CN108018349A - With the relevant excretion body molecular marker of active tuberculosis - Google Patents
With the relevant excretion body molecular marker of active tuberculosis Download PDFInfo
- Publication number
- CN108018349A CN108018349A CN201710422881.XA CN201710422881A CN108018349A CN 108018349 A CN108018349 A CN 108018349A CN 201710422881 A CN201710422881 A CN 201710422881A CN 108018349 A CN108018349 A CN 108018349A
- Authority
- CN
- China
- Prior art keywords
- genes
- active tuberculosis
- tuberculosis patient
- examination
- rfpl3s
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- 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
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
- G01N33/5695—Mycobacteria
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/60—Complex ways of combining multiple protein biomarkers for diagnosis
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses with the relevant excretion body molecular marker of active tuberculosis.Molecular marker disclosed by the invention --- RFPL3S,ENO4,NTS,ZNF705A,POSTN,RBM11,TSEN15,MMRN1,PWP1,TRHDE,PRKX,ERCC8,EFCAB7,GDAP1,SLC9B1,FMO1,MTRNR2L6,ALDH1L2,BNIP2,AGAP4,C18orf21,TIMM9,SLC17A2,HMMR,OR5B17,OFCC1,POC5,SLC4A7,MTM1,CLU,FAR1,MGAT4A,ADH1C,RNF7,VNN2,PARD3,NR1H4,ME2,ACSL4 and SLC16A7 genes,Available for diagnostic activities tuberculosis.
Description
Technical field
The present invention relates in biological technical field, with the relevant excretion body molecular marker of active tuberculosis.
Background technology
The goldstandard of diagnosis of tuberculosis is bacteriology Sputum smears microscopy and Sputum culturing at present, but bacteriological detection sensitivity
Low, time-consuming, is unfavorable for each phase diagnosis of tuberculosis and treatment.Tuberculosis Susceptible population such as children, often because expectoration can not be coordinated,
Sputum specimen collection is difficult, and bacteriological detection limitation is more obvious.It is very necessary to find other diagnosis samples in addition to phlegm,
Such as the blood easily gathered.Serum and plasma fraction are complicated, and really specific markers are probably micro, this leads
Cause the effect for screening tuberculosis specific markers from serum or blood plasma unsatisfactory.Excretion body is cell active secretion
, the lipid bilayer vesicle sample corpusculum that size is 30-120nm, can selectively wrap up protein, nucleic acid and lipid, participate in cell
Between matter transportation and signal transmission.They are widely present in the various body fluid of organism, including blood, urine, ascites, sheep
Water, milk, cerebrospinal fluid, BAL fluid etc. (Th é ry, 2011).Component is simple in excretion body, carries cell and is working as
When physiological condition under specific information.
The content of the invention
The technical problems to be solved by the invention be how examination active tuberculosis patient (Active
tuberculosis,ATB)。
Present invention firstly provides following applications 1) or 2)：
1) system the answering in preparing examination or aiding in examination active tuberculosis patient product of G1 expressions is detected
With；The G1 is RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes, TSEN15
Gene, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 genes,
SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21 bases
Cause, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
2) application of the system of the G1 expressions in examination or auxiliary examination active tuberculosis patient is detected.
In above application, the system of the detection G1 expressions can be the reagent detected needed for the G1 expressions
And/or instrument.
In above application, the system of the detection G1 expressions can be to detect the G1 using method of the prior art
Reagent and/or instrument needed for expression, reagent as described in using high-flux sequence detection needed for G1 expressions and/or
Instrument, or reagent and/or instrument needed for using G1 expressions described in quantitative PCR detection, or utilize northern hybridization skills
Art detects the reagent and/or instrument needed for the G1 expressions, or using needed for G1 expressions described in genechip detection
Reagent and/or instrument.
In above application, the high-flux sequence can utilize Illumina microarray datasets (such as Illumina
HiseqTM2500) carry out.
In above application, the system of the detection G1 expressions may also include data handling system, the data processing
System is used for analyzing that method of the prior art directly obtains as a result, determining the expression of the G1.The data processing
System can be software and/or module.
