CN116875673A - System for diagnosing myocardial infarction - Google Patents
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- CN116875673A CN116875673A CN202211540767.4A CN202211540767A CN116875673A CN 116875673 A CN116875673 A CN 116875673A CN 202211540767 A CN202211540767 A CN 202211540767A CN 116875673 A CN116875673 A CN 116875673A
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Classifications
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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- 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
Abstract
The invention discloses a system for diagnosing myocardial infarction. The invention provides a calculation model, a system or a device for diagnosing myocardial infarction, which comprises the steps of inputting or detecting the expression level of KIF3A and/or OXCT1 to diagnose myocardial infarction, has higher sensitivity and specificity, can provide a new thought for treating myocardial infarction, and has wide application prospect.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to a system for diagnosing myocardial infarction.
Background
Myocardial infarction (myocardial infarction, MI) is abbreviated as myocardial infarction, one of the most serious of cardiovascular diseases, mainly caused by coronary atherosclerotic thrombosis or myocardial supply and demand imbalance. When an atherosclerotic population forms, the released plaque may accumulate platelets, resulting in occlusion of the coronary arteries, leading to myocardial ischemia and necrosis. Myocardial ischemia causes deprivation of nutrients and oxygen, and various cell death mechanisms (including apoptosis, pyro-death, necrosis, etc.) are activated, while myocardial apoptosis can easily lead to myocardial infarction.
Some typical risk factors, such as high serum cholesterol, hypertension and diabetes, can play a role in alerting the diagnosis of MI, but these are insufficient to fully provide an accurate diagnosis. The myocardial damage substance is a specific substance (mostly protein) existing in myocardial cells, and is released into blood when myocardial cells are damaged, and can be detected in peripheral blood, and is now widely used for diagnosis of MI. However, since myocardial damaging substances are false positives for diagnosis and treatment of MI as diagnostic markers of MI, diagnosis and reperfusion therapy are affected. Therefore, the effective diagnosis and the timely treatment of myocardial infarction are realized, and the survival rate of MI patients is improved.
Disclosure of Invention
In order to make up for the defects of the prior art, the invention provides a system or a device for diagnosing myocardial infarction, the system or the device comprises a processing unit for detecting the expression level of KIF3A and/or OXCT1, and the system or the device provided by the invention has higher diagnosis efficiency on myocardial infarction and has wide clinical application prospect.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a first aspect of the present invention provides a system or device for diagnosing myocardial infarction, the system or device comprising:
(1) An acquisition unit: for obtaining expression levels of KIF3A and/or OXCT1 in a sample from a subject;
(2) And a processing unit: and obtaining a diagnosis result of myocardial infarction according to the expression condition of the KIF3A and/or the OXCT1.
Further, the sample includes blood, tissue.
Further, the sample is selected from blood.
A second aspect of the invention provides a computer readable storage medium having stored thereon a computer program which when executed by a processor implements a system or apparatus according to the first aspect of the invention.
A third aspect of the invention provides a computational model for diagnosing myocardial infarction, the computational model comprising an expression level of input KIF3A and/or OXCT1.
A fourth aspect of the invention provides the use of KIF3A and/or OXCT1 in the construction of a computational model for diagnosing myocardial infarction.
A fifth aspect of the present invention provides an apparatus for diagnosing myocardial infarction, the apparatus comprising a memory for storing program instructions and a processor for invoking the program instructions;
when executed, the program instructions are configured to perform the following:
obtaining data on KIF3A and/or OXCT1 expression levels in a sample from a subject;
and obtaining the diagnosis result of myocardial infarction according to the expression condition of the KIF3A and/or the OXCT1.
In a sixth aspect, the invention provides the use of an agent for detecting the expression level of KIF3A and/or OXCT1 in a sample in the manufacture of a product for diagnosing myocardial infarction.
Further, the agent is selected from an oligonucleotide probe that specifically recognizes KIF3A and/or OXCT1 genes, a primer that specifically amplifies KIF3A and/or OXCT1 genes, or a binding agent that specifically binds to a protein encoded by KIF3A and/or OXCT1 genes.
Further, the sample includes blood, tissue.
Further, the sample is selected from blood.
In a seventh aspect the invention provides a product for diagnosing myocardial infarction, the product comprising reagents for detecting the expression level of KIF3A and/or OXCT1 in a sample.
