CN107058521A - A kind of detecting system for detecting human immunity state - Google Patents
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Abstract
The present invention relates to a kind of detecting system for detecting human immunity state, belong to technical field of gene detection, IFI27 in the detecting system human peripheral blood of the present invention, ISG15, IFI44L, RSAD2, HERC5, IFITM3, IFI44, IFIT3, EPSTI1, IFIT1, HP, ANXA3, ARG1, FCGR1B, S100A12, MMP9, IL18R1, TLR5, GYG1, totally 20 genes are detected FCGR1A, the assessment to human immunity state is reached by the up-regulation or decline of each gene expression amount, and and then instruct accurate medical treatment using these genes, including the accurate parting of disease, prognosis, treatment tracking and therapeutic evaluation, with excellent clinical value, application prospect is good.
Description
Technical field
The present invention relates to technical field of gene detection, in particular it relates to it is a kind of by detect the expression quantity of target gene come
Evaluate the detecting system of human body immune state.
Background technology
Immune response is that human body is invaded inoculating microbe and the abnormal physiological reaction of endogenous body, shows activation or presses down
Some biological pathways are made, therefore the exception of human immunity state can indicate that human body is had by inoculating microbe invasion or body
The lesions such as cancer.Detect that the most frequently used technological means of human immune system's state is blood count, such as it is certain type of white
Cell quantity.Also there is the quantitative detection to indivedual immune-related proteins in serum.
Either blood count, or the detection of immune-related protein amount, all can only general orientation instruction immune disorder.Now
Accurate medical treatment have higher requirement, it is necessary to be detected to important molecular pathway to the detection of immune state, in favor of
The accurate parting of disease.
Peripheral blood is widely used in the discovery of biomarker as a kind of detection method in minimally invasive source.In document
Some different methods were reported, for example：The problem of anaphylactic shock (septic shock) is classified.There is document report to cross to use
The method of machine learning is clustered to the differential gene of three kinds of hypotypes of anaphylactic shock.However, for the method for machine learning,
If can not effectively use, it is easy to the phenomenon of over-fitting occur.It generally all can use to supervise in machine learning in research and learn
The method of habit, research is carried out in multiple data sets, and a portion data are used to build model, and another part data are used
In checking.In one is studied, in this way, find 11 genes in infection inflammation (Infectious
Inflammation in the parting that aseptic inflammation (Sterile Inflammation) is distinguished in), work well.Another
The method for improving repeatability is to abandon to use genes of individuals, then uses genetic model.This method is in systemic red yabbi
It is proved to have good effect in sore (Systemic Lupus Erythematosus, SLE) and some Other diseases.
In order to find biomarker from individual disease, applicant's guess can be observed in wider disease class
The feedback of immune system.Extensive disease type, which refers to, is not limited to infection immunity class disease.In fact, the dysfunction of immune system
It is found in a variety of disease types including being lacked of proper care including cranial nerve etc..The disorder of some immune systems may be lost with gene
The mode of tune is reacted in peripheral blood.The potential mechanism gone out disclosed in the gene imbalance possibility shown in many diseases is i.e.
It is immune response.In addition, applicant has great potential clinical practice interested discovery.Clinical practice includes disease
The many aspects such as classification, disease stage, diagnosis and Treatment monitoring.In this direction, Gibson and his colleagues propose
The concept of " blood information record ", the representative gene that the concept is selected by 10 from 9 axis.However, Shen
Ask someone to be intended to find to detect more convenient, spend lower, the less gene set of quantity is used as biomarker.
The content of the invention
Present invention aims at provide a kind of detecting system for detecting human immunity state.
A kind of detecting system for detection human immunity state that the present invention is provided, its detection includes the expression of following gene
Amount：IFI27、ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1、HP、ANXA3、
ARG1、FCGR1B、S100A12、MMP9、IL18R1、TLR5、GYG1、FCGR1A；On the expression quantity of foregoing any one or more gene
Adjust, then indicate that human immunity is not in good state.
The present invention provides a kind of diagnosis/detecting system, can detect the expression quantity of following any one or more gene：IFI27、
ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1、HP、ANXA3、ARG1、
FCGR1B, S100A12, MMP9, IL18R1, TLR5, GYG1, FCGR1A, and it is applied to evaluation human body immune state or disease
Sick diagnosis is assessed or medication evaluation more afterwards, and described disease is infection class disease, certainly immune class disease, cancer and cerebrovascular disease
Disease..
In above-mentioned diagnosis/detecting system that the present invention is provided, specifically, IFI27, ISG15, IFI44L, RSAD2,
The up-regulation of any one or more gene expression amount of HERC5, IFITM3, IFI44, IFIT3, EPSTI1, IFIT1, points out body to suffer from
Virus type catches；HP, ANXA3, ARG1, FCGR1B, S100A12, MMP9, IL18R1, TLR5, GYG1, FCGR1A are any
Or the up-regulation of multiple gene expression amounts, point out body to suffer from bacterium class infectious disease.
Further, described disease optimum decision system lupus erythematosus, prostate cancer, colorectal cancer, Kawasaki disease, childhood are special
Hair property arthritis, cerebrovascular disease, AIDS and/or pulmonary tuberculosis.
It will be appreciated by those skilled in the art that using real-time RCR, micro-array chip, RNA-Seq sequencings, customization
The technological means such as chip and targeting sequencing realizes the detection of the expression quantity of above-mentioned 20 genes and for human immunity state or disease
Disease is diagnosed or the instrument or system of assessment or medication evaluation belong to the protection domain of the application more afterwards.
The infection of detection virus type and the para-infectious detection examination of bacterium are being prepared the invention provides VRG genes and BRG genes
Application in agent box or the application in the detecting system for preparing detection human immunity state, the VRG genes include IFI27,
ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1；The BRG genes include HP,
ANXA3、ARG1、FCGR1B、S100A12、MMP9、IL18R1、TLR5、GYG1、FCGR1A。
Further, if the expression quantity of any one or more gene of VRG genes is significantly raised in body peripheral blood to be measured, carry
Show body to be measured suffer from virus type infectious disease, if in body peripheral blood to be measured any one or more gene of BRG genes table
Up to amount significantly up-regulation, body to be measured is pointed out to suffer from bacterium class infectious disease.
The invention provides application of the VRG genes in preparation system lupus erythematosus identification kit or preparing detection
Application in the detecting system of human immunity state, the VRG genes include IFI27, ISG15, IFI44L, RSAD2, HERC5,
IFITM3、IFI44、IFIT3、EPSTI1、IFIT1。
Further, if the expression quantity of any one or more gene of VRG genes is significantly raised in body peripheral blood to be measured, carry
Show that body to be measured suffers from SLE (systemic loupus erythematosus) and non-bacterial class infects.
The invention provides application of the HP genes in burn, wound, septicemia differential diagnosis kit or preparation is prepared
Or the application in the detecting system for preparing detection human immunity state.
Further, if HP gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out to suffer from
Burn, wound or septicemia.
The invention provides application of the HP genes in prostate cancer and colorectal cancer differential diagnosis kit is prepared.
Further, if HP gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out to suffer from
Advanced prostate cancer or colorectal cancer.
Exempt from the invention provides application of the ANXA3 genes in Kawasaki disease diagnostic kit is prepared or preparing detection human body
Application in the detecting system of epidemic disease state.
Further, if ANXA3 gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out to suffer from
Suffer from Kawasaki disease.
The invention provides ANXA3 genes in preparation system juvenile idiopathic arthritis and non-systemic Juvenile idiopathic
Application in arthritic differential diagnosis kit.
Further, if ANXA3 gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out to suffer from
Suffer from systemic juvenile idiopathic arthritis.
The invention provides application of the ANXA3 genes in juvenile idiopathic arthritis curative effect evaluation kit is prepared.
Further, if ANXA3 gene expression amounts are remarkably decreased in body peripheral blood to be measured, Juvenile idiopathic is pointed out
Arthritis curative effect is preferable.
The invention provides ARG1 genes prepare diagnosis and treatment of cerebrovascular diseases kit in application or prepare detect human body
Application in the detecting system of immune state.
Further, if ARG1 gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out to suffer from
Suffer from cerebrovascular disease.
There is the inspection of manifest symptom and non-manifest symptom preparing HIV-1 virus infection the invention provides ISG15 genes
Application in test agent box or the application in the detecting system for preparing detection human immunity state.
Further, if ISG15 gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out
HIV-1 virus the infecteds have manifest symptom.
The invention provides ISG15 genes are in the application prepared during AIDS curative effect assesses kit or preparing detection people
Application in the detecting system of body immune state.
Further, if ISG15 gene expression amounts are notable in body peripheral blood to be measured or decline, HIV-1 diseases are pointed out
Malicious the infected's curative effect is preferable.
The invention provides FCGR1A genes in identification active type pulmonary tuberculosis and resting form pulmonary tuberculosis kit is prepared
Using or prepare detection human immunity state detecting system in application.
Further, if FCGR1A gene expression amounts are significantly raised in body peripheral blood to be measured, body to be measured is pointed out
Suffer from active type pulmonary tuberculosis.
The invention provides application of the FCGR1A genes in pulmonary tuberculosis curative effect evaluation kit is prepared.
Further, if FCGR1A gene expression amounts are significantly lowered in body peripheral blood to be measured, active type lung is pointed out
Tubercular's curative effect is preferable.
The beneficial effects of the present invention are：The gene that the present invention is stated can instruct a variety of in the expression of peripheral blood
In terms of accurate parting, prognosis and the curative effect evaluation of disease.
Brief description of the drawings
3 width figures are entirety of 10 VRG genes in 3 groups of SLE (systemic loupus erythematosus) data in table 1 above Fig. 1
Change multiple, wherein, the width of upper left first is the data of PMBC, and the second width is peripheral blood whole blood data, the 3rd width
For RNAseq data；The distribution for the VRGs that two width are SLE below and Other diseases are contrasted.SoJIA is systemic juvenile in figure
Idiopathic arthritis, Staph is bacterial infection, and PSLE is Juvenile Systemic Lupuss Erythematosus.
Fig. 2 from left to right, it is left, in two width be ARG1 genes in stroke patient change multiple distribution；Right figure is ARG1
Distribution of the change multiple in ruptured intracranial aneurysms patient.
Two width are distribution situation of the ISG15 gene variations multiple in being in progress and getting nowhere type patient HIV above Fig. 3；Under
The width of face two is the distribution situation that ISG15 changes multiple after patient's HIV administration is handled.Chloroq is a kind of medicine name in figure；
Placebo is a kind of placebo.
Fig. 4 upper left and the width figure of upper right two are the change multiple of FCGR1A genes in active type and resting form pulmonary tuberculosis patient
In distribution；Lower-left figure be pulmonary tuberculosis patient treatment before and treatment 26 weeks after FCGR1A change multiple distribution；Bottom-right graph is lung
Tuberculosis patient disease neutralizes the distribution that FCGR1A after rehabilitation changes multiple.
Fig. 5 left figures are point of ANX3 gene variation multiples in systemic juvenile idiopathic arthritis and the contrast of other class diseases
Cloth；Right figure is the distribution that ANX3 changes multiple after juvenile idiopathic arthritis patient is administered.In figure, Canakinumab is medicine
Title；Placebo is a kind of placebo.
The upper figures of Fig. 6 are the survivorship curve of the prostate cancer patient of different HP gene variations multiples；Figure below the first from left is HP genes
Change distribution of the multiple in colorectal cancer different phase patient；Figure below middle graph is that prostate cancer patient's treatment feedback is different,
HP changes the distribution of multiple；Figure below right side one is the distribution of HP change multiples in different number tumour patients.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.Without departing substantially from spirit of the invention
In the case of essence, the modifications or substitutions made to the inventive method, step or condition belong to the scope of the present invention.