Present invention also offers following M1) or application M2)：
M1 application of the system of P1 contents in preparing examination or aiding in examination active tuberculosis patient product) is detected；
M2 application of the system of the P1 contents in examination or auxiliary examination active tuberculosis patient) is detected；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE,
PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、
TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、
VNN2, PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
In above application, the system of the detection P1 contents can be to detect the P1 contents using method of the prior art
Required reagent and/or instrument, reagent and/or instrument as described in using mass spectrum or the detection of its correlation technique needed for P1 contents,
Or reagent and/or instrument needed for using P1 contents described in immuning hybridization technology for detection, or detect the P1 using elisa technique
Reagent and/or instrument needed for content, or reagent and/or instrument needed for using protein chip or the test paper detection P1 contents
Device.
Present invention also offers following N1)-N4) in any application：
N1 the examination of active tuberculosis Patient labels' thing or auxiliary examination active tuberculosis patient method) are used as using G1
In used system in following a1) or a2) in application：
A1 examination or auxiliary examination active tuberculosis patient product) are prepared；
A2) examination or auxiliary examination active tuberculosis patient；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
N2 the examination of active tuberculosis Patient labels' thing or auxiliary examination active tuberculosis patient method) are used as using P1
In used system in above-mentioned a1) or a2) in application；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE,
PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、
TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、
VNN2, PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein；
N3) using the G1 as active tuberculosis Patient labels thing in above-mentioned a1) or a2) in application；
N4) using the P1 as active tuberculosis patient in above-mentioned a1) or a2) in application.
It is described that the examination of active tuberculosis Patient labels' thing or auxiliary examination active tuberculosis patient side are used as using G1
System used can be the system of detection G1 expressions described above in method.
Present invention also offers following X1) or product X2)：
X1) examination or auxiliary examination active tuberculosis patient product, to detect the system of G1 expressions；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
X2) examination or auxiliary examination active tuberculosis patient product, to detect the system of P1 contents；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE,
PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、
TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、
VNN2, PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
Present invention also offers the construction method that the active tuberculosis patient relevant molecular characteristics of non-diagnostic purpose are composed, institute
The method of stating includes：The RNA or protein in blood are organized to active tuberculosis patient group and inactive tuberculosis patient respectively
Quantitative analysis is carried out, active tuberculosis patient relevant molecular characteristics spectrum is obtained according to analysis result；The active tuberculosis
Patient's relevant molecular characteristics spectrum is G1 or P1；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE,
PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、
TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、
VNN2, PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
It is described that active tuberculosis patient group and inactive tuberculosis patient are organized in blood respectively in the above method
RNA or protein carry out quantitative analysis concretely respectively to active tuberculosis patient group and inactive tuberculosis patient's group
RNA or protein in blood excretion body carry out quantitative analysis.
In the above method, the RNA organized to active tuberculosis patient group and inactive tuberculosis patient in blood
Or protein carries out quantitative analysis and specifically may also include：Purify active tuberculosis patient group and inactive tuberculosis patient's group
RNA or protein in blood, the content of RNA or protein is detected using Illumina microarray datasets.
The purifying active tuberculosis patient group can with the RNA in inactive tuberculosis patient group blood or protein
Carried out using the magnetic bead with Oligo (dT).
In the above method, the active tuberculosis patient group may include at least one active tuberculosis patient.It is described
Inactive tuberculosis patient's group may include at least one inactive tuberculosis patient.
In the present invention, the examination or auxiliary examination active tuberculosis patient product can be examination or auxiliary examination activity
Property it is lungy medicine and/or health equipment, such as reagent, test paper, material or instrument.
In the present invention, the G1 expressions can be the expression of G1 described in blood；The P1 contents can be blood
Described in P1 content.The expression of the G1 expressions concretely G1 described in blood excretion body；The P1 contents
The concretely content of P1 described in blood excretion body.
In practical applications, can by compare RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15,
MMRN1、PWP1、TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、
AGAP4、C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、
MGAT4A, ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7 are in object to be measured and inactive tuberculosis
Expression in patient's serum excretion body judges whether object to be measured is active tuberculosis patient.