Further, the product comprises a chip, a kit or a nucleic acid membrane strip.
Further, the chip comprises a gene chip comprising an oligonucleotide probe for KIF3A and/or OXCT1 genes for detecting the transcription level of KIF3A and/or OXCT1 genes, a protein chip comprising a specific binding agent for KIF3A and/or OXCT1 proteins; the kit comprises a gene detection kit and a protein detection kit, wherein the gene detection kit comprises a reagent or a chip for detecting the transcription level of the KIF3A and/or the OXCT1 genes, and the protein detection kit comprises a reagent or a chip for detecting the expression level of the KIF3A and/or the OXCT1 proteins.
Further, the kit comprises reagents for detecting the expression level of KIF3A and/or OXCT1 genes or proteins by RT-PCR, biochip detection, southern blotting, in situ hybridization, immunoblotting, mass spectrometry.
Further, the sample includes blood, tissue.
Further, the sample is selected from blood.
In an eighth aspect, the invention provides the use of KIF3A and/or OXCT1 in the screening of candidate drugs for the treatment of myocardial infarction.
Further, the method for screening candidate drugs for treating myocardial infarction comprises the following steps: treating a culture system expressing or containing KIF3A and/or OXCT1 genes or proteins encoded thereby with a substance to be screened; and detecting expression or activity of KIF3A and/or OXCT1 gene or a protein encoded thereby in the system; wherein the substance to be screened is a candidate drug for treating myocardial infarction when the substance to be screened promotes the expression level or activity of KIF3A and/or OXCT1 gene or a protein encoded thereby.
The invention has the advantages and beneficial effects that:
the invention discovers the correlation between the KIF3A and/or the OXCT1 and myocardial infarction for the first time, further provides a system or a device, equipment and a calculation model for diagnosing myocardial infarction, has higher sensitivity and specificity for diagnosing myocardial infarction by the KIF3A and/or the OXCT1, can realize accurate diagnosis of myocardial infarction, provides a new thought for treating myocardial infarction, and has wide application prospect.
Drawings
FIG. 1 is a graph of batch effect processing results and intersection genes in different datasets, wherein 1A is a graph of experimental batch effect processing results, 1B is a graph of batch effect processing Wen, 1C is a graph of validation batch effect processing results, and 1D is a graph of batch effect processing Wen;
FIG. 2 is a volcanic diagram of a differentially expressed gene;
FIG. 3 is a diagnostic chart of gene expression and ROC, wherein 3A is a graph of KIF3A expression level, 3B is a graph of OXCT1 expression level, 3C is a diagnostic chart of KIF3A ROC, 3D is a diagnostic chart of OXCT1ROC, and 3E is a combined diagnostic chart of KIF3A and OXCT 1;
FIG. 4 is a diagnostic chart of sample gene expression and ROC, wherein 4A is a diagnostic chart of sample KIF3A ROC, 4B is a diagnostic chart of sample OXCT1ROC, and 4C is a combined diagnostic chart of sample KIF3A and OXCT1.
Detailed Description
The following provides definitions of some of the terms used in this specification. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The present invention provides a system or device for diagnosing myocardial infarction, the system or device comprising:
(1) An acquisition unit: for obtaining expression levels of KIF3A and/or OXCT1 in a sample from a subject;
(2) And a processing unit: and obtaining a diagnosis result of myocardial infarction according to the expression condition of the KIF3A and/or the OXCT1.
If the expression level of KIF3A and/or OXCT1 appears to be significantly down-regulated, the subject is indicated to have myocardial infarction.
KIF3A includes wild-type, mutant or fragments thereof. The term encompasses full length, unprocessed KIF3A, as well as any form of KIF3A derived from processing in a cell. The term encompasses naturally occurring variants (e.g., splice variants or allelic variants) of KIF3A. KIF3A includes human KIF3A as well as KIF3A from any other vertebrate source, including mammals, such as primates and rodents (e.g., mice and rats). As a preferred embodiment, in the present invention, KIF3A is a human gene, gene ID 11127.
OXCT1 includes wild-type, mutant or fragments thereof. The term encompasses full length, unprocessed OXCT1, as well as any form of OXCT1 derived from processing in a cell. The term encompasses naturally occurring variants (e.g., splice variants or allelic variants) of OXCT1. OXCT1 comprises human OXCT1 as well as OXCT1 from any other vertebrate source, including mammals, such as primates and rodents (e.g. mice and rats). As a preferred embodiment, in the present invention, OXCT1 is a human gene, gene ID 5019.
