CN109979598A - Use human body18F-FDG PET data analyzes tissue DNA methylol background and application - Google Patents
Use human body18F-FDG PET data analyzes tissue DNA methylol background and application Download PDFInfo
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Abstract
The invention discloses with human body18F-FDG PET data analyzes tissue DNA methylol background and application, including obtains adult18F-FDG whole body faultage image；It extracts the 18F-FDG data of each target tissue and calculates glucose uptake rate, and set up and corresponded to by Sex, Age18The database of F-FDG uptake ratio；It according to each target organ tissue database background of normal adult and its fitting, corrects DNA telomere and linearly shortens curve, establish the operational module of analysis measurement DNA methylol background；Measure tissue specificity DNA methylol background Primary parameter and tissue specificity DNA methylol background secondary parameters.The present invention provides a kind of methods that non-invasive analyzes measurement body tissue's specific DNA methylol background, can provide effective gene molecule Informational support for the personalized prevention and treatment of slow disease and rehabilitation and personalized health care health and precisely medical treatment research and development.
Description
Technical field
The present invention relates to medicine bioengineering and big health field more particularly to a kind of use human body18F-FDG PET data analysis group
Knit DNA methylol background and application.
Background technique
Great chronic disease has become the chief threat of human health, mainly include cardiovascular and cerebrovascular disease, cancer,
The diseases such as chronic respiratory disease, diabetes and mouth disease and endocrine, kidney, bone, nerve.
The reason of leading to great chronic disease 80%, blames on others internal and external poor environment, including cell ageing,
Harmful substance, inflammatory factor, bad life habits, unscientific nutrition, shortage movement and environmental pressure etc..And apparent gene
(group) is exactly the bridge between environment and chronic disease.It is detached from the tissue-specific gene methylation background of the right path, is apparent base
Because of abnormal feature sex expression, the several years even many decades before disease generation, gene methylation background just has already appeared different
Often.Gene methylation Anomalies of Backgrounds, leads to various abnormal gene expressions, not only will affect health and service life, leads to cardiovascular and cerebrovascular
Disease, diabetes and nervous system disease can also cause fixed mrna instability, gene mutation and tumor suppressor gene silent, be to induce
Cancer and the major reason for promoting tumor recurrence transfer.Since everyone cell ageing position, range and degree are different,
Poor environment situation inside and outside body is different, just creates our everyone different tissue-specific genes and methylates
Background.Everyone apparent gene individualized feature is only grasped, health could be carried out with disease effective personalized dry
In advance, it so that the morbidity and mortality of great chronic disease be effectively reduced, and is finally reached and improves health conditions and promote longevity
General objective.
Currently, the method for having developed various detection DNA methylation backgrounds both at home and abroad, wherein passing through blood cell, saliva
High altitude may be implemented in liquid cell.However, since histiocytic otherness each in body is big, in addition environmental activity
Again different in the target organ effect of human body, the detection means of these single cells or single organization can not accomplish hurtless measure
Property the entire human body of description DNA methylation background.In recent years, a large amount of studies have shown that the glucose uptake of body cell with
DNA methylol background, the tight association on many signal paths.Therefore it is surveyed using the analysis of 18F-FDG PET molecular image data
Tissue specificity DNA is determined, to evade the deficiency of existing detection DNA methylation background method whereby.
Summary of the invention
Goal of the invention: in order to overcome the deficiencies in the prior art, the present invention provides a kind of with 18F-FDG PET points
Sub-image data analysis measurement tissue specificity DNA methylol background method and application, to realize the effective of human body gene information
It feasibly develops and uses, overcomes deficiency present in above-mentioned existing DNA methylation context analyzer determination techniques, while being individual character
Change slow disease prevention and treatment and rehabilitation, personalized health care health, promote health with it is long-lived provide human body gene molecular data, technical support,
Personalized health consulting and guidance.