Specifically, criterion can be：As RFPL3S, ENO4 of object to be measured, NTS, ZNF705A, POSTN, RBM11,
TSEN15、MMRN1、PWP1、TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、
BNIP2、AGAP4、C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、
At least one in this 40 genes of FAR1, MGAT4A, ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7
A expression is higher than 2 times of inactive tuberculosis patient corresponding gene, and the object to be measured is or candidate is activity knot
Core patient, such as RFPL3S, ENO4 of object to be measured, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1,
TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、
C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、
The expression of this 40 genes of ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7 is not higher than non-live
2 times of dynamic property tuberculosis patient corresponding gene, the object to be measured is or candidate is inactive tuberculosis patient.Criterion
Or：As RFPL3S, ENO4 of object to be measured, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1,
TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、
C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、
The expression of at least one in this 40 genes of ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7
It is significantly higher than inactive tuberculosis patient's corresponding gene, the object to be measured is or candidate is active tuberculosis patient, such as
RFPL3S, ENO4 of object to be measured, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE, PRKX,
ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、
SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、
The expression of this 40 genes of PARD3, NR1H4, ME2, ACSL4, SLC16A7 is not significantly higher than inactive tuberculosis sufferer
Person's corresponding gene, the object to be measured is or candidate is inactive tuberculosis patient.
In the present invention, the inactive tuberculosis patient can be Healthy People or/and tuberculosis latent infection person.
The present invention is by comparing inactive tuberculosis patient (Healthy People and tuberculosis latent infection person) and active tuberculosis
The difference expression gene of patient, and by analysis, find and the relevant differential expression molecule of active tuberculosis ---
RFPL3S、ENO4、NTS、ZNF705A、POSTN、RBM11、TSEN15、MMRN1、PWP1、TRHDE、PRKX、ERCC8、
EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、SLC17A2、
HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、PARD3、
NR1H4, ME2, ACSL4, SLC16A7, and this 40 molecules in active tuberculosis patient relative to inactive tuberculosis
Expression quantity increase in patient, shows that this 40 molecules can be used as biomolecule to identify, for active tuberculosis patient's
Clinical diagnosis.
Brief description of the drawings
Fig. 1 characterizes for serum excretion volume morphing.
Fig. 2 is Healthy People (HC), tuberculosis latent infection crowd (LTBI) and active tuberculosis patient (ATB) differential expression
Gene thermal map.Dotted line represents notable cance high-expression gene cut-off rule.
Fig. 3 is Healthy People (HC), tuberculosis latent infection crowd (LTBI) and active tuberculosis patient (ATB) differential gene
Expression pattern.Caption：N represents number gene, LMH represent it is low-in-height mode, LHM represents low-high-middle pattern, and MHL is represented
In-height-low mode, HML represents Gao-medium-low pattern, and MLH represents medium-low-height mode, and HLM represents Gao-low-middle pattern.
Fig. 4 is preceding 20 genes of tuberculosis latent infection person (LTBI) significantly high expression in both modes.Caption：LHM
Low-high-middle pattern is represented, in MHL representatives-height-low mode.Red mark gene represents base of the functional clustering in " cell cycle "
Cause, blueness mark gene represent with reported " mitochondrial function abnormal " relevant gene (Lee et al., 2009；Behar
et al.,2011)。
Fig. 5 is preceding 20 genes of active tuberculosis patient (ATB) significantly high expression in both modes.Caption：LMH
Represent it is low-in-height mode, MLH represents medium-low-height mode.Red mark gene represents the gene consistent with having reported result
(Pacis et al.,2015)。
Embodiment
The present invention is further described in detail with reference to embodiment, the embodiment provided is only for explaining
The bright present invention, the scope being not intended to be limiting of the invention.Experimental method in following embodiments, unless otherwise specified, is
Conventional method.Material used, reagent, instrument etc., are commercially available unless otherwise specified in following embodiments.
Quantitative test in following embodiments, is respectively provided with three repeated experiments, and results are averaged.
Embodiment 1 and active tuberculosis patient and the relevant molecular marker of tuberculosis latent infection person
The present embodiment is with active tuberculosis patient (Active tuberculosis, ATB), tuberculosis latent infection person
(Latent tuberculosis infection, LTBI) and healthy population (HC) serum excretion body are research object, extract blood
Clear excretion body total serum IgE, is sequenced using RNA-seq technologies, and bioinformatic analysis screens to obtain the RNA of group difference expression
Molecule.
Experiment sample used in this experiment follows the morals mark of Declaration of Helsinki (Helsinki Declaration)
Standard, meets Medicine Ethics specification, has passed through attached Ethics Committee of BJ Chest Science Hospital of the Capital University of Medical Sciences and has examined, and all
Subject endorsed informed consent form.
Healthy People, tuberculosis latent infection crowd, totally 90, active tuberculosis patients serum sample are collected, per middle type 30
Example, with 15 serum samples, 1ml/, is mixed into 1 sample cell (pool), every group of 2 sample cells.Details are shown in Table 1.
Sample inclusive criteria：
Healthy People meets following four condition at the same time：1) tuberculin skin test (TST) scleroma diameter<5mm；2) interferon
Release test (IGRA) detection is negative；3) no active tuberculosis and other diseases medical history；4) chest film inspection is without exception.
Tuberculosis latent infection person meets following four condition at the same time：1) tuberculin skin test (TST) scleroma diameter>10mm；
2) interferon release test (IGRA) detection is positive；3) no active tuberculosis and other diseases medical history；4) chest film inspection is no different
Often.
Active tuberculosis patient meets following three conditions at the same time：1) there is tuberculosis symptom；2) chest x-ray has
Tuberculosis；3) continuously (+) or the culture of phlegm mycobacterium tuberculosis are positive at least twice for phlegm collection bacterium.
Concrete operation step is as follows：
1. excretion body separates and RNA extractions：The above-mentioned sample cell 1000g mixed is centrifuged into 15min, removes cellular component
And fragment.Supernatant 16 is taken, 4 DEG C of centrifugation 30min of 500g, supernatant removes big film bubble component with 0.22 μm of membrane filtration and albumen is answered
Compound.120,000g 4 DEG C of ultracentrifugation 3h, abandon supernatant, blot supernatant as far as possible, centrifuge tube is tipped upside down on blotting paper and is drained
Liquid on tube wall, obtains excretion body.
Excretion body sample is carried out respectively using transmission electron microscope and NanoSight NS300 particle trace analysis instrument
Form and particle diameter distribution detection, as a result (Fig. 1) display：The rounded imitated vesicle structure of excretion body of all samples, size is homogeneous, diameter
About 100nm (shown in white arrow), the particle diameter peak value of HC, LTBI and ATB are respectively 95nm, 91nm and 117nm.
2. it is directly added into RNAiso Plus reagent (Takara, article No. in being precipitated to excretion body：9108), said according to reagent
Bright book extracts total serum IgE.Brief step is as follows：Suitable RNAiso Plus reagents are added in sample, are mixed, room temperature places 5min,
Centrifuging and taking supernatant, adds the chloroform of 0.2 times of volume, and vibration mixes, and room temperature places 5min, and 12,000g 4 DEG C of centrifugation 15min, inhale
The isopropanol of 0.5-1 times of volume is added in the supernatant taken, overturns and mixes, room temperature places 10min, and supernatant, 75% ethanol are abandoned in centrifugation
Precipitation, super-clean bench drying residual ethanol are washed, cell RNA is dissolved in 50 μ l DEPC water, and excretion body RNA is dissolved in as far as possible few
In DEPC water, to obtain the excretion body RNA for high concentration of trying one's best.1% agarose gel electrophoresis analyzes RNA purity and integrality,
2100 accurate quantifications of Agilent simultaneously detect RNA distribution of lengths situations.
3.RNA is sequenced and data analysis：Meet the RNA of quality inspection requirement by RNA library construction Kits (
UltraTM RNA Library Prep Kit, NEB) transcript profile cDNA library of the structure for the sequencing of two generations.Use sequenator
Illumina HiseqTM 2500 carry out RNA-seq sequencings.Obtained primitive sequencer sequence is sequenced, uses software FASTX-
Toolkit (version 0.0.13.2) is filtered, and is removed joint sequence and low quality reads, is removed using fastx_clipper
Joint sequence, removes low quality base (Q using fastq_quality_trimmer from end<20), if the length of reads
Directly reads is filtered out less than 30.Retain q values using fastq_quality_filter and be more than 20, p value is more than 70
reads.Finally obtain clean reads.Clean after different samples are filtered using software Tophat (version 2 .0.9)
Reads is navigated on hg38 genomes.The reads matched further passes through software Cufflinks (version 2 .2.1)
(Trapnell et al., 2010) carries out assembling splicing, and arrange parameter "-M " is matched on rRNA with filtering out those
Reads.FPKM (fragments per are passed through to the reads uniquely positioned using software cuffdiff (version 2 .0.0)
Kilobase per million reads) quantitative gene expression, and difference expression gene between more different samples are carried out, it is poor
The cluster thermal map of different expressing gene is drawn by software pheatmap (R softwares).