In the present invention, "diagnosis," "diagnostic," "making a diagnosis," and variations of these terms refer to the discovery, judgment, or cognition of an individual's health state or condition based on one or more signs, symptoms, data, or other information associated with the individual. The health status of an individual may be diagnosed as healthy/normal (i.e., no disease or condition present) or may be diagnosed as unhealthy/abnormal (i.e., there is an assessment of disease or condition or characteristic). The terms "diagnosis", "diagnostic", "diagnosing" and the like include early detection of a disease in relation to a particular disease or condition; characteristics or classification of disease; discovery of progression, cure, or recurrence of disease; following treatment or therapy of an individual, a response to the disease is found.
The expression level or level in the present invention means the absolute or relative amount of KIF3A and/or OXCT1 in the present invention, and the expression level of any one of KIF3A and/or OXCT1 in the present invention may be determined by various techniques, and in particular, the absolute or relative amount of KIF3A and/or OXCT1 in the present invention may be detected by using methods well known to those skilled in the art.
In the present invention, a "sample" or "specimen" refers to any substance, biological fluid, tissue, or cell obtained or otherwise obtained from an individual. It includes blood (including whole blood, white blood cells, peripheral blood mononuclear cells, buffy coat, plasma, and serum), tissue, sputum, tears, mucus, nasal washes, nasal aspirates, breath-like, urine, semen, saliva, meningeal fluid, amniotic fluid, glandular fluid, lymph, nipple aspirates, bronchial aspirates, synovial fluid, joint aspirates, ascites, cells, cell extracts, and cerebrospinal fluid. It also includes all of the experimentally isolated fractions described above. For example, a blood sample may be fractionated into serum or into fractions containing specific types of blood cells, such as red blood cells or white blood cells (white blood cells). If desired, the sample may be a combination of samples from an individual, such as a combination of tissue and fluid samples. The sample also includes a substance containing a homogeneous solid substance, such as a substance from a fecal sample, a tissue sample, or a biopsy. Samples also include materials derived from tissue culture or cell culture. Any suitable method for obtaining a biological sample may be utilized; exemplary methods include, for example, phlebotomy, wiping (e.g., oral wiping), and fine needle biopsy procedures. Samples may also be collected by, for example, microdissection (e.g., laser Capture Microdissection (LCM) or Laser Microdissection (LMD)), smear (e.g., PAP smear), or catheter lavage. Samples obtained from or derived from an individual include any such samples that are processed in any suitable manner after being obtained from an individual.
In an embodiment of the invention, the sample comprises blood, tissue.
In a specific embodiment of the invention, the sample is selected from blood.
In the present invention, "subject" or "patient" refers to an animal that is capable of suffering from or suffering from myocardial infarction. Examples of subjects include mammals, e.g., humans, non-human primates, dogs, cows, horses, pigs, sheep, goats, cats, mice, rabbits, rats, and transgenic non-human animals.
In an embodiment of the invention, the subject or patient is a human.
The present invention provides a computer readable storage medium having stored thereon a computer program which when executed by a processor implements the above system or apparatus.
In the present invention, a computer-readable storage medium, such as computer-executable code, may take many forms, including but not limited to, tangible storage media, carrier wave media, or physical transmission media. Nonvolatile storage media includes, for example, optical or magnetic disks, such as any storage devices in any computer, volatile storage media including dynamic memory, main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier wave transmission media can take the form of electrical or electromagnetic signals, or acoustic or light waves, such as those generated during radio frequency and infrared data communications. Thus, common forms of computer-readable media include, for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, RAM, ROM, PROM and EPROM, FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, a cable or link transporting such a carrier wave, or any other medium from which a computer can read programming code and/or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.
The present invention provides a computational model for diagnosing myocardial infarction, the computational model comprising KIF3A and/or OXCT1. As the skilled person knows, the step of associating KIF3A and/or OXCT1 levels with a certain possibility or risk may be implemented and realized in different ways. Preferably, the measured concentrations of KIF3A and/or OXCT1 and one or more other markers are mathematically combined and the combined values are correlated with the underlying diagnostic problem. The determination of the marker values may be combined by any suitable prior art mathematical method.