Technical solution: to achieve the above object, a kind of use of the invention18The analysis measurement of F-FDG PET molecular image data
Tissue specificity DNA methylol background method, this method extract tissue specimen without biopsy, by extracting any target organ group
The 18F-FDG PET image data knitted, calculates each target organ tissue glucose uptake ratio, the analysis mould established by the present invention
Block can grasp everyone each organ-tissue gene methylation background information more fully hereinafter.The following steps are included:
(1) adult is obtained18F-FDG whole body faultage image；
(2) ROI method or SUV value method are used, the 18F-FDG data of each target tissue are extracted and calculates glucose uptake rate,
And it sets up and is corresponded to by Sex, Age18The database of F-FDG uptake ratio；
(3) it according to each target organ tissue database background of normal adult and its fitting, corrects DNA telomere and linearly shortens song
Line establishes the operational module of analysis measurement DNA methylol background；
(4) tissue specificity DNA methylol background Primary parameter and tissue specificity DNA methylol background two are measured
Grade parameter.
Further, human body is obtained using Positron emission computed tomography instrument18The non-correction for attenuation of F-FDG PET is former
Beginning data image；Or convert the image data of correction for attenuation, form non-correction for attenuation image.
Further, using ROI method or SUV value method, in human body18On F-FDG PET faultage image, each target is delineated
The region of interest of organ-tissue, system automatically form in region of interest18F-FDG tale, maximum count and average counter/
Pixel, using each target organ tissue of average counter/pixel extraction18F-FDG counting rate, each target organ group that will be extracted
It knits18F-FDG counting rate data, intromittent organ organizes uptake ratio computing module, after computer deducts background count automatically, meter
Calculate brain/cerebellum, cerebral white matter/cerebellum, other organs tissue/lung and lung/main organs (liver, kidney, marrow and bone
Flesh) ratio, these ratios are as each target organ tissue18F-FDG is summarized in database with respect to uptake ratio automatically.
Further, the tissue specificity DNA methylol background Primary parameter includes each target organ tissue dynamic DNA
Methylol background Primary parameter and each target organ tissue static state DNA methylol background Primary parameter；
Tissue specificity DNA methylol background secondary parameters include the various disease phases drawn for slow disease prevention and treatment and rehabilitation
It closes apparent gene phenotype chart and calculates relevant parameter；Each target organ tissue biological clock, environmental pressure, aging and health index
Analysis measurement；And it is calculated with the matching degree that DNA methylol context parameter finds various intervention means.
Further, each target organ tissue dynamic DNA methylol background Primary parameter measuring method is,
(S1) by each target organ tissue 18F-FDG uptake ratio input service module, system is automatically bent according to above-mentioned work
Line converts 18F-FDG uptake ratio to the DNA methylol age of each target organ tissue；
(S2) it averages to brain, cerebral white matter, lung, liver, kidney, marrow and skeletal muscle DNA methylol age,
Calculate each individual human DNA methylation age, i.e. epigenetic clock age；
(S3) the DNA methylol age of each target organ tissue is subtracted into actual age, calculates each target organ tissue automatically
DNA accelerate the aging age, the DNA of each target organ tissue accelerates aging age abbreviation DANhm AA；
(S4) everyone DNA methylation age is subtracted into actual age, the DNA acceleration for calculating everyone automatically declines
Old age.
Further, the tissue specificity DNA methylol background secondary parameters are carried on the back by tissue specificity DNA methylol
Scape Primary parameter derived method is,
Life expectancy=(it is expected that DNA methylation age at age -)+actual age；
Unhealthy index reference value is cancer patient's cohort brain DANhm AA, cerebral white matter DANhm AA, lung
DANhm AA, liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA average value multiplied by
Related coefficient 1；
Health index reference value is Normal Human Brain DANhm AA, cerebral white matter DANhm AA, lung DANhm AA, liver
DANhm AA, kidney DANhm AA, marrow DANhm AA, the average value of skeletal muscle DANhm AA are corresponding multiplied by cancer patient
Correlation coefficient value；
The inferior health index measurements relative of subject is cancer patient's cohort brain DANhm AA, cerebral white matter DANhm
The average value of AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA
Multiplied by the corresponding correlation coefficient value of cancer patient.