Unless otherwise specified, chemical reagent used in embodiment is skill used in conventional commercial reagent, embodiment
The conventional meanses that art means are well known to those skilled in the art.
The collection of the common data of embodiment 1
All data sets that the present invention is used are common data sets, and all from U.S.'s Biotechnology Information center
Gene expression data warehouse (the Gene of (National Center for Biotechnology Information, NCBI)
Expression Omnibus, GEO).Research is main to include two stages：Candidate gene and validation test candidate gene are selected,
Data set used is also classified into two batches：
1st, the data set that selection candidate gene is used
The selection of candidate gene is as Research foundation of the invention, and the selection of data set must have strict screening criteria：
(1) data must be by the filtering of pretreatment, i.e. the quality of data must reach a standard, and reduce error from data source header as far as possible；
(2) on the premise of the quality of data is ensured, the data as much as possible for obtaining infection or autoimmunity class disease；(3) data must
Must be whole blood data；(4) when for the follow-up differential gene expression screening of guarantee, the weight that every kind of disease data is contributed is tried one's best flat
Weighing apparatus, the disease of multi-group data is filtered out for correspondence disease type, and the present invention chooses one group of representative data.It is representative
There is the consideration of the following aspects：1. data sample amount is tried one's best greatly, to reduce data noise；2. detection time is tried one's best and connect now
Closely, becoming better and better with detection technique, it is believed that from now nearer data, it is also more accurate to detect；3. data sample is as far as possible
It is pure, i.e. sample or Healthy People, or only with studying corresponding disease, it is ensured that data it is pure also for reduction data
Noise.
More than after the screening of several steps, finally, first data set for being used to select candidate gene of the present invention is included altogether
18 groups of data, 20 kinds of disease types (wherein, data set GSE33341 and GSE72810 are respectively comprising two kinds of disease types), such as table 1.
It should be noted that data set GSE68310 and GSE45536 are the data of time series, the present invention is to have selected data sample
This first time point is used as experimental group number evidence.
For preceding 10 diseases in table 1, two major classes are classified as：1. bacterium infection class disease and 2. virus infection class disease
Disease, 5 groups of data are included per class.In candidate gene screening, performance of the gene detuning frequency in each class is also choosing of the present invention
The important references taken.
2nd, the data set that validation test candidate gene is used
Choose after candidate gene, it is necessary to be verified in multigroup independent data.Data set for checking is equally needed
Will be by the filtering of pretreatment.The present embodiment mainly introduces the data set that 6 aspect checkings are used：
(1) it is used to distinguish bacterium infection and the used data set of virus infection：GSE72829、GSE60244、GSE6269
And GSE42026.Every group of data decimation bacterium infection and the sample of virus infection are used to cluster；
(2) shared in being verified to systemic loupus erythematosus (Systemic Lupus Erythematosus, SLE) disease
6 groups of data, be respectively：GSE11907, GSE49454, GSE72509, GSE17755, GSE29536 and GSE22098.Wherein
GSE11907 is the number of PMBC (Peripheral Blood Mononuclear Cell, PBMC) gene expression
According to other is the data of whole blood gene expression；And GSE72509 is the data being sequenced in the generations of RNAseq bis-, other is chip-count
According to；
(3) individual gene be modeled in independent data verify, this module altogether using 4 class diseases (burn, septicaemia, wound,
Kawasaki disease), 8 groups of data：GSE37069 and GSE19743, GSE69528 and GSE80496, GSE36809 and GSE11375,
GSE63881 and GSE68004；
(4) single-gene mark is in AIDS virus (Human Immunodeficiency Virus, HIV) infection data
Checking；Altogether comprising 4 groups of data：GSE6740, GSE56837, GSE71063 and GSE44228.Wherein, preceding two groups of data are Chinese mugworts
Grow virus has the data got nowhere in the sample, and rear two groups of data are the data to AIDS patients drug therapy；
(5) checking gene FCGR1A mark is acted in pulmonary tuberculosis (tuberculosis, TB)；4 groups of data are collected altogether：
GSE37250, GSE40553, GSE31348 and GSE56153.Wherein preceding two groups are active tuberculosis (Active TB) and latent
Volt property pulmonary tuberculosis (Latent TB) data, latter two groups are pulmonary tuberculosis patient treatment or the data cured；
(6) for systemic juvenile idiopathic arthritis (Systemic Juvenile Idiopathic Arthritis,
SJIA), the present invention have collected two groups of data：GSE13501 and GSE80060.
Previous group is used for the contrast of systemic juvenile idiopathic arthritis and Other diseases, and later group is controlling for such disease
Treat data.
Some are used for the data used in other checkings, due to not being the emphasis of this research, just do not enumerate here
.The data for being enumerated above out have nearly 50 groups, and data are filtered after some are not individually listed and some pretreatments, this
Embodiment does not show that the data handled in research have nearly hundred groups one by one, is that data volume is very big, and covering is comprehensive.
Expressed for 20 genes of involved disease in this table 1 and 4 in periphery stabilizing blood crt gene (ACTB,
B2M, UBC and GUSB), the present invention sets up healthy control group and relevant disease group, determines kit needed for collection of specimens and experiment
Scale.Disease peripheric venous blood involved by normal healthy controls crowd and this patent is gathered using PAXgene heparin tubes, and is turned
- 80 DEG C of cryopreservation tube is moved to freeze.
By 5000rpm centrifugations 10min at 4 DEG C of PAXgene Blood RNA pipes, abandon after supernatant plus 350 μ L Buffer BR1
Dissolving precipitation, the sample after dissolving is transferred in 1.5mL eppendorf pipes, then adds 300 μ L Buffer BR2 and 40 μ L eggs
White enzyme K, whirlpool concussion is mixed 5 seconds, is then incubated 10min in 55 DEG C of 1000rpm shaking tables.Liquid is transferred to after cracking and is cased with
In PAXgene Shredder spin column 2mL centrifuge tubes, supernatant is carefully transferred to newly by 15000rpm centrifugation 3min
1.5mL eppendorf pipes in.Detailed step is with reference to PAXgene Blood RNA kit kit specifications.With ultraviolet point
260/280 ratio and RNA concentration of light photometer Detection and Extraction total serum IgE.
Can be according to nCounter XT CodeSet Gene when extracting the ratio of total serum IgE 260/280 between 1.7-2.3
The operation of Expression Assays specifications requires to be detected.Added first in the pipe comprising Reporter CodeSet
70 μ L Hybridization buffer, upset mixes and initial mixing reaction solution is made.Then in each hybridization reaction pipe
It is separately added into the sample total serum IgE that 8 μ L initial mixings reaction solutions and 1.5-5 μ L are extracted.2 μ L captures are added into each reaction tube again
ProbeSet simultaneously overturns mixing, and 15 μ L hybridization reaction systems are made, is immediately placed in the thermal cycle heater for being preheated to 65 DEG C, incubates
Educate at least 16h.Detailed step referenceXT Assay specifications.
With nCounter analysis systems and software kit NanoString ' s free nSolverTMAnalysis software is miscellaneous
The fluorescence probe intensity image of reaction solution after friendship, to ensure the reliability of data, sample concentration dilution is analyzed for one times.
The processing method of the data of embodiment 2
1st, chip data handling process all in the present invention
Because data volume is very big, the present invention does not use original chip data, but uses and provided in each research
Expression value matrix data.These expression value matrixs are all that each seminar is pretreated, however, due to chip platform not
Together, the laboratory of research is different, and experimental enviroment is different, and the mode of each laboratory pretreatment is different, and the data taken are simultaneously
It can not directly use, and to pass through strict screening and filtering.For the pretreatment again and filtering of these data, there is several tight
The filter criteria of lattice, it is specific as follows：
(1) all expression values need logarithm (log) to handle；
(2) unqualified value (including missing, the or unreasonable) ratio of each probe in all samples must not be higher than setting
Fixed threshold value (50% is used in this research), otherwise filters out this probe；
(3) ratio of each underproof probe of sample (including missing values, or unreasonable value) must not be higher than the threshold set
It is worth (50%), otherwise filters out this sample；
(4) lower bound is carried out to all expression values to block.
Under normal circumstances, or the data of a research are that whole expression values took logarithm, otherwise it is whole expression
Value did not take logarithm, the data for not taking logarithm, only needs whole logarithm process, then proceedes to filtering below.
Certainly, there are some data, formally see, it should be that part has taken logarithm, part is not taken the logarithm.For such number
According to due to having retained for the quality of data, way of the invention is to give up.Every such data, without exception without.
(2) the unreasonable value in (3) step refers to, because the collection of chip data is obtained by measuring fluorescent value, and table
If too small up to being worth, covered by background, so that the expression value of measurement is by serious distortion.Thus in processing procedure, expression
Value is less to be referred to as in unreasonable value, the present invention, and the standard of selection is【log2(100)】。
(4) step blocks finger, after the filtering of (2) (3) step, has only filtered probe and sample, for some probes, its
In whole samples, unreasonable worth ratio is less than 50%, thus this probe is not filtered, and for such situation, is made
With a reference value log above2(100)。
Adhere to never using data with the difference in processing procedure, the present invention in order to avoid different experiments room is measured, even if
Two groups of data sample targets are consistent, are the data for same disease.It should be strongly noted that there are some data to be with
Standardized centered on 0, such data all crossed by logarithm process, need not generally also do the truncated position of (4) step
Reason.
2nd, differential expression
Differential expression analysis is carried out to data from the RP methods in RankProd bags in R language.RP is a kind of nonparametric
The method of statistics, for the data for repeating experiment, variable (gene, probe, the metabolic molecule unanimously lacked of proper care can be detected
Deng), it is widely used in biological group and learns data.This method has some hypothesis for data：
(1) in the feature of all measurements, the feature of imbalance only accounts for the sub-fraction of sum；
(2) in multiple repetition experiment, detection is independent；
(3) all variations are independent；
(4) the detection variance of all detections is stable.
On the basis of the above hypothesis, this method can calculate each variable it is used repeat to test in make a variation multiple
The ranking (rank) of (Fold Change, FC), to these ranking computational geometry averages, obtains RP values, and RP values are smaller, and more have can
It can be imbalance variable.
For the reduction data noise of maximum possible, further sieve has been done for the difference expression gene that RP is calculated
Choosing, mainly there is two indices：
P values：The P values of all differences expressing gene are necessarily less than 0.05；
Make a variation multiple：Variation multiple selection have two stages, for difference expression gene preliminary filtering when, from threshold
It is worth for 1.5 or 0.7；In the selection of further candidate gene, for repressor gene number, reduce noise, use instead threshold value 2 or
0.5。
3rd, the machine learning model used
The present invention is used to two bare metal learning models altogether：Logistic regression (logistic regression) mould
Type and K averages (K-means) Clustering Model.
Logic Regression Models are a kind of generalized linear regression model (generalized linear model), but are different from
General regression model, Logic Regression Models are mainly used in data classification problem, and classical Logic Regression Models are used for two classification
Problem.
Logarithm probability function is a kind of Sigmoid functions, and the value of the z in formula is converted into one close to 0 or 1 y by it
Value, and the value of its output changes very precipitous near z=0.Logic Regression Models have many advantages：Model directly can to classification
Energy property is modeled, it is not necessary to which data are distributed with prior hypothesis；Model can not only predict the classification of data, Er Qieke
To obtain the prediction probability of correspondence classification, for needing the task using probability aid decision, this information is particularly important；This
Outside, the model can arbitrary order can lead, which determining it has very outstanding mathematical property, in that context it may be convenient to ask for optimal solution.
Logistic regression is a kind of method of supervised learning.For several disease classes verified with independent data sets in table 3
Type, is verified using the model to corresponding data modeling, have received good effect.
From literal above it can also be seen that K mean cluster is a kind of Clustering Model.Cluster is a kind of unsupervised study, on
The logistic regression classification stated is a kind of model of supervised learning.Cluster and the maximum difference of classification are that the target of classification is prior
, it is known that and clustering then different.The object that Clustering Model almost can apply in all objects, cluster is more similar, the effect of cluster
Fruit is better.Why it is referred to as K mean cluster and is because it is it can be found that different k clusters, and the center of each cluster is used in cluster
Contained worth mean value computation.Specific workflow is as follows：First, it is random to determine that k initial point is barycenter；Then, it is right
Not individual point is to k centroid calculation distance, wherein minimum from a distance from that barycenter, the point is just assigned to the class where the barycenter；
Then, wait and distribute a little, average is calculated to every cluster, from the barycenter for being newly appointed as the cluster；Above step is repeated, until
The data stabilization included per cluster.
Used in the present invention is two points of K mean algorithms, and some candidate factors found using inventor do vector,
With K mean algorithms, the sample of the whether viral infection class disease of observation and the sample of bacterium infection class disease truly have difference, can
It is gathered in different classifications.
The selection of the candidate gene of embodiment 3
The difference expression gene tentatively obtained for the 20 groups of data disclosed based on table 1 in embodiment 1 is, it is necessary to further
Screening, obtains the candidate gene of research.
First, FC filtering is carried out to each group of difference expression gene, selects FC>2 or FC<0.5 imbalance gene.
It can be seen that the threshold value used almost harshness, because wishing that the candidate gene found has very strong anti-interference.Then,
The difference expression gene of 20 groups of data is counted and merged, and by counting size inverted order ranking.Finally, the ranking based on more than, knot
The observation to the uniformity of gene expression in two class data sets (bacteria-related diseases data and virus associated-diseases data) is closed, most
10 BRGs gene and 10 VRGs gene are selected eventually.Such as table 2.
Table 2 distinguishes bacterium infection and virus infection using BRGs and VRGs
| Data set | The factor | TP | FN | FP | TN | F1 |
| GSE72829 | NG_V；NG_B | 27 | 1 | 5 | 18 | 0.90 |
| GSE60244 | NG_V；NG_B | 55 | 1 | 16 | 21 | 0.87 |
| GSE6269 | NG_V；NG_B | 61 | 3 | 12 | 15 | 0.89 |
| GSE42026 | NG_V；NG_B | 33 | 7 | 8 | 11 | 0.81 |
Note：Clustered using K-means；TP：True positives；FN：False negative；FP：False positive；TN：True negative；F1：F1 standards；
NG_V：Change the number that multiple is more than 2 in VRGs；NG_B：Change the number that multiple is more than 2 in BRGs.
Collect on infecting the common data with the blood transcript profile of autoimmunity class.According to the quality of data, each disease
Disease, which selects one group of representational data, (must be the data of whole blood, be shown in Table 1).Differential expression point is carried out to this 20 groups of data first
Analyse (patient is to Healthy People).In order to reduce the number of significant difference gene, very strict screening conditions --- the multiple of selection
Change (Fold Change, FC) have to be larger than 2 (up-regulated genes), or less than 0.5 (down-regulated gene).Then, it is these are notable
The superincumbent 20 groups of data of gene in occur frequency sequence.Lost it was observed that showing significant function in these disease classes
Adjust, and these high genes of the frequency of occurrences, it is essentially all the gene of up-regulation.In further genescreen, the present invention
Target be that number gene is reduced to 20, so as to obtain the detection of convenient material benefit.Due in bacterial infective diseases class
In virus infection class, the imbalance of gene shows very strong uniformity, so the present invention have chosen virus infection class disease
Sick 10 related up-regulated genes 10 up-regulated genes related to bacterium infection class disease.
These up-regulated genes related to virus infection class disease are how relevant with interferon signal, include among these
IFI27, IFI44L, RSAD2, HERC5, IFITM3, IFI44, IFIT3, EPSTI1, IFIT1 and ISG15.And and bacterium infection
The related up-regulated gene of class disease is how related to various paths, among these including HP, ANXA3, FCGR1B, S100A12, MMP9,
IL18R1, TLR5, GYG1, FCGR1A and ARG1.This 10 " virus gene (Virus-response Genes, VRGs) " exist
Average fold change reachable 4.61 to 29.13 in virus infection class disease.For 10 " bacterium genoid (Bacteria-
Response Genes, BRGs) " change of multiple in bacterium infection class disease also reaches 4.44 to 14.28.The present invention is also
It was observed that, either " virus gene " still " bacterium genoid " all only has higher table in disease class corresponding to itself
Reach, and change multiple in the disease class of other side and be respectively less than 2.The present invention have collected four kinds while comprising virus infection and bacterium sense
The data set of dye, from table 2 it can be seen that using these genes, very accurate to two class classifications of diseases, F1 values can reach
0.81 to 0.91.
To except virus infection or bacterium infection 10 groups of data in addition to the corresponding disease of 10 groups of data checking in, this
Invention finds that either " virus gene " or " bacterium genoid " is up-regulated gene mostly in these disease classes, such as table 3.
It is different with other diseases class in the sample of burn and general sexual trauma (injury), present invention discover that " bacterium genoid " table
Reveal obvious up-regulation, and " virus gene " has and several shows downward.In chorionitis (scleroderma) and primary
Property dry syndrome (primarySyndrome) in sample, " virus gene " shows obvious up-regulation；In meat
In the sick and common variation immune deficiency disorder sample of shape knurl, " virus gene " shows appropriate up-regulation, and simultaneous is " thin
FCGR1A and FCGR1B up-regulation in mushroom gene "；In the sample of Kawasaki disease and the juvenile idiopathic arthritis of systematicness, except
FCGR1A and FCGR1B, other " bacterium genoids " shows significant up-regulation；In addition, in rheumatic arthritis sample
In, " bacterium genoid " is also observed appropriate up-regulation；Pulmonary tuberculosis is only one " virus gene " and " bacterium class base
Cause " shows as a kind of disease of up-regulation, however, the FCGR1A and FCGR1B in " bacterium genoid " but show it is abnormal prominent
The up-regulation gone out.Generally, 20 include " virus gene " and " bacterium genoid " performance in infection and autoimmune disease
Go out and frequently lack of proper care, and the different mode that these are observed is worth the extra research of increase to its deep understanding.
In uremia (uremia), psoriasis (psoriasis), ankylosing spondylitis (ankylosing
) and chronic obstructive pulmonary disease (chronic obstructive pulmonary disease, COPD) spondylitis
In data set, the imbalance of these genes is not observed.
Gene imbalance in SLE diseases
Systemic loupus erythematosus is the disease that only a few has quality data, therefore, and this disease turns into one
The relatively good candidate disease that can be used for test.In the data of systemic loupus erythematosus whole blood, the present invention observes foregoing
" virus gene " VRG has the up-regulation of highly significant, and the variation multiple of some genes is up to as many as 10 times, such as Fig. 1.In peripheral blood
Up-regulation Fig. 1 of such great exaggeration is equally occurred in that in unicellular data, also, in RNA-seq microchip data, this
The up-regulation pattern of sample is still present.Due to " virus gene " in systemic loupus erythematosus disease the multi-level height of up-regulated expression
Spend uniformity, it is easy to use " virus gene " sample with such a disease bacterium infection and itself is exempted from from including
Distinguished in the disease of epidemic disease, such as Fig. 1.It is observed that in patient's sample more than 90%, the coefficient of variation is up to more than 2 times
" virus gene " number does not have such phenomenon at least more than 5 in other class diseases.
Single-gene is used as the biomarker under the conditions of under disease
From the case of systemic loupus erythematosus, the common tune of " virus gene " and " bacterium genoid " imbalance observed
Section pattern, by multiple trial, the present invention finds 4 kinds while have the data of training set and test set, only by 1 gene
Variation multiple just can reach very outstanding parting effect.Wherein, septicaemia, burn and general injury are only existed by gene HP
Distinguish patient and Healthy People sample in test set F1 up to 0.99-1.For Kawasaki disease, only by Gene A NXA3 expression variance
The F1 of the differentiation of patient and Healthy People can be just set to reach 0.97.Such as table 3.
Table 3 infects and the single-gene biomarker in autoimmunity class disease in several classes
| Disease | Training set | Test set | Gene | TP | FN | FP | TN | F1 |
| Burn | GSE37069 | GSE19743 | HP | 112 | 2 | 1 | 62 | 0.99 |
| Septicaemia | GSE69528 | GSE80496 | HP | 24 | 0 | 0 | 21 | 1.00 |
| Wound | GSE36809 | GSE11375 | HP | 155 | 3 | 0 | 26 | 0.99 |
| Kawasaki disease | GSE63881 | GSE68004 | ANXA3 | 75 | 1 | 4 | 33 | 0.97 |
Note：Logic Regression Models are used
The disease that biomarker is not limited to infection and autoimmunity is made of single-gene.Present invention discover that in cerebrovascular class
Some diseases in, including apoplexy, ruptured intracranial aneurysms etc., it is foregoing that " bacterium genoid BRG " has consistent imbalance.At this
A bit in " bacterium genoid ", ARG1 expression has a reliable differentiation to patient and Healthy People.Such as Fig. 2.In this several groups of data
In, the expression variance multiple for having the ARG1 of 72-74% patient exceed 2.And have the ARG1 of 87-100% Healthy Peoples expression
Multiple make a variation less than 2.Thus, perhaps ARG1 can play indicative function to the recovery of cranial vascular disease.
The single-gene biomarker of HIV diseases
HIV can cause the obvious up-regulation (such as Fig. 3) of " virus gene ".Because IFI27 is in many diseases, especially
In the related disease of virus infection, there is significant up-regulated expression, thus, when the disease mixed in data is more, IFI27 is just
It is not suitable as biomarker.Present invention discover that ISG15 can be a reliable mark.Using ISG15 expression,
There is extraordinary differentiation to the HIV patient of Advancement Type and the type that gets nowhere.In two groups of checking data of GSE6740 and GSE56837
In, the ISG15 expression variance multiples of 91-95% Advancement Type HIV patient have more than 2 in the type HIV sample that gets nowhere
87-100% patient ISG15 variation multiple is less than 2.In addition, in the data of drug treatment, ISG15 expression also has bright
Aobvious indicative function.From two groups of data of GSE71063 and GSE44228, it can be seen that after the patient for having 50-67% is administered,
ISG15 expression is lowered up to as many as 2 times, and is only taken in placebo sample, and the ISG15 expression without any sample is lowered
Reach 2.
The single-gene biomarker of pulmonary tuberculosis disease
Pulmonary tuberculosis is a kind of very special disease, and it is existing that " virus type " and " bacterium class " two genoids show imbalance
As.However, all " virus gene " VRG up-regulated expressions in patient's sample do not have uniformity, so as to find suitable list
Gene biological mark.And in " bacterium genoid " BRG, present invention discover that FCGR1A can be used as a reliable biological mark
Will thing (Fig. 4).Using FCGR1A expression, active tuberculosis and latent tuberculosis can be accurately distinguished.
In GSE37250 data, the FCGR1A of 87% active tuberculosis patient expression variance multiple is higher than 5, and in GSE40553
In data, the FCGR1A of all active tuberculosis patient expression is higher than 4, and in two groups of data, latent tuberculosis disease
The FCGR1A of people expression is under corresponding threshold value, only 2-3%.In the data of drug treatment, FCGR1A expression is still
There is significant effect.It can see, after treatment after a while, have from two groups of data of GSE31348 and GSE56153
The FCGR1A expression of 85-96% patient has notable downward.
The single-gene biomarker of systemic juvenile idiopathic arthritis disease
Systemic juvenile idiopathic arthritis is usually associated with the up-regulation of " bacterium genoid ".The present invention is collected
To several groups of data in find ANXA3 can as such disease biomarker.Such as Fig. 5.In systematicness and non-systemic
Juvenile idiopathic arthritis sample in, it is only different as distinguishing with ANXA3 expression, with regard to very high accuracy rate can be obtained.
In this group of data of GSE13501, the ANXA3 of 81% systemic juvenile idiopathic arthritis expression variance multiple is big
In 3, and nonsystematic juvenile idiopathic arthritis patient has in the sample higher than 91%, and ANXA3 expression variance multiple is less than
3。
ANXA3 expression can be used for detecting the situation of such patient's drug treatment.
GSE80060 is the data of one group of systemic juvenile idiopathic arthritis patient administration processing, by observing gene
ANXA3 expression, the expression for having 42% patient ANXA3 upon administration is lowered more than 2.5 times, and takes placebo patient
Do not find that ANXA3 expression is lowered yet.
The single-gene biomarker of cancer
Immune response system related genes equally show as up-regulation in the peripheral blood of cancer patient.It is collected into the present invention
In the related data of cancer, gene HP shows the property of good biomarker.Such as Fig. 6.In this group of colorectal cancer
In data, from the figure, it can be seen that in the patient in the CD stages, the variation multiple of 50% patient's HP genes is more than 5, and AB
The patient in stage does not but make a variation multiple more than 5.In another group of primary tumor data, the sample of only double primary tumors
The HP genetic mutations multiple that 30% sample is there are about in this is more than 2.The expression of gene HP can be used for clinical diagnosis.At two groups
In the data of prostate cancer, HP higher expression has corresponded to poorer diagnosis.From the survival curve in figure, one is clearly seen that
Individual phenomenon：HP higher expression, the time of the survival of its sample finally is shorter on the contrary.To sum up in several data sets gene HP table
Existing, gene HP is that can do the mark of biology in this few class cancer.
In the research of many cells types of tissue, when cellular component changes, the complexity and difficulty of research are also significantly
Increase.Therefore, if above-mentioned described detuning phenomena has cellular component to change, it is possible to found out difference can be caused
Expressing gene has deviation.However, the present invention is in several groups of data comprising different cellular components, it was found that identical imbalance mould
Formula.For example, GSE11907 is the PBMC data of one group of systemic Erythematosus Disease, and in the analysis of this group of data, same hair
Show the detuning phenomena of " virus gene ", see Fig. 1.In the analysis of HIV data, either data of whole blood, and or
It is CD4+ and CD8+ data, it can be found that in Advancement Type HIV samples and getting nowhere type HIV samples in " virus gene "
Difference.Research although a distinction between cellular component can obtain more detailed information, however, from the above analysis, can see
Arrive, only may be enough using only the analysis of the data of whole blood for many diseases.
House-keeping gene in blood
House-keeping gene would generally be used as a kind of self-checking standard tested, such as RT-PCR.Present invention discover that there is some bases
Because there is highly stable expression in the data of these diseases, including some all familiar genes：ACTB、B2M、
UBC and GUSB.Therefore, whether inventor's guess can use the expression ratio of 20 genes and house-keeping gene, replace above-mentioned work
In variation multiple be used for classify, diagnose and treat assessment.As one kind checking, inventor uses B2M as control, in lung knot
Some checkings have been done in core and cancer.The result of ultimate analysis with it is above-mentioned with the analysis result of healthy persons being used as control be very consistent
's.This result is very meaningful, because selection as a control group is more complicated, or the possibility chosen is improper,
These all can be influential on follow-up analysis result, and selecting house-keeping gene as to note makes analysis result more
It is stable.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (10)
1. a kind of detecting system for detecting human immunity state, it is characterised in that detecting system detection includes following gene
Expression quantity：IFI27、ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1、HP、
ANXA3、ARG1、FCGR1B、S100A12、MMP9、IL18R1、TLR5、GYG1、FCGR1A；The table of foregoing any one or more gene
Up to amount up-regulation, then indicate that human immunity is not in good state.
2. a kind of diagnosis/detecting system, it is characterised in that the expression quantity of following any one or more gene can be detected：IFI27、
ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1、HP、ANXA3、ARG1、
FCGR1B, S100A12, MMP9, IL18R1, TLR5, GYG1, FCGR1A, and it is applied to evaluation human body immune state or disease
Sick diagnosis is assessed or medication evaluation more afterwards, and described disease is infection class disease, certainly immune class disease, cancer and cerebrovascular disease
Disease.
3.VRG genes and BRG genes are preparing the infection of detection virus type and the para-infectious detection kit of bacterium or detection human body
Application in the detecting system of immune state, the VRG genes include IFI27, ISG15, IFI44L, RSAD2, HERC5,
IFITM3、IFI44、IFIT3、EPSTI1、IFIT1；The BRG genes include HP, ANXA3, ARG1, FCGR1B, S100A12,
MMP9、IL18R1、TLR5、GYG1、FCGR1A。
Application of the 4.VRG genes in preparation system lupus erythematosus identification kit, the VRG genes include IFI27,
ISG15、IFI44L、RSAD2、HERC5、IFITM3、IFI44、IFIT3、EPSTI1、IFIT1。
5.HP genes are preparing burn, wound, septicemia differential diagnosis kit or prostate cancer and colorectal cancer antidiastole
Application in the detecting system of kit or detection human immunity state.
Application of the 6.ANXA3 genes in preparing Kawasaki disease diagnostic kit or detecting the detecting system of human immunity state.
7.ANXA3 genes are examined in the discriminating of preparation system juvenile idiopathic arthritis and non-systemic juvenile idiopathic arthritis
Application in disconnected kit or juvenile idiopathic arthritis curative effect evaluation kit.
Application of the 8.ARG1 genes in preparing diagnosis and treatment of cerebrovascular diseases kit or detecting the detecting system of human immunity state.
There is the detection kit or AIDS of manifest symptom and non-manifest symptom preparing HIV-1 virus infection in 9.ISG15 genes
Application in the detecting system of sick curative effect evaluation kit or detection human immunity state.
10.FCGR1A genes prepare identification active type pulmonary tuberculosis and resting form pulmonary tuberculosis kit in application or preparing lung
Application in tuberculosis curative effect evaluation kit.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107475258A (en) * | 2017-08-22 | 2017-12-15 | 中山大学肿瘤防治中心 | A kind of RNAcircEPSTI1 and its application in three cloudy breast cancer |
| CN107523626A (en) * | 2017-09-21 | 2017-12-29 | 顾万君 | One group of peripheral blood gene marker for being used for active tuberculosis non-invasive diagnosis |
| CN108034716A (en) * | 2018-01-24 | 2018-05-15 | 广州奥百阕谱生物科技有限公司 | For differentiating whether patient infects and infect the kit of species |
| CN108959843A (en) * | 2018-06-06 | 2018-12-07 | 北京大学 | The chemical small molecule drug computational screening method of targeted rna |
| CN111489829A (en) * | 2020-05-29 | 2020-08-04 | 杭州广科安德生物科技有限公司 | Method for constructing mathematical model for detecting pancreatic cancer in vitro and application thereof |
| WO2023281225A3 (en) * | 2021-07-08 | 2023-03-23 | bioMérieux | Method and kit for detecting a replicating respiratory virus |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102128935A (en) * | 2010-11-23 | 2011-07-20 | 中生北控生物科技股份有限公司 | Method for detecting hoptoglobin in serum and detecting kit thereof |
| CN102402650A (en) * | 2001-11-09 | 2012-04-04 | 生命技术公司 | Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles |
| CN103119444A (en) * | 2010-04-21 | 2013-05-22 | 米密德诊断学有限公司 | Signatures and determinants for distinguishing between a bacterial and viral infection and methods of use thereof |
| CN103732251A (en) * | 2011-05-25 | 2014-04-16 | 米迪缪尼有限公司 | Methods of treating systemic lupus erythematosus, scleroderma, and myositis with an antibody against interferon-alpha |
-
2017
- 2017-03-17 CN CN201710162227.XA patent/CN107058521B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102402650A (en) * | 2001-11-09 | 2012-04-04 | 生命技术公司 | Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles |
| CN103119444A (en) * | 2010-04-21 | 2013-05-22 | 米密德诊断学有限公司 | Signatures and determinants for distinguishing between a bacterial and viral infection and methods of use thereof |
| CN102128935A (en) * | 2010-11-23 | 2011-07-20 | 中生北控生物科技股份有限公司 | Method for detecting hoptoglobin in serum and detecting kit thereof |
| CN103732251A (en) * | 2011-05-25 | 2014-04-16 | 米迪缪尼有限公司 | Methods of treating systemic lupus erythematosus, scleroderma, and myositis with an antibody against interferon-alpha |
Non-Patent Citations (8)
| Title |
|---|
| EDOARDO MALFATTI等: "A New Muscle Glycogen Storage Disease Associated with Glycogenin-1 Deficiency", 《ANN NEUROL》 * |
| ICHCHHA MADAN等: "The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancy", 《JOURNAL OF PERINATAL MEDICINE》 * |
| JARI NUUTILA等: "Distinction between bacterial and viral infections", 《CURRENT OPINION IN INFECTIOUS DISEASES》 * |
| 李伟等: "不同乳腺癌细胞系中 TLR5 和 NLRC4 受体的表达和定位", 《中国免疫学杂志》 * |
| 李萍等: "结合珠蛋白在几种皮肤病中表达的研究", 《中华医学杂志》 * |
| 杜林栋等: "前列腺癌诊断标志物研究现状", 《临床泌尿外科杂志》 * |
| 贺骞等: "钙结合蛋白S100A12在动脉粥样硬化中的作用", 《国际心血管病杂志》 * |
| 黄娟妮等: "炎症微环境下代谢基因ARGl对结直肠癌细胞增殖的影响研究", 《消化肿瘤杂志》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107475258A (en) * | 2017-08-22 | 2017-12-15 | 中山大学肿瘤防治中心 | A kind of RNAcircEPSTI1 and its application in three cloudy breast cancer |
| CN107523626A (en) * | 2017-09-21 | 2017-12-29 | 顾万君 | One group of peripheral blood gene marker for being used for active tuberculosis non-invasive diagnosis |
| CN107523626B (en) * | 2017-09-21 | 2021-04-13 | 顾万君 | Group of peripheral blood gene markers for noninvasive diagnosis of active tuberculosis |
| CN108034716A (en) * | 2018-01-24 | 2018-05-15 | 广州奥百阕谱生物科技有限公司 | For differentiating whether patient infects and infect the kit of species |
| CN108034716B (en) * | 2018-01-24 | 2021-06-25 | 广东辉锦创兴生物医学科技有限公司 | Kit for identifying infection and infection type of patient |
| CN108959843A (en) * | 2018-06-06 | 2018-12-07 | 北京大学 | The chemical small molecule drug computational screening method of targeted rna |
| CN108959843B (en) * | 2018-06-06 | 2021-07-06 | 北京箭牧科技有限公司 | Computer screening method of chemical small molecule drug of target RNA |
| CN111489829A (en) * | 2020-05-29 | 2020-08-04 | 杭州广科安德生物科技有限公司 | Method for constructing mathematical model for detecting pancreatic cancer in vitro and application thereof |
| WO2023281225A3 (en) * | 2021-07-08 | 2023-03-23 | bioMérieux | Method and kit for detecting a replicating respiratory virus |
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