The invention provides application of a reagent for detecting the expression level of KIF3A and/or OXCT1 in a sample in preparing a product for diagnosing myocardial infarction; the reagent is selected from an oligonucleotide probe specifically recognizing KIF3A and/or OXCT1 gene, a primer specifically amplifying KIF3A and/or OXCT1 gene, or a binding agent specifically binding to a protein encoded by KIF3A and/or OXCT1 gene.
In the present invention, the oligonucleotide probes directed against the KIF3A and/or OXCT1 genes may be DNA, RNA, DNA-RNA chimeras, PNA or other derivatives. The length of the probe is not limited, and any length may be used as long as it specifically hybridizes to the target nucleotide sequence and binds thereto. The probe may be as short as 10, 25, 20, 15, 13 or 10 bases in length. Also, the probes can be as long as 60, 80, 100, 150, 300 base pairs or more in length, even for the entire gene. Since different probe lengths have different effects on hybridization efficiency and signal specificity, the probe length is usually at least 14 base pairs, and the length complementary to the nucleotide sequence of interest is optimally 15-25 base pairs, with the longest length generally not exceeding 30 base pairs. The probe self-complementary sequence is preferably less than 4 base pairs to avoid affecting hybridization efficiency.
In the present invention, a primer refers to a single stranded polynucleotide capable of hybridizing to a nucleic acid and allowing polymerization of the complementary nucleic acid (typically by providing a free 3' -OH group). The primers are capable of achieving specific amplification of the target sequence. Specific amplification refers to amplification of a target sequence by a primer set at a statistically significant level more than a non-target sequence.
Primers or probes of the invention may be chemically synthesized using a phosphoimide solid support method or other well known methods. The nucleic acid sequence may also be modified using a number of means known in the art. Non-limiting examples of such modifications are methylation, capping, substitution with one or more analogs of the natural nucleotide, and modification between nucleotides, for example, modification of uncharged linkers (e.g., methyl phosphate, phosphotriester, phosphoimide, carbamate, etc.), or modification of charged linkers (e.g., phosphorothioate, phosphorodithioate, etc.).
In the present invention, binding agent refers to a naturally occurring or non-naturally occurring molecule that specifically binds to a target. Examples of specific binding agents include, but are not limited to, proteins, peptides, nucleic acids, carbohydrates, and lipids.
In the present invention, a binding agent that specifically binds to a protein encoded by a KIF3A and/or OXCT1 gene, e.g. a receptor for the protein KIF3A and/or OXCT1, a lectin that binds to the protein KIF3A and/or OXCT1, an antibody against the protein KIF3A and/or OXCT1, a peptide antibody (peptabody) against the protein KIF3A and/or OXCT1, a bispecific dual binding agent or a bispecific antibody format. Specific examples of specific binding agents are peptides, peptidomimetics, aptamer, spiegelmer, darpin, ankyrin repeat proteins, kunitz-type domains, antibodies, single domain antibodies and monovalent antibody fragments.
The invention provides a product for diagnosing myocardial infarction, which comprises a reagent for detecting the expression level of KIF3A and/or OXCT1 in a sample; the product comprises a chip, a kit or a nucleic acid membrane strip.
In the present invention, a chip, also referred to as an array, refers to a solid support comprising attached nucleic acid or peptide probes. The array typically comprises a plurality of different nucleic acid or peptide probes attached to the surface of a substrate at different known locations. These arrays, also known as "microarrays," can generally be produced using mechanical synthesis methods or light-guided synthesis methods that combine a combination of photolithographic methods and solid-phase synthesis methods. The array may comprise a planar surface or may be a bead, gel, polymer surface, fiber such as optical fiber, glass or any other suitable nucleic acid or peptide on a substrate. The array may be packaged in a manner that allows for diagnosis or other manipulation of the fully functional device.
The term "microarray" is an ordered arrangement of hybridization array elements, such as polynucleotide probes (e.g., oligonucleotides) or binding agents (e.g., antibodies), on a substrate. The substrate may be a solid substrate, for example, a glass or silica slide, beads, a fiber optic binder, or a semi-solid substrate, for example, a nitrocellulose membrane. The nucleotide sequence may be DNA, RNA or any arrangement thereof.
In the invention, the chip comprises a gene chip and a protein chip; the gene chip comprises a solid phase carrier and an oligonucleotide probe fixed on the solid phase carrier, wherein the oligonucleotide probe comprises an oligonucleotide probe aiming at KIF3A and/or OXCT1 genes and used for detecting the transcription level of the KIF3A and/or OXCT1 genes; the protein chip comprises a solid phase carrier and a specific antibody of KIF3A and/or OXCT1 protein fixed on the solid phase carrier; the gene chip can be used to detect the expression levels of a plurality of genes (e.g., a plurality of genes associated with myocardial infarction) including the human KIF3A and/or OXCT1 genes. The protein chip may be used to detect the expression levels of a plurality of proteins, including human KIF3A and/or OXCT1 protein (e.g., a plurality of proteins associated with myocardial infarction). By simultaneously detecting a plurality of markers related to myocardial infarction, the accuracy of diagnosing myocardial infarction can be greatly improved.
In the present invention, the kit comprises reagents for detecting KIF3A and/or OXCT1 gene or protein, one or more substances selected from the group consisting of: a container, instructions for use, positive control, negative control, buffer, adjuvant, or solvent.
The kit of the invention can be also provided with a kit using instruction, wherein, the instruction describes how to detect by the kit, determine the development of tumor by using the detection result and select the treatment scheme.
The components of the kit may be packaged in aqueous medium or in lyophilized form. Suitable containers in the kit typically include at least one vial, test tube, flask, baud bottle, syringe, or other container in which one component may be placed, and preferably, an appropriate aliquot may be performed. Where more than one component is present in the kit, the kit will also typically contain a second, third or other additional container in which the additional components are placed separately. However, different combinations of components may be contained in one vial. The kits of the invention will also typically include a container for holding the reagents, sealed for commercial sale. Such containers may include injection molded or blow molded plastic containers in which the desired vials may be retained.
The solid support of the kit may be, for example, a plastic, a silicon wafer, a metal, a resin, a glass, a membrane, particles, a precipitate, a gel, a polymer, a sheet, a sphere, a polysaccharide, a capillary, a film, a plate, or a slide. The biological sample may be, for example, a cell culture, a cell line, a tissue, an oral tissue, a gastrointestinal tissue, an organ, a cellular organelle, a biological fluid, a blood sample, a urine sample, or skin.
In an embodiment of the invention, the kit comprises a gene detection kit and a protein immunoassay kit; the gene detection kit comprises reagents for detecting the transcription level of the KIF3A and/or OXCT1 genes; the protein immunoassay kit comprises antibodies specific for KIF3A and/or OXCT1 proteins.
In the present invention, a nucleic acid membrane strip comprises a substrate and an oligonucleotide probe immobilized on the substrate; the substrate may be any substrate suitable for immobilization of oligonucleotide probes including, but not limited to, nylon membranes, nitrocellulose membranes, polypropylene membranes, glass sheets, silica gel wafers, micro magnetic beads.
The chip, kit or nucleic acid membrane strip described in the present invention can be used to detect the expression levels of a plurality of genes or proteins, including KIF3A and/or OXCT1 genes or proteins, and their expression products.
In an embodiment of the invention, the method of screening for a candidate drug for treating myocardial infarction further comprises: the candidate drug obtained in the above step is further tested for the effect of inhibiting myocardial infarction, and if the test compound has a remarkable inhibiting effect on myocardial infarction, the candidate drug is indicated to be the candidate drug for treating myocardial infarction.
Example 1 database analysis
1. Experimental method
1.1 data set preparation
The gene expression profile data was filtered using the keywords "MI (myocardial infarction)" and "Homo sapiens". Inclusion criteria for the dataset were: (1) samples are not less than 5; (2) a control sample is arranged in the data set; the exclusion criteria were: (1) studies at the cell line or animal level; (2) single sample study; (3) repeated or overlapping studies. Final GSE59867, GSE62646, GSE123342 and GSE48060 were included in the study. GSE59867 and GSE62646 were used as experimental groups and GSE123342 and GSE48060 were used as validation groups. All dataset analyses were performed using R software (version 3.5.3).
1.2 differential Gene analysis
After pretreatment of the experimental group data, differential expression analysis was performed using the "llimma" package to obtain the DEGs of MI. The screening criteria for DEGs were set to adj.p.val<0.05，|log 2 FC|>0.4, DEGs visualization with volcanic plot.
2. Experimental results
2.1 data Pre-processing results
The batch effect was removed using the combat function in R-package "sva", respectively. There were 20159 genes in the experimental group and 18439 genes in the validation group (fig. 1).
2.2 differential Gene analysis
389 differential genes were identified in the MI patient group compared to the control group, with a total of 191 genes up-regulated and 198 genes down-regulated (fig. 2).
Analysis revealed that KIF3A and OXCT1 both exhibited significant downregulation in the myocardial infarction group (MI), with an AUC value of 0.784 for KIF3A and 0.843 for OXCT1, and the diagnostic efficacy after combination of the two genes was 0.845 (fig. 3).
Example 2 sample validation
1. Experimental materials
Sample: the laboratory provided 28 human blood samples, 15 of which were control samples, 13 samples of myocardial infarction, and the detailed information is shown in table 1.
Table 1 sample information
Reagent and instrument: RNAliquid overspeed whole blood (liquid sample) total RNA extraction kit, beijing Hui Tian Oriental science and technology Co., ltd; fasteking cDNA first strand synthesis kit, TIANGEN;
SuperReal PreMix Plus (SYBR Green), superreal fluorescent quantitative premix reagent enhancement plate, TIANGEN; centrifuge, centrifuge 5424R; nano-vue Plus,28956057; fluorescent quantitative PCR instrument, gene-9660.
2. Experimental method
2.1 extraction of Total RNA from samples
1) 0.75mL of lysis solution RLS was added to each 0.25mL of blood sample, and the liquid sample was blown with a sample gun to help lyse the cells in the sample.
2) 0.75mL of lysate RLS and 0.25mL of blood sample were added to the EP tube, followed by shaking continuously for 30s with force, mixing, and incubating at 15-30deg.C for 10min to completely decompose nucleoprotein.
3) 0.2mL chloroform was added to each 0.75mL lysate RLS, vigorously shaken for 15s and left at room temperature for 5min.
4) Centrifugation was performed at 12000rpm at 4℃for 10min, RNA was present in the upper aqueous phase, and the aqueous phase was transferred to a new tube for the next operation.
5) 1 time of 70% ethanol by volume is added, and the mixture is inverted and mixed uniformly.
6) Centrifuging at 12000rpm for 45s, discarding the waste liquid, and re-sleeving the adsorption column into the collection tube.
7) 0.5mL deproteinized solution RE was added, centrifuged at 12000rpm for 45s, and the waste solution was discarded.
8) 0.5mL of rinse RW was added, centrifuged at 12000rpm for 45s, and the waste liquid was discarded.
9) 0.5mL of rinse RW was added, centrifuged at 12000rpm for 45s, and the waste liquid was discarded.
10 Placing the adsorption column RA back into the hole collection tube, and centrifuging at 13000rpm for 2min.
11 Taking out the adsorption column RA, placing into an RNase free centrifuge tube, adding 30-50 mu L RNase free water to the middle part of the adsorption membrane according to the expected RNA yield, standing at room temperature for 2min, and centrifuging at 12000rpm for 1min.
2.2 reverse transcription to synthesize mRNA cDNA
mRNA reverse transcription was performed using FastKing cDNA first Strand Synthesis kit (cat# KR 116), genomic DNA reaction was first removed, 5 XgDNA Buffer 2.0. Mu.l, total RNA 1. Mu.g, and RNase Free ddH were added to the tube 2 O was added to a total volume of 10. Mu.l, heated in a water bath at 42℃for 3min, and then 10 XKing RT Buffer 2.0. Mu.l, fastKing RT Enzyme Mix 1.0.0. Mu.l, FQ-RT Primer Mix 2.0. Mu.l, RNase Free ddH was added 2 O5.0. Mu.L, and adding into the above test tube, mixing together to obtain 20. Mu.L, heating at 42deg.C for 15min, heating at 95deg.C for 3min, and storing at-20deg.C or lower.
2.3Real TimePCR
1) The reaction system: amplification was performed using SuperReal PreMix Plus (SYBR Green) (cat# FP 205) and the experimental procedure was carried out according to the product specifications and the Real Time reaction system is shown in Table 2.
TABLE 2Real Time reaction System
2) The amplification procedure was: 95℃for 15min, (95℃for 10sec,55℃for 30sec,72℃for 32 sec). Times.40 cycles, 95℃for 15sec,60℃for 60sec,95℃for 15 sec).
3) Sample realtem PCR detection
2 μl of cDNA of each sample was used as a template after 3-10-fold dilution, and the target gene primer and the internal reference gene primer were used for amplification, respectively.
3. Experimental results
The results showed that the gene expression levels of KIF3A and OXCT1 Myocardial Infarction (MI) in the samples were significantly lower than the control, with a diagnostic potency of 0.826 for KIF3A, 0.795 for OXCT1 and 0.841 for both genes combined (fig. 4).
The above description of the embodiments is only for the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that several improvements and modifications can be made to the present invention without departing from the principle of the invention, and these improvements and modifications will fall within the scope of the claims of the invention.
Claims (10)
1. A system or device for diagnosing myocardial infarction, the system or device comprising:
(1) An acquisition unit: for obtaining expression levels of KIF3A and/or OXCT1 in a sample from a subject;
(2) And a processing unit: obtaining a diagnosis result of myocardial infarction according to the expression condition of the KIF3A and/or the OXCT 1;
preferably, the sample comprises blood, tissue;
preferably, the sample is selected from blood.
2. A computer readable storage medium, characterized in that the storage medium has stored thereon a computer program which, when executed by a processor, implements the system or apparatus of claim 1.
3. A computational model for diagnosing myocardial infarction, the computational model comprising an expression level of input KIF3A and/or OXCT1.
Application of kif3a and/or OXCT1 in constructing a computational model for diagnosing myocardial infarction.
5. An apparatus for diagnosing myocardial infarction, the apparatus comprising a memory for storing program instructions and a processor for invoking the program instructions;
when executed, the program instructions are configured to perform the following:
obtaining data on KIF3A and/or OXCT1 expression levels in a sample from a subject;
and obtaining the diagnosis result of myocardial infarction according to the expression condition of the KIF3A and/or the OXCT1.
6. Use of a reagent for detecting KIF3A and/or OXCT1 expression levels in a sample in the preparation of a product for diagnosing myocardial infarction.
7. The use according to claim 6, wherein the reagent is selected from the group consisting of an oligonucleotide probe specifically recognizing KIF3A and/or OXCT1 genes, a primer specifically amplifying KIF3A and/or OXCT1 genes or a binding agent specifically binding to a protein encoded by KIF3A and/or OXCT1 genes;
preferably, the sample comprises blood, tissue;
preferably, the sample is selected from blood.
8. A product for diagnosing myocardial infarction, comprising an agent that detects the expression level of KIF3A and/or OXCT1 in a sample.
9. The product of claim 8, wherein the product comprises a chip, a kit, or a nucleic acid membrane strip;
preferably, the chip comprises a gene chip comprising an oligonucleotide probe for KIF3A and/or OXCT1 genes for detecting the transcription level of KIF3A and/or OXCT1 genes, a protein chip comprising a specific binding agent for KIF3A and/or OXCT1 proteins; the kit comprises a gene detection kit and a protein detection kit, wherein the gene detection kit comprises a reagent or a chip for detecting the transcription level of the KIF3A and/or the OXCT1 genes, and the protein detection kit comprises a reagent or a chip for detecting the expression level of the KIF3A and/or the OXCT1 proteins;
preferably, the kit comprises reagents for detecting the expression level of KIF3A and/or OXCT1 genes or proteins by RT-PCR, biochip detection, southern blotting, in situ hybridization, immunoblotting, mass spectrometry;
preferably, the sample comprises blood, tissue;
preferably, the sample is selected from blood.
Use of kif3a and/or OXCT1 in screening candidate drugs for the treatment of myocardial infarction;
preferably, the method for screening candidate drugs for treating myocardial infarction comprises the following steps: treating a culture system expressing or containing KIF3A and/or OXCT1 genes or proteins encoded thereby with a substance to be screened; and detecting expression or activity of KIF3A and/or OXCT1 gene or a protein encoded thereby in the system; wherein the substance to be screened is a candidate drug for treating myocardial infarction when the substance to be screened promotes the expression level or activity of KIF3A and/or OXCT1 gene or a protein encoded thereby.
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