A kind of utilization18F-FDG PET molecular image data analysis measurement tissue specificity DNA methylol background method
Using applied to following field:
(H1) according to dynamic methylol background, the general level of the health, bimetry are assessed；
(H2) according to great slow sick characteristic methylol background, predict and prevent great chronic disease；
(H3) deviateed according to individual tissue specific DNA methylol static background, find methylation background and drug effect
Matching degree, individual instructions clinical application；
(H4) deviateed according to individual tissue specific DNA methylol static background, find methylation background and food activity
The matching degree of ingredient, instructs personalized nutritional；
(H5) deviateed according to individual tissue specific DNA methylol static background, find methylation background and sport and body-building
Matching degree and movement to health benefited intensity；
(H6) deviateed according to individual tissue specific DNA methylol static background, find methylation background and human-body biological
Bad life habits are corrected in the matching degree of clock coordination, personalization；
(H7) deviateed according to individual tissue specific DNA methylol static background, find methylation background and chronic low water
The matching degree of flat inflammatory reaction and the matching degree of calorie restriction effect carry out personalized anti-aging；
(H8) deviateed according to individual tissue specific DNA methylol static background, find methylation background and above situation
With the matching degree of other situations, it to be used for disease adjuvant treatment, rehabilitation, prenatal and postnatal care and health care.
Beneficial effects of the present invention are as described below: the present invention establishes a kind of non-invasive analysis measurement body tissue specificity
The method of DNA methylol background, overcomes that having for the prior art is traumatic, or the limitation of analysis measurement tissue quantity, can
Analysis measurement is carried out with the DNA methylol background to any normal organ tissue of whole body, and method is simple, strong operability,
It is easy to promote and utilize；The present invention can understand each organ-tissue gene molecule information for describing everyone, be clinician, strong
Health Contract Manager, nutritionist and researcher provide personalized molecular information and support；As long as original data transmissions are utilized this
The analysis measurement of the complete tissue specificity DNA methylol background of invention energy；The present invention is in clinical medicine, preventive medicine, health simultaneously
Multiple medicine and physical-fitness medicine field also have positive meaning.
Detailed description of the invention
Attached drawing 1 is the normal human tissue dynamic DNA methylation background directly measured and utilization 18F-FDG PET of the present invention
The normal human of data analysis measurement respectively organizes average dynamic DNA methylolation background to compare figure；
Attached drawing 2 is each tissue dynamic DNA methylation background of the cancer involvement directly measured and utilizes 18F- of the present invention
Each tissue average dynamic DNA methylolation background of the cancer involvement of FDG PET data analysis measurement compares figure；
Attached drawing 3 is after each tissue dynamic DNA methylation background of cancer patient decomposites, and directly measurement brain tissue is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement patient's brain tissue dynamic DNA methylolation back
Scape compares figure；
Attached drawing 4 is after each tissue dynamic DNA methylation background of cancer patient decomposites, directly to measure renal tissue
Dynamic DNA methylation background and present invention 18F-FDG PET data analysis measurement kidneys of patients tissue dynamic DNA methylol
Change background and compares figure；
Attached drawing 5 is after each tissue dynamic DNA methylation background of cancer patient decomposites, directly to measure lung tissue
Dynamic DNA methylation background and the present invention analyze measurement patient lungs with 18F-FDG PET data and organize dynamic DNA methylol
Change background and compares figure；
Attached drawing 6 is after each tissue dynamic DNA methylation background of cancer patient decomposites, directly to measure liver organization
Dynamic DNA methylation background and present invention 18F-FDG PET data analysis measurement patient's liver organization dynamic DNA methylol
Change background and compares figure；
Attached drawing 7 is after each tissue dynamic DNA methylation background of cancer patient decomposites, directly to measure myeloid tissue