1. sequencing data essential information of table
Note：1：Sample cell 1,2：Sample cell 2.* biology repetition is represented.
4. result
By the way that sequencing data to be compared to the reference gene group (hg38) to people, the base of three groups of crowd's serum excretion bodies has been obtained
Because of express spectra, identified respectively in Healthy People (HC), latent infection crowd (LTBI) and active tuberculosis patient (ATB)
44187,43428 and 44261 genes, wherein it is encoding gene (table 1) to have 18913,18882 and 18926 respectively.In order to obtain
The differential expression spectrum of three groups of samples is obtained, three groups of sample serum excretion body transcript profile data are carried out with comparison analysis two-by-two, and (difference is again
Number >=2, p value<0.05) and thermal map (Fig. 2) is drawn.The results show：Healthy People (HC), tuberculosis latent infection person (LTBI) and activity
Property tuberculosis patient (ATB) serum excretion body express spectra has significant difference, compared with LTBI and ATB, 1188 in HC group samples
The high expression of a gene conspicuousness, compared with HC and ATB, there is 1020 notable cance high-expression genes in LTBI group samples, and and LTBI
Compared with HC, there are 681 genes that there is the high expression of conspicuousness in ATB group samples.
Classify to three groups of sample serum excretion body transcriptome differences genes, be finally divided into six major class expression patterns (figure
, including low 3)-in-high (LMH) pattern, it is low-high-in (LHM) pattern, in-high-low (MHL) pattern, high-medium-low (HML) mould
Formula, medium-low-high (MLH) pattern and height-low-in (HLM) pattern.Filter out in each pattern 20 before conspicuousness ranking
The gene (Fig. 4, Fig. 5) of the high expression of conspicuousness, can be used as potential tuberculosis in difference expression gene, especially LTBI, ATB group
Disease diagnosis molecule marker.
Tuberculosis latent infection crowd (LTBI) serum excretion body specificity overexpression gene, it is low-high-in (LHM) pattern
In have：MT-ND3、RINT1、UBE2S、COX11、MDM2、AP1AR、LIPF、GLOD4、TMOD2、ZNF684、MACC1、PA2G4、
PUDP、DMXL1、SPTLC2、WDR70、GPR6、DROSHA、ABCF2、ZNF778；In-high-low (MHL) pattern in have：
ST6GALNAC2、TTLL10、ABCC8、PCSK1N、GPX4、ZDHHC2、TLR7、MT-CO3、LOR、GMPR2、CHM、SLC35A1、
MT-CO1, MARCH6, TADA1, C19orf48, KRTAP9-1, POP7, TDP2, VSIG1, are shown in Table 2, these gene tuberculosis are hidden
Expression quantity in infection population is all remarkably higher than table of the corresponding gene in Healthy People (HC) and active tuberculosis patient (ATB)
Up to amount, show that these genes can be used as the molecular marker of tuberculosis latent infection to be used for the examination of tuberculosis latent infection person.
Table 2, the relevant molecular marker of tuberculosis latent infection
Note：40 are listed in table 2 in tuberculosis latent infection person relative to non-tuberculosis latent infection person (Healthy People and work
Dynamic property tuberculosis patient) in expression there is the cance high-expression gene of significant difference.
In practical applications, can by compare MT-ND3, RINT1, UBE2S, COX11, MDM2, AP1AR, LIPF,
GLOD4、TMOD2、ZNF684、MACC1、PA2G4、PUDP、DMXL1、SPTLC2、WDR70、GPR6、DROSHA、ABCF2、
ZNF778、ST6GALNAC2、TTLL10、ABCC8、PCSK1N、GPX4、ZDHHC2、TLR7、MT-CO3、LOR、GMPR2、CHM、
SLC35A1, MT-CO1, MARCH6, TADA1, C19orf48, KRTAP9-1, POP7, TDP2, VSIG1 are in object to be measured and non-knot
Expression in core latent infection person (Healthy People and active tuberculosis patient) serum excretion body is to judge object to be measured
No is tuberculosis latent infection person.Specifically, the criterion obtained according to the above results is as follows：Such as MT-ND3 of object to be measured,
RINT1、UBE2S、COX11、MDM2、AP1AR、LIPF、GLOD4、TMOD2、ZNF684、MACC1、PA2G4、PUDP、DMXL1、
SPTLC2、WDR70、GPR6、DROSHA、ABCF2、ZNF778、ST6GALNAC2、TTLL10、ABCC8、PCSK1N、GPX4、
ZDHHC2、TLR7、MT-CO3、LOR、GMPR2、CHM、SLC35A1、MT-CO1、MARCH6、TADA1、C19orf48、KRTAP9-
1st, the expression of at least one is higher than non-tuberculosis latent infection person's (Healthy People in this 40 genes of POP7, TDP2, VSIG1
With active tuberculosis patient) 2 times of corresponding gene, the MT- of the doubtful tuberculosis latent infection person of object to be measured, such as object to be measured
ND3、RINT1、UBE2S、COX11、MDM2、AP1AR、LIPF、GLOD4、TMOD2、ZNF684、MACC1、PA2G4、PUDP、
DMXL1、SPTLC2、WDR70、GPR6、DROSHA、ABCF2、ZNF778、ST6GALNAC2、TTLL10、ABCC8、PCSK1N、
GPX4、ZDHHC2、TLR7、MT-CO3、LOR、GMPR2、CHM、SLC35A1、MT-CO1、MARCH6、TADA1、C19orf48、
The expression of this 40 genes of KRTAP9-1, POP7, TDP2, VSIG1 not higher than non-tuberculosis latent infection person (Healthy People and
Active tuberculosis patient) 2 times of corresponding gene, which is non-tuberculosis latent infection person.
Active tuberculosis patient (ATB) serum excretion body specificity overexpression gene, it is low-in-high (LMH) pattern in
Have：RFPL3S、ENO4、NTS、ZNF705A、POSTN、RBM11、TSEN15、MMRN1、PWP1、TRHDE、PRKX、ERCC8、
EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4；In medium-low-high (MLH) pattern
Have：C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、
ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7, are shown in Table 3, these Gene Activity tuberculosis patients
In expression quantity be all remarkably higher than expression quantity of the corresponding gene in Healthy People and tuberculosis latent infection crowd, show these genes
It can be used for the examination of active tuberculosis patient as the molecular marker of active tuberculosis.
The relevant molecular marker of table 3, active tuberculosis
Note：40 are listed in table 3 in active tuberculosis patient relative to inactive tuberculosis patient's (Healthy People
With tuberculosis latent infection person) in the expression cance high-expression gene that there were significant differences.
In practical applications, can by compare RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15,
MMRN1、PWP1、TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、
AGAP4、C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、
MGAT4A, ADH1C, RNF7, VNN2, PARD3, NR1H4, ME2, ACSL4, SLC16A7 are in object to be measured and inactive tuberculosis
Expression in patient (Healthy People and tuberculosis latent infection person) serum excretion body judges whether object to be measured is activity
Property tuberculosis patient.Specifically, the criterion obtained according to the above results is as follows：Such as RFPL3S, ENO4 of object to be measured,
NTS、ZNF705A、POSTN、RBM11、TSEN15、MMRN1、PWP1、TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、
SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、
OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、PARD3、NR1H4、ME2、ACSL4、
The expression of at least one higher than inactive tuberculosis patient, (dive by Healthy People and tuberculosis in this 40 genes of SLC16A7
Lie prostrate the infected) 2 times of corresponding gene, the doubtful active tuberculosis patient of object to be measured, such as RFPL3S of object to be measured,
ENO4、NTS、ZNF705A、POSTN、RBM11、TSEN15、MMRN1、PWP1、TRHDE、PRKX、ERCC8、EFCAB7、GDAP1、
SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、SLC17A2、HMMR、OR5B17、
OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、PARD3、NR1H4、ME2、ACSL4、
The expression of this 40 genes of SLC16A7 is not higher than inactive tuberculosis patient (Healthy People and tuberculosis latent infection person)
2 times of corresponding gene, the object to be measured are inactive tuberculosis patient.
Claims (10)
1. detect application of the system of G1 expressions in preparing examination or aiding in examination active tuberculosis patient product；Institute
State G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes, TSEN15 genes,
MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 genes, SLC9B1 bases
Cause, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21 genes, TIMM9 bases
Cause, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes, MTM1 genes, CLU
Gene, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes, NR1H4 genes, ME2
Gene, ACSL4 genes and/or SLC16A7 genes.
2. detect application of the system of G1 expressions in examination or auxiliary examination active tuberculosis patient；The G1 is
RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes, TSEN15 genes, MMRN1
Gene, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 genes, SLC9B1 genes,
FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21 genes, TIMM9 genes,
SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes, MTM1 genes, CLU bases
Cause, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes, NR1H4 genes, ME2 bases
Cause, ACSL4 genes and/or SLC16A7 genes.
3. application according to claim 1 or 2, it is characterised in that：The system of the detection G1 expressions is detection institute
State the reagent and/or instrument needed for G1 expressions.
4. following M1) or application M2)：
M1 application of the system of P1 contents in preparing examination or aiding in examination active tuberculosis patient product) is detected；
M2 application of the system of the P1 contents in examination or auxiliary examination active tuberculosis patient) is detected；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE, PRKX,
ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、
SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、
PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
5. application according to claim 4, it is characterised in that：The system for detecting the P1 contents is the detection P1 contents
Required reagent and/or instrument.
6. following N1)-N4) in any application：
N1 institute in the examination of active tuberculosis Patient labels' thing or auxiliary examination active tuberculosis patient method) is used as using G1
System is in following a1) or a2) in application：
A1 examination or auxiliary examination active tuberculosis patient product) are prepared；
A2) examination or auxiliary examination active tuberculosis patient；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
N2 institute in the examination of active tuberculosis Patient labels' thing or auxiliary examination active tuberculosis patient method) is used as using P1
System is in above-mentioned a1) or a2) in application；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE, PRKX,
ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、
SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、
PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein；
N3) using the G1 as active tuberculosis Patient labels thing in above-mentioned a1) or a2) in application；
N4) using the P1 as active tuberculosis patient in above-mentioned a1) or a2) in application.
7. following X1) or product X2)：
X1) examination or auxiliary examination active tuberculosis patient product, to detect the system of G1 expressions；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
X2) examination or auxiliary examination active tuberculosis patient product, to detect the system of P1 contents；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE, PRKX,
ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、
SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、
PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
8. according to product described in any application in claim 1-6 or claim 7, it is characterised in that：The G1 expression
Level is the expression of G1 described in blood；The P1 contents are the content of P1 described in blood.
9. application according to claim 8 or product, it is characterised in that：The G1 expressions are institute in blood excretion body
State the expression of G1；The P1 contents are the content of P1 described in blood excretion body.
10. the construction method of active tuberculosis patient relevant molecular characteristics spectrum, including：Respectively to active tuberculosis patient's group
RNA or the protein progress quantitative analysis in blood are organized with inactive tuberculosis patient, activity is obtained according to analysis result
Tuberculosis patient relevant molecular characteristics are composed；The active tuberculosis patient relevant molecular characteristics spectrum is G1 or P1；
The G1 for RFPL3S genes, ENO4 genes, NTS genes, ZNF705A genes, POSTN genes, RBM11 genes,
TSEN15 genes, MMRN1 genes, PWP1 genes, TRHDE genes, PRKX genes, ERCC8 genes, EFCAB7 genes, GDAP1 bases
Cause, SLC9B1 genes, FMO1 genes, MTRNR2L6 genes, ALDH1L2 genes, BNIP2 genes, AGAP4 genes, C18orf21
Gene, TIMM9 genes, SLC17A2 genes, HMMR genes, OR5B17 genes, OFCC1 genes, POC5 genes, SLC4A7 genes,
MTM1 genes, CLU genes, FAR1 genes, MGAT4A genes, ADH1C genes, RNF7 genes, VNN2 genes, PARD3 genes,
NR1H4 genes, ME2 genes, ACSL4 genes and/or SLC16A7 genes；
The P1 for RFPL3S, ENO4, NTS, ZNF705A, POSTN, RBM11, TSEN15, MMRN1, PWP1, TRHDE, PRKX,
ERCC8、EFCAB7、GDAP1、SLC9B1、FMO1、MTRNR2L6、ALDH1L2、BNIP2、AGAP4、C18orf21、TIMM9、
SLC17A2、HMMR、OR5B17、OFCC1、POC5、SLC4A7、MTM1、CLU、FAR1、MGAT4A、ADH1C、RNF7、VNN2、
PARD3, NR1H4, ME2, ACSL4 and/or SLC16A7 protein.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710422881.XA CN108018349A (en) | 2017-06-07 | 2017-06-07 | With the relevant excretion body molecular marker of active tuberculosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710422881.XA CN108018349A (en) | 2017-06-07 | 2017-06-07 | With the relevant excretion body molecular marker of active tuberculosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108018349A true CN108018349A (en) | 2018-05-11 |
Family
ID=62079241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710422881.XA Pending CN108018349A (en) | 2017-06-07 | 2017-06-07 | With the relevant excretion body molecular marker of active tuberculosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108018349A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109825575A (en) * | 2019-04-08 | 2019-05-31 | 首都医科大学附属北京胸科医院 | Auxiliary diagnosis miRNA marker lungy and its application |
| CN115856300A (en) * | 2022-08-01 | 2023-03-28 | 南京大学 | Lung cancer-related plasma exosome protein marker, antibody and application thereof |
-
2017
- 2017-06-07 CN CN201710422881.XA patent/CN108018349A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109825575A (en) * | 2019-04-08 | 2019-05-31 | 首都医科大学附属北京胸科医院 | Auxiliary diagnosis miRNA marker lungy and its application |
| CN115856300A (en) * | 2022-08-01 | 2023-03-28 | 南京大学 | Lung cancer-related plasma exosome protein marker, antibody and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tay et al. | Advances in microfluidics in combating infectious diseases | |
| TW201718874A (en) | Single-molecule sequencing of plasma DNA | |
| CN103080336A (en) | Kits, devices and methods for detecting chromosome copy number of embryo or tumor | |
| WO2019223502A1 (en) | Method for detecting pathogens based on cfdna high-throughput sequencing | |
| CN109825575A (en) | Auxiliary diagnosis miRNA marker lungy and its application | |
| CN110205378A (en) | One group of tuberculosis of spine blood plasma miRNA Combining diagnosis marker and its application | |
| US11493412B2 (en) | Method and kit for exosomes and associated biomacromolecules capture | |
| CN108018349A (en) | With the relevant excretion body molecular marker of active tuberculosis | |
| CN106591313A (en) | Ovarian mucinous cancer cell 3AO nucleate aptamer WYZ-1 and screening method and application thereof | |
| ElShelmani et al. | Differential circulating MicroRNA expression in age-related macular degeneration | |
| Guo et al. | Extracellular vesicles and their diagnostic and prognostic potential in cancer | |
| CN113637668A (en) | Kit for simultaneously extracting pathogenic bacteria DNA of blood plasma and blood cells and application thereof | |
| CN108018350A (en) | With the relevant excretion body molecular marker of tuberculosis latent infection | |
| JP3169027U (en) | Gene population detection structure | |
| WO2017092483A1 (en) | Kit for diagnosing tuberculosis through detecting free nucleic acid and use thereof | |
| US20210363601A1 (en) | Test to distinguish viral-only from bacterial infection or viral/bacterial coinfection using a respiratory swab | |
| CA3232274A1 (en) | Drain fluid for diagnostics | |
| Slowey | Salivary diagnostics using purified nucleic acids | |
| WO2017173698A1 (en) | Molecular marker and primer pair for diagnosing mycobacterium tuberculosis infection and uses thereof | |
| WO2016185564A1 (en) | Fractionation method and method for fractionation and acquisition of extracellular vesicles | |
| CN115992220B (en) | Molecular marker for rheumatoid arthritis and application thereof | |
| CN111349698A (en) | Excretor-in-vivo nucleic acid marker related to central nervous system infection diseases and application thereof | |
| Coppée et al. | 5WBF: a low-cost and straightforward whole blood filtration method suitable for whole-genome sequencing of Plasmodium falciparum clinical isolates | |
| CN110736834A (en) | Method, device and system for screening and diagnosing liver cancer based on high-throughput sequencing method | |
| US20180245167A1 (en) | Method for evaluation of viability of viruses with lymphotropism properties |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180511 |