1 -24:0 Ceramide, D 7 - d18: 1 -24:1 Ceramide.
  • the kit includes instructions for use. Brief description of the drawings
  • ceramides analytes Cer(18: 1 /18:0), Cer(18:1/16:0), Cer(18: 1/24: 1 ), and their ratios to Cer(18: 1/24:0) in case, control, and testing samples in serum.
  • AMI biomarkers AMI biomarker panels, and methods obtaining AMI biomarker level representation for a sample are provided. These composition and methods find use in a number of applications, including, for example, diagnosing AMI, prognosing AMI, monitoring a subject with AMI, and determining a therapy for AMI. In addition, systems, devices, and kits thereof that find use in practicing the subject methods are provided.
  • compositions, methods, systems and kits that find use in providing an AMI assessment, e.g.
  • AMI it is meant an acute multisystem complication of partial or complete coronary arteries blockage that may be accompanied by one or more of hypoperfusion of myocardial tissue, brain ischemia, and systemic hypoxia, ischemia, and multiple organs failure.
  • compositions useful for providing an AMI assessment will be described first, followed by methods, systems and kits for their use.
  • AMI biomarkers are provided.
  • an“AMI biomarker” it is meant a molecular entity whose representation in a sample is
  • an AMI marker may be differentially represented, i.e. represented at a different level, in a sample from an individual that has developed AMI as compared to a healthy individual.
  • an elevated level of marker is associated with the AMI phenotype.
  • the concentration of marker in a sample may be 1.5-fold, 2-fold, 2.5-fold, 3-fold, 4-fold, 5-fold, 7.5-fold, 10- fold, or greater in a sample associated with the AMI phenotype than in a sample not associated with the AMI phenotype.
  • a reduced level of marker is associated with the AMI phenotype.
  • the concentration of marker in a sample may be 10% less, 20% less, 30% less, 40% less, 50% less or more in a sample associated with the AMI phenotype than in a sample not associated with the AMI phenotype.
  • the inventors have identified 6 ceramides or their ratios that are associated with AMI and that find use in combination (ie. as a panel) in providing an AMI assessment, e.g. diagnosing AMI, prognosing AMI, monitoring a subject with AMI, determining a treatment for a subject affected with AMI, and the like.
  • AMI assessment e.g. diagnosing AMI, prognosing AMI, monitoring a subject with AMI, determining a treatment for a subject affected with AMI, and the like.
  • These include, but are not limited to: Cer(18:1/18:0), Cer(18:1/16:0), Cer(18: 1/24:1 ), Cer(18:1/18:0)/24:0, Cer(18:1/16:0)/24:0,
  • Cer(18:1/24:1 )/24:0 that are represented at elevated levels in blood samples of AMI, and thus, that find use as biomarkers in providing an AMI assessment, e.g. diagnosing an AMI, prognosing an AMI, determining a treatment for a subject affected with AMI, monitoring a subject with AMI, and the like.
  • AMI panels By a“panel” of AMI markers it is meant two or more AMI markers, e.g. 2 or more, 3 or more, 4 or more, or 5 or more markers, whose levels, when considered in combination, find use in providing AMI assessment, e.g. making AMI diagnosis, prognosis, monitoring, and/or treatment.
  • ceramide panels that comprise the AMI marker Cer(18:1/18:0), Cer(18:1/16:0), Cer(18: 1/24:1 ), Cer(18:1/18:0)/24:0, Cer(18:1/16:0)/24:0, and Cer(18:1/24:1 )/24:0.
  • the AMI panel may comprise Cer(18: 1 /18:0) and Cer(18:1/16:0), or Cer(18:1/18:0) and Cer(18: 1/24:1 ), or
  • AMI markers that find use as AMI panels in the subject methods may be readily identified by the ordinarily skilled artisan using any convenient statistical methodology, e.g. as known in the art or described in the working examples herein.
  • an AMI marker level representation it is meant a representation of the levels of one or more of the subject AMI marker(s), e.g. a panel of AMI markers, in a biological sample from a subject.
  • biological sample encompasses a variety of sample types obtained from an organism and can be used in a diagnostic, prognostic, or monitoring assay.
  • the term encompasses blood and other liquid samples of biological origin or cells derived therefrom and the progeny thereof.
  • the term encompasses samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, or enrichment for certain components.
  • AMI assessment it is generally meant an estimation of a subject's susceptibility to AMI, a determination as to whether a subject is presently affected by AMI, a prognosis of a subject affected by AMI (e.g., identification of AMI states), and the use of therapeutics (e.g., monitoring a subject's condition to provide information as to the effect or efficacy of therapy on the AMI).
  • the subject AMI biomarkers and biomarker panels may be used to diagnose AMI, to provide a prognosis to a patient having AMI, to provide a prediction of the responsiveness of a patient with AMI to a medical therapy, to monitor a patient having AMI, to treat a patient having AMI, etc.
  • an AMI biomarker signature for a patient is obtained.
  • AMI biomarker signature or more simply, “ AMI signature”
  • a biomarker signature it is meant a representation of the measured level/activity of an AMI biomarker or biomarker panel of interest.
  • a biomarker signature typically comprises the quantitative data on the biomarker levels/activity of these one or more biomarkers of interest.
  • biomarker signatures include collections of measured small molecular metabolites levels.
  • biomarker signature means metabolites signature.
  • biomarker signatures include biomarker profiles and biomarker scores.
  • biomarker profile it is meant the normalized representation of one or more biomarkers of interest, i.e. a panel of biomarkers of interest, in a patient sample.
  • biomarker score it is meant a single metric value that represents the sum of the weighted representations of one or more biomarkers of interest, more usually two or more biomarkers of interest, i.e. a panel of biomarkers of interest, in a patient sample. Biomarker profiles and scores are discussed in greater detail below.
  • the subject methods may be used to obtain an AMI signature. That is, the subject methods may be used to obtain a representation of the metabolite, e.g. Cer(18:1/18:0), Cer(18:1/16:0), Cer(18: 1/24:1 ),
  • the metabolite level of the one or more AMI biomarkers of interest is detected in a patient sample. That is, the representation of one or more AMI biomarkers, e.g., Cer(18:1/18:0), Cer(18:1/16:0), Cer(18: 1/24:1 ),
  • sample with respect to a patient encompasses blood and other liquid samples of biological origin, solid tissue samples such as a biopsy specimen or tissue cultures or cells derived or isolated therefrom and the progeny thereof.
  • the definition also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents; washed; or enrichment for certain cell populations.
  • the definition also includes samples that have been enriched for particular types of molecules, e.g., nucleic acids, polypeptides, etc.
  • biological sample encompasses a clinical sample, and also includes tissue obtained by surgical resection, tissue obtained by biopsy, cells in culture, cell supernatants, cell lysates, tissue samples, organs, bone marrow, blood, plasma, serum, and the like.
  • blood sample encompasses a blood sample (e.g., peripheral blood sample) and any derivative thereof (e.g., fractionated blood, plasma, serum, etc.).
  • the biomarker level is typically assessed in a body fluid sample (e.g., a sample of blood, e.g., whole blood, fractionated blood, plasma, serum, etc.) that is obtained from an individual.
  • a body fluid sample e.g., a sample of blood, e.g., whole blood, fractionated blood, plasma, serum, etc.
  • the sample that is collected may be freshly assayed or it may be stored and assayed at a later time. If the latter, the sample may be stored by any convenient means that will preserve the sample so that gene expression may be assayed at a later date.
  • the sample may freshly cryopreserved, that is, cryopreserved without impregnation with fixative, e.g. at 4°C, at - 20°C, at -60°C, at -80°C, or under liquid nitrogen.
  • the sample may be fixed and preserved, e.g. at room temperature, at 4°C, at -20°C, at -60°C, at -80°C, or under liquid nitrogen, using any of a number of fixatives known in the art, e.g. alcohol, methanol, acetone, formalin, paraformaldehyde, etc.
  • fixatives e.g. alcohol, methanol, acetone, formalin, paraformaldehyde, etc.
  • the resultant data provides information regarding activity for each of the AMI biomarkers that have been measured, wherein the information is in terms of whether or not the biomarker is present (e.g. expressed and/or active) and, typically, at what level, and wherein the data may be both qualitative and quantitative.
  • the measurement(s) may be analyzed in any of a number of ways to obtain a biomarker signature.
  • the representation of the one or more AMI biomarkers may be analyzed individually to develop a biomarker profile.
  • a biomarker profile is the normalized representation of one or more biomarkers in a patient sample, for example, the normalized level of serological metabolite concentrations in a patient sample, the normalized activity of a biomarker in the sample, etc.
  • a profile may be generated by any of a number of methods known in the art. Other methods of calculating a biomarker signature will be readily known to the ordinarily skilled artisan.
  • the measurement of an AMI biomarker or biomarker panel may be analyzed collectively to arrive at an AMI biomarker score, and the AMI biomarker signature is therefore a single score.
  • biomarker assessment score it is meant a single metric value that represents the sum of the weighted representations of each of the biomarkers of interest, more usually two or more biomarkers of interest, in a biomarker panel.
  • the subject method comprises detecting the amounts of markers of an AMI biomarker panel in the sample, and calculating an AMI biomarker score based on the weighted levels of the biomarkers.
  • the biomarker score is based on the weighted levels of the biomarkers.
  • the biomarker score may be a“metabolite biomarker score”, or simply“metabolite score”, i.e. it comprises the weighted expression level(s) of the one or more biomarkers, e.g. each biomarker in a panel of biomarkers.
  • the weighting factor, or simply "weight" for each marker in a panel may be a reflection of the change in analyte level in the sample.
  • the analyte level of each biomarker may be log2 transformed and weighted either as 1 (for those markers that are increased in level in a group of AMI of interest, etc.) or -1 (for those markers that are decreased in level in a group of AMI of interest, etc.), and the ratio between the sum of increased markers as compared to decreased markers determined to arrive at an AMI biomarker signature.
  • the weights may be reflective of the importance of each marker to the specificity, sensitivity and/or accuracy of the marker panel in making the diagnostic, prognostic, or monitoring assessment.
  • weights may be determined by any convenient statistical machine learning methodology, e.g. Principle Component Analysis (PCA), linear regression, support vector machines (SVMs), and/or random forests of the dataset from which the sample was obtained may be used.
  • PCA Principle Component Analysis
  • SVMs support vector machines
  • weights for each marker are defined by the dataset from which the patient sample was obtained.
  • weights for each marker may be defined based on a reference dataset, or“training dataset”.
  • Methods of analysis may be readily performed by one of ordinary skill in the art by employing a computer-based system, e.g. using any hardware, software and data storage medium as is known in the art, and employing any algorithms convenient for such analysis. For example, data mining algorithms can be applied through“cloud computing”, smartphone based or client-server based platforms, and the like.
  • an AMI biomarker signature may be expressed as a series of values that are each reflective of the level of a different biomarker (e.g., as a biomarker profile, i.e. the normalized expression values for multiple biomarkers), while in other instances, the AMI biomarker signature may be expressed as a single value (e.g., an AMI biomarker score).
  • the subject methods of obtaining or providing an AMI biomarker signature for a subject further comprise providing the AMI biomarker signature as a report.
  • the subject methods may further include a step of generating or outputting a report providing the results of an AMI biomarker evaluation in the sample, which report can be provided in the form of an electronic medium (e.g., an electronic display on a computer monitor), or in the form of a tangible medium (e.g., a report printed on paper or other tangible medium). Any form of report may be provided, e.g. as known in the art or as described in greater detail below.
  • the AMI signature that is so obtained may be employed to make an
  • the AMI signature is employed by comparing it to a reference or control, and using the results of that comparison (a“comparison result”) to make the AMI assessment, e.g. diagnosis, prognosis, prediction of responsiveness to treatment, etc.
  • the terms“reference” or “control”, e.t.“reference signature” or“control signature”,“reference profile” or“control profile”, and“reference score” or“control score” as used herein mean a standardized biomarker signature, e.g. biomarker profile or biomarker score, that may be used to interpret the AMI biomarker signature of a given patient and assign a diagnostic, prognostic, and/or responsiveness class thereto.
  • the reference or normal control is typically an AMI biomarker signature that is obtained from a sample (e.g., a body fluid, e.g. blood) with a known association with a particular phenotype, Typically, the comparison between the AMI signature and reference will determine whether the AMI signature correlates more closely with the positive reference or the negative reference, and the correlation employed to make the assessment.
  • AMI biomarker signature that is obtained from a sample (e.g., a body fluid, e.g. blood) with a known association with a particular phenotype.
  • the comparison between the AMI signature and reference will determine whether the AMI signature correlates more closely with the positive reference or the negative reference, and the correlation employed to make the assessment.
  • correlates closely it is meant is within about 40% of the reference, e.g. 40%, 35%, or 30%, in some
  • embodiments within 25%, 20%, or 15%, sometimes within 10%, 8%, 5%, or less.
  • the obtained AMI signature for a subject is compared to a single reference/control biomarker signature to obtain information regarding the phenotype.
  • the obtained biomarker signature for the subject is compared to two or more different reference/control biomarker signatures to obtain more in-depth information regarding the phenotype of the assayed tissue.
  • a biomarker profile, or a biomarker score to obtain confirmed information regarding whether the tissue has the phenotype of interest.
  • a biomarker profile or score may be compared to multiple biomarker profiles or scores, each correlating with a particular diagnosis, prognosis or therapeutic responsiveness.
  • A“report,” as described herein, is an electronic or tangible document which includes report elements that provide information of interest relating to a diagnosis assessment, a prognosis assessment, a treatment assessment, a monitoring
  • a subject report can be completely or partially electronically generated.
  • a subject report includes at least an AMI assessment, e.g., a diagnosis as to whether a subject has a high likelihood of having an AMI.
  • a subject report can further include one or more of: 1 ) information regarding the testing facility; 2) service provider information; 3) patient data; 4) sample data; 5) an assessment report, which can include various information: a) reference values employed, and b) test data, where test data can include: i) the biomarker levels of one or more AMI biomarkers, and/or ii) the biomarker signatures for one or more AMI biomarkers; 6) other features.
  • providing an AMI signature or providing an AMI assessment includes generating a written report that includes AMI signature and/or the AMI assessment e.g. a "diagnosis assessment", a suggestion of possible treatment regimens (a "treatment assessment") and the like.
  • the subject methods may further include a step of generating or outputting a report providing the results of an analysis of an AMI biomarker or biomarker panel, a diagnosis assessment, a prognosis assessment, or a treatment assessment, which report can be provided in the form of an electronic medium (e.g., an electronic display on a computer monitor), or in the form of a tangible medium (e.g., a report printed on paper or other tangible medium).
  • the report may include information about the testing facility, which information is relevant to the hospital, clinic, or laboratory in which sample gathering and/or data generation was conducted. This information can include one or more details relating to, for example, the name and location of the testing facility, the identity of the lab technician who conducted and/or analyzed, the location where the sample and/or result data is stored, the lot number of the reagents (e.g., kit, etc.) used in the assay, and the like. Report fields with this information can generally be populated using information provided by the user.
  • the report may include information about the service provider, which may be located outside the healthcare facility at which the user is located, or within the healthcare facility. Examples of such information can include the name and location of the service provider, the name of the reviewer, and where necessary or desired the name of the individual who conducted sample gathering and/or data generation. Report fields with this information can generally be populated using data entered by the user, which can be selected from among pre-scripted selections (e.g., using a drop-down menu). Other service provider information in the report can include contact information for technical information about the result and/or about the interpretive report.
  • the report may include a patient data section, including patient medical history as well as administrative patient data such as information to identify the patient (e.g., name, patient date of birth (DOB), gender, mailing and/or residence address, medical record number (MRN), room and/or bed number in a healthcare facility), insurance information, and the like), the name of the patient's physician or other health
  • patient medical history as well as administrative patient data such as information to identify the patient (e.g., name, patient date of birth (DOB), gender, mailing and/or residence address, medical record number (MRN), room and/or bed number in a healthcare facility), insurance information, and the like), the name of the patient's physician or other health
  • administrative patient data such as information to identify the patient (e.g., name, patient date of birth (DOB), gender, mailing and/or residence address, medical record number (MRN), room and/or bed number in a healthcare facility), insurance information, and the like), the name of the patient's physician or other health
  • a staff physician who is responsible for the patient's care (e.g., primary care physician).
  • the report may include a sample data section, which may provide information about the biological sample analyzed in the monitoring assessment, such as the source of biological sample obtained from the patient (e.g. blood, saliva, or type of tissue, etc.), how the sample was handled (e.g. storage temperature, preparatory protocols) and the date and time collected. Report fields with this information can generally be populated using data entered by the user, some of which may be provided as pre-scripted selections (e.g., using a drop-down menu).
  • the reports can include additional elements or modified elements.
  • the report can contain hyperlinks which point to internal or external databases which provide more detailed information about selected elements of the report.
  • the patient data element of the report can include a hyperlink to an electronic patient record, or a site for accessing such a patient record, which patient record is maintained in a confidential database.
  • This latter embodiment may be of interest in an in-hospital system or in-clinic setting.
  • the report is recorded on a suitable physical medium, such as a computer readable medium, e.g., in a computer memory, zip drive, CD, DVD, etc.
  • the report can include all or some of the elements above, with the proviso that the report generally includes at least the elements sufficient to provide the analysis requested by the user (e.g. a diagnosis, a prognosis).
  • reagents, devices and kits thereof for practicing one or more of the above-described methods.
  • the subject reagents, devices and kits thereof may vary greatly.
  • Reagents and devices of interest include those mentioned above with respect to the methods of assaying metabolites levels, where such reagents may include stable isotope labeled internal standards D 7 -d18: 1 -16:0 Ceramide, D 7 -d18: 1 -18:0 Ceramide, D 7 -d18: 1-24:0 Ceramide, D 7 - d18: 1 -24:1 Ceramide.
  • the subject kits may also comprise one or more biomarker signature references, e.g. a reference for an AMI signature, for use in employing the biomarker signature obtained from a patient sample.
  • the reference may be a sample of a known phenotype, e.g. an unaffected individual, or an affected individual, e.g. from a particular risk group that can be assayed alongside the patient sample, or the reference may be a report of disease diagnosis, disease prognosis, or responsiveness to therapy that is known to correlate with one or more of the subject AMI biomarker signatures.
  • the subject kits may further include instructions for practicing the subject methods. These instructions may be present in the subject kits in a variety of forms, one or more of which may be present in the kit.
  • One form in which these instructions may be present is as printed information on a suitable medium or substrate, e.g., a piece or pieces of paper on which the information is printed, in the packaging of the kit, in a package insert, etc.
  • Yet another means would be a computer readable medium, e.g., diskette, CD, DVD, etc., on which the information has been recorded.
  • Yet another means that may be present is a website address which may be used via the internet to access the information at a removed site. Any convenient means may be present in the kits.
  • a biological analysis of pathway related to the development and progression of AMI was conducted through a metabolomics approach integrated with statistical learning technologies.
  • a literature review was conducted in parallel to identify markers associated with AMI.
  • the results of the two approaches were integrated to generate a hypothesis that Cer(18: 1/18:0), Cer(18: 1/16:0), Cer(18:1/24:1 ), Cer(18:1/18:0)/24:0, Cer(18:1/16:0)/24:0, Cer(18:1/24:1 )/24:0 can be used for AMI assessment.
  • the AMI and normal control subjects were used for serological protein biomarker discovery and validation. Internal standard preparation
  • Serum sample was taken from -80 °C freezer and thawed on ice.10 pL of each serum sample was transferred into a new tube, and 90 pL 10 extraction buffer was added for extraction. The samples were vortexed vigorously for 1 min and subjected to high-speed centrifuge at 12,000 g for 5 min under room
  • HESI Heated electrospray ionization
  • Ion transfer tube temperature 350 °C
  • Vaporizer temperature 250 °C
  • SRM Selected-reaction monitoring

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Endocrinology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne des biomarqueurs de l'infarctus du myocarde aigu (AMI), des panels de biomarqueurs AMI, et des procédés permettant d'obtenir une représentation du niveau de biomarqueur AMI pour un échantillon. Ces compositions et méthodes sont utilisables dans un certain nombre d'applications telles que, par exemple, la stadification de AMI, le diagnostic de AMI, le pronostic de AMI, la surveillance d'un sujet atteint de AMI et la détermination d'un traitementpour AMI. L'invention concerne en outre des systèmes, des dispositifs et des trousses associés, utilisables dans la mise en pratique desdites méthodes.
PCT/US2018/063517 2018-12-01 2018-12-01 Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami) WO2020112149A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2018/063517 WO2020112149A1 (fr) 2018-12-01 2018-12-01 Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2018/063517 WO2020112149A1 (fr) 2018-12-01 2018-12-01 Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami)

Publications (1)

Publication Number Publication Date
WO2020112149A1 true WO2020112149A1 (fr) 2020-06-04

Family

ID=70853116

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/063517 WO2020112149A1 (fr) 2018-12-01 2018-12-01 Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami)

Country Status (1)

Country Link
WO (1) WO2020112149A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013068374A2 (fr) * 2011-11-08 2013-05-16 Zora Biosciences Oy Biomarqueurs lipidomiques pour prédire l'évolution de maladies cardiovasculaires chez des patients atteints de coronaropathie et suivant un traitement par statine
WO2015193325A2 (fr) * 2014-06-16 2015-12-23 Zora Biosciences Oy Céramides et leur utilisation dans le diagnostic de maladies cardiovasculaires
US20170023575A1 (en) * 2013-08-21 2017-01-26 Purdue Research Foundation Identification of blood based metabolite biomarkers of pancreatic cancer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013068374A2 (fr) * 2011-11-08 2013-05-16 Zora Biosciences Oy Biomarqueurs lipidomiques pour prédire l'évolution de maladies cardiovasculaires chez des patients atteints de coronaropathie et suivant un traitement par statine
US20170023575A1 (en) * 2013-08-21 2017-01-26 Purdue Research Foundation Identification of blood based metabolite biomarkers of pancreatic cancer
WO2015193325A2 (fr) * 2014-06-16 2015-12-23 Zora Biosciences Oy Céramides et leur utilisation dans le diagnostic de maladies cardiovasculaires

Similar Documents

Publication Publication Date Title
US20240201201A1 (en) Biomarker Database Generation and Use
Vasan Biomarkers of cardiovascular disease: molecular basis and practical considerations
JP2020034573A (ja) マルチマーカーリスク層別化
Dona et al. Translational and emerging clinical applications of metabolomics in cardiovascular disease diagnosis and treatment
JP2016520192A (ja) 腎機能に関連付けられるバイオマーカーおよびそれを使用する方法
Bowler et al. New strategies and challenges in lung proteomics and metabolomics. An official American Thoracic Society workshop report
US20150018238A1 (en) Multi-biomarker-based outcome risk stratification model for pediatric septic shock
SA516380503B1 (ar) مركبات سيراميد واستخدامها في تشخيص cvd
Karampitsakos et al. The role of increased red cell distribution width as a negative prognostic marker in patients with COPD
Shah et al. Reclassification of cardiovascular risk using integrated clinical and molecular biosignatures: Design of and rationale for the Measurement to Understand the Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Horizon 1 Cardiovascular Disease Study
JP2015507205A (ja) 有害事象のリスク因子および予測
Moon et al. Diagnostic value of parameters related to white blood cell counts for troponin I elevation in CO poisoning
Huang et al. The predictive value of the HEART and GRACE scores for major adverse cardiac events in patients with acute chest pain
WO2018136085A1 (fr) Procédés et compositions permettant de fournir une évaluation d'un cancer de l'ovaire à un stade précoce avec des métabolites
Chen et al. OMICmAge: An integrative multi-omics approach to quantify biological age with electronic medical records
WO2018174876A1 (fr) Méthodes et compositions d'évaluation de la pré-éclampsie à l'aide de métabolites
US20110136241A1 (en) Type ii diabetes molecular bioprofile and method and system of using the same
CN112986454A (zh) 急性心肌梗死的血清标志物、试剂盒和用途
Nallagangula et al. Evolution of proteomic biomarker for chronic liver disease: promise into reality
Varghese et al. Identification of diagnostic urinary biomarkers for acute kidney injury
WO2020112149A1 (fr) Procédés et compositions pour l'évaluation d'un infarctus du myocarde aigu (ami)
Howie et al. The measurement of brain natriuretic peptide in heart failure: precision, accuracy, and implications for practice
CN116500179B (zh) 一种血浆中神经酰胺相关因子的原始得分计算及转换方法和系统
WO2020117184A1 (fr) Méthodes et compositions permettant une évaluation de la pré-éclampsie par la protéomique
Qingwen Chen et al. OMICmAge: An integrative multi-omics approach to quantify biological age with electronic

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18941258

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18941258

Country of ref document: EP

Kind code of ref document: A1