Dynamic DNA methylation background and present invention 18F-FDG PET data analysis measurement Bone Marrow of Patients tissue dynamic DNA methylol
Change background and compares figure；
Attached drawing 8 is after each tissue dynamic DNA methylation background of cancer patient decomposites, directly to measure colonic tissue
Dynamic DNA methylation background and present invention 18F-FDG PET data analysis measurement subjects bones' muscular tissue dynamic DNA hydroxyl first
Base background compares figure；
Attached drawing 9 is after DNAm's age normal correction of cancer affected tissue to be methylated to, directly to measure brain tissue dynamic
DNA methylation background and present invention 18F-FDG PET data analysis measurement Normal Human Brain Tissue dynamic DNA methylolation back
Scape compares figure；
Attached drawing 10 is after DNAm's age normal correction of cancer affected tissue to be methylated to, and directly measurement renal tissue is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement Normal Renal tissue dynamic DNA methylol
Change background and compares figure；
Attached drawing 11 is after DNAm's age normal correction of cancer affected tissue to be methylated to, and directly measurement lung tissue is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement normal person lung tissue motion state DNA methylol
Change background and compares figure；
Attached drawing 12 is after DNAm's age normal correction of cancer affected tissue to be methylated to, and directly measurement liver organization is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement Normal Human Liver tissue dynamic DNA methylol
Change background and compares figure；
Attached drawing 13 is after DNAm's age normal correction of cancer affected tissue to be methylated to, and directly measurement myeloid tissue is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement Normal Human Bone Marrow tissue dynamic DNA methylol
Change background and compares figure；
Attached drawing 14 is after DNAm's age normal correction of cancer affected tissue to be methylated to, and directly measurement colonic tissue is dynamic
State DNA methylation background and present invention 18F-FDG PET data analysis measurement normal person's skeletal muscle tissue dynamic DNA hydroxyl first
Base background compares figure；
Attached drawing 15 is to decomposite normal organ tissue to come, brain DNA test and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 16 is to decomposite normal organ tissue to come, hepatic gene detection method and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 17 is to decomposite normal organ tissue to come, kidney DNA test and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 18 is to decomposite normal organ tissue to come, pulmonary gene detection method and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 19 is to decomposite normal organ tissue to come, marrow DNA test and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 20 is to decomposite normal organ tissue to come, and Skeletal Muscle Gene detection method and PET data of the present invention analysis are surveyed
Determine dynamic DNA methylolation background and compares figure；
Attached drawing 21 is to decomposite normal organ tissue to come, cerebellum DNA test and PET data of the present invention analysis measurement
Dynamic DNA methylolation background compares figure；
Attached drawing 22 is the operational module of each tissue specific DNA methylol background of 18F-FDG PET data analysis measurement；
Attached drawing 23 is that the tissue specificity DNA methylol background of the invention with the analysis measurement of 18F-FDG data deviates (a left side
Side) and directly measurement DNA methylation background deviation (right side).
Attached drawing 24 is the slow sick characteristic tissue DNA methylol background of present invention 18F-FDG PET data analysis measurement
Deviate schematic diagram；
Attached drawing 25 is bimetry length schematic diagram of the present invention.
Specific embodiment
The present invention will be further explained with reference to the accompanying drawing.
A kind of as described in attached drawing uses human body18F-FDG PET data analyzes tissue DNA methylol background, including following step
It is rapid:
(1) adult is obtained18F-FDG whole body faultage image；
(2) ROI method or SUV value method are used, the 18F-FDG data of each target tissue are extracted and calculates glucose uptake rate,
And it sets up and is corresponded to by Sex, Age18The database of F-FDG uptake ratio；
(3) it according to each target organ tissue database background of normal adult and its fitting, corrects DNA telomere and linearly shortens song
Line establishes the operational module of analysis measurement DNA methylol background；
(4) tissue specificity DNA methylol background Primary parameter is measured, and is sent by DNA methylol background Primary parameter
Born DNA methylol background secondary parameters.
In the present embodiment, using male's brain as research object, the operational module of analysis measurement DNA methylol background is established
As shown in Fig. 22, it sets up normal male brain 18F-FDG and absorbs rate database, as shown in curve A, and be fitted, it is such as bent
Shown in line B, closer to unanimously, Feasible degree is higher for database and fitting.Wherein curve C is that the shortening of Chinese DNA telomere is corresponding real
Border age linear attenuation curve, shortens decaying to DNA telomere with matched curve and is corrected, and forming curves D is used for DNA hydroxyl first
The analysis of base year age and dynamic methylol background measures: curve D is by ordinate male brain 18F-FDG uptake ratio and abscissa
The DNA methylol age corresponds, so that it may calculate individual brain DNA methylol age and team innovation DNA methylolation
Background.By the tissue specificity dynamic DNA methylol background of 18F-FDG PET data analysis measurement, directly measured with gene
Dynamic DNA methylation background is compared, and the two correlation is almost consistent, and the difference in detail is due to genetic test
Method measures dynamic DNA methylation background data and is derived from westerner, and the method for the present invention measurement is Chinese and research pair
The composition (especially the number total amounts and ratio of age groups) of elephant, mensuration methodology, using in standard and individual subject
Caused by many factors such as difference (such as smoking, excessive drinking, eating habit, treatment condition and cultural difference) are comprehensive.As attached drawing 20 to
Shown in 21,.In operational module, 18F-FDG PET can accurately analyze each age group DNA methylol age of measurement, and thus
The dynamic methylol background of composition, it was demonstrated that energy Accurate Determining individual of the present invention is made of the deviation of each organ-tissue DNA methylol
Static DNA methylol background.The target organ tissue quantity of measurement is more, and static DNA methylol background is more accurate.Working mould
In block, using shown in the curve E that -25 years old 18 years old DNA methylol backgrounds are standard such as in attached drawing 22, each organ-tissue 18F-FDG is taken the photograph
The bigger of rate and curve E deviation is taken, static DNA methylol background deviates bigger, compared with curve E, with the percentage of deviation
The DNA methylol background for calculating each target organ tissue deviates.Finally sketch out each individual human static state DNA methylol background such as
Shown in attached drawing 23, and by the static methylol background of personal static methylol background and normal person of the same age and cancer patient
It is compared, to judge the exact level that DNA methylol background deviates, as shown in Fig. 23, left figure I line is rejuvenation
DNA methylol background, directly measured relative to right side foetal DNA methylation background.Left figure J line is the various of cancer patient
Tissue DNA methylolation background, compared with rejuvenation background, the substantial deviation right path, relative to right side cancer cell DNA methylation
Substantial deviation occurs for background.Right-hand line L, be 55 years old control group DNA methylol background departure degree, based on normally with patient it
Between, respectively organize DNA methylation background to deviate between normally between cancer cell relative to right part of flg normal adult.Left-hand broken line
K is that the tissue specificity methylol background of 1 55 years old subject deviates situation.
Human body is obtained using Positron emission computed tomography instrument18The non-correction for attenuation raw-data map of F-FDG PET
Picture；Or convert the image data of correction for attenuation, form non-correction for attenuation image.
Using ROI method or SUV value method, in human body18On F-FDG PET faultage image, each target organ tissue is delineated
Region of interest, system automatically form in region of interest18F-FDG tale, maximum count and average counter/pixel, using flat
Counting/pixel extraction each target organ tissue18F-FDG counting rate, by each target organ tissue extracted18F-FDG
Counting rate data, intromittent organ organizes uptake ratio computing module, after computer deducts background count automatically, calculates brain/small
Brain, cerebral white matter/cerebellum, other organs tissue/lung and lung/main organs (liver, kidney, marrow and skeletal muscle) ratio, this
A little ratios are as each target organ tissue18F-FDG is summarized in database with respect to uptake ratio automatically.
The tissue specificity DNA methylol background Primary parameter includes each target organ tissue dynamic DNA methylol background
Primary parameter and each target organ tissue static state DNA methylol background Primary parameter；
Tissue specificity DNA methylol background secondary parameters include the various disease phases drawn for slow disease prevention and treatment and rehabilitation
It closes apparent gene phenotype chart and calculates relevant parameter；Each target organ tissue biological clock, environmental pressure, aging and health index
Analysis measurement；And it is calculated with the matching degree that DNA methylol context parameter finds various intervention means.
Each target organ tissue dynamic DNA methylol background Primary parameter measuring method is,
(S1) by each target organ tissue 18F-FDG uptake ratio input service module, system is automatically bent according to above-mentioned work
Line converts 18F-FDG uptake ratio to the DNA methylol age of each target organ tissue；
(S2) it averages to brain, cerebral white matter, lung, liver, kidney, marrow and skeletal muscle DNA methylol age,
Calculate each individual human DNA methylation age, i.e. epigenetic clock age；
(S3) the DNA methylol age of each target organ tissue is subtracted into actual age, calculates each target organ tissue automatically
DNA accelerate the aging age, the DNA of each target organ tissue accelerates aging age abbreviation DANhm AA；
(S4) everyone DNA methylation age is subtracted into actual age, the DNA acceleration for calculating everyone automatically declines
Old age.
The tissue specificity DNA methylol background secondary parameters are by tissue specificity DNA methylol background Primary parameter
Derived method are as follows:
Life expectancy=(it is expected that DNA methylation age at age -)+actual age；As shown in Fig. 24, wherein F Qu Weichang
Longevity area, in long-lived region, female ratio's highest accounts for 26%；Cancer patient's ratio is very low, and only 2.8%；The region G is service life contracting
Short area, female ratio is minimum to account for 20.1%；Cancer patient's ratio highest accounts for 40.5%；Illustrate 1 subject, male 55 years old,
The DNA methylol age accelerates to be -3.2 years old, is located at Changshou District.
DNA methylol age acceleration figure is drawn, personal position is marked on wherein, it is intuitive to show life expectancy feelings
Condition, as shown in Fig. 24.The DNA methylolation background departure degree and chart of each target organ tissue represent each individual tissue
Specific static state DNA methylolation background, and the individual background that will test and 25 years old young state methylol background, contemporary
Methylol background, cancer patient's methylol background compare and analyze.The background of measurement deviates result and directly measures DNA first
It is consistent that baseization deviates result.
Unhealthy index reference value is cancer patient's cohort brain DANhm AA, cerebral white matter DANhm AA, lung
DANhm AA, liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA average value multiplied by
Related coefficient 1；
Health index reference value is Normal Human Brain DANhm AA, cerebral white matter DANhm AA, lung DANhm AA, liver
DANhm AA, kidney DANhm AA, marrow DANhm AA, the average value of skeletal muscle DANhm AA are corresponding multiplied by cancer patient
Correlation coefficient value；
The inferior health index measurements relative of subject is cancer patient's cohort brain DANhm AA, cerebral white matter DANhm
The average value of AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA
Multiplied by the corresponding correlation coefficient value of cancer patient.
The measurement and calculating of each target organ tissue static state DNA methylol background Primary parameter:
DNAhm rejuvenation background value refers to -25 years old 18 years old age groups, and the 18F-FDG of normal each target organ tissue averagely takes the photograph
Rate is taken, the rejuvenation DNA methylol levels of target organ tissue are represented；
DNAhm deviates critical value, refers to that the 18F-FDG of each target organ tissue of all cancer patients be averaged uptake ratio, representative
The DNA methylol substantial deviation of target organ tissue is horizontal；
DNAhm deviates desired value, refers to that the 18F-FDG of each target organ tissue of same age group normal person be averaged uptake ratio, representative
The DNA methylol average departure of target organ tissue is horizontal；
DNAhm deviates measured value, refers to the 18F-FDG uptake ratio of each target organ tissue of subject, represents subject's target organ
The DNA methylol of tissue deviates horizontal；
Methylol background deviates critical value, refers to brain, cerebral white matter, heart, lung, liver, the kidney of all cancer patients
The average value that dirty, skeletal muscle and marrow DNA methylol background deviate；
Methylol background deviates desired value, refers to brain, cerebral white matter, heart, lung, liver, the kidney of cohort normal person
The average value that dirty, skeletal muscle and marrow DNA methylol background deviate；
Methylol background deviation index refers to brain, cerebral white matter, heart, lung, liver, kidney, the skeletal muscle of subject
The measured value deviateed with marrow DNA methylol background；
Methylol background deviates measured value, refers to brain, cerebral white matter, heart, lung, liver, kidney, the bone of subject
The average value of flesh and marrow DNA methylol background deviation index；
Methylolation departure degree refers to that each target organ tissue and -25 years old 18 years old age group rejuvenation background values compare, hydroxyl first
The percentage that baseization deviates, percentage is bigger, and background deviates more serious.
The calculating of the tissue specificity DNA methylol background secondary parameters:
Biological clock Coordination index, for measuring biological clock master clock cerebral white matter, with peripheral tissues clock (brain, liver, kidney
Dirty, skeletal muscle and adrenal gland) DNA methylol background harmony, calculate cerebral white matter methylol levels and brain, liver, kidney
The difference of dirty, skeletal muscle, adrenal gland methylol levels, the size of standard deviation, represents the good of biological clock harmony between each difference
Bad, i.e., standard deviation is bigger, and biological clock harmony is better；On the contrary, standard deviation is smaller, biological clock harmony is poorer；
Risk of cancer index and risk score are carried on the back according to the characteristic methylol of the cancer patient of this patent method measurement
Scape, as shown in figure FIG6, the first target organs of methylol substantial deviation are brain, cerebral white matter, liver, kidney and bone respectively
Bone flesh, and according to departure degree, sort brain (weight 1)=cerebral white matter (weight 1) > liver (weight 0.9)=kidney (power
Weigh 0.9) > skeletal muscle (weight 0.7).Therefore, risk of cancer index=brain weight/brain 18F-FDG uptake ratio+brain is white
3/ liver 18F-FDG uptake ratio of mortgage weight/cerebral white matter 18F-FDG uptake ratio+liver weight *+3/ kidney of kidney weight *
18F-FDG uptake ratio+skeletal muscle weight/skeletal muscle 18F-FDG uptake ratio.Risk score=(subject's risk of cancer index/
Cancer patient's risk of cancer index) * 100%, be greater than 85% (85 points) be cancer high risk；
Senile neurological systemic disease risk index and risk score, the old nervous system measured according to this patent method
Property disease characteristic methylol background, if figure FIG6 shown in, the first target organs of methylol substantial deviation, according to deviate journey
Degree sequence liver (weight 0.8)=kidney (weight 0.8)=marrow (weight 0.8) > brain (weight 0.7)=cerebral white matter (power
Weigh 0.7) > skeletal muscle (weight 0.6).Therefore, old the nervous system disease risk index=brain weight/brain 18F-FDG takes the photograph
Take 3/ liver 18F-FDG uptake ratio of rate+cerebral white matter weight/cerebral white matter 18F-FDG uptake ratio+liver weight *+kidney power
3/ kidney 18F-FDG uptake ratio of weight *+skeletal muscle weight/skeletal muscle 18F-FDG uptake ratio.Risk score=(subject is old
The nervous system disease risk index/old age patient with nervous system disease risk index) * 100%, it is old for being greater than 87% (87 points)
Year nerve systemic disease high risk；
Diabetes risk index and risk score are carried on the back according to the characteristic methylol of the diabetes of this patent method measurement
Scape, as figure FIG6 shown in, the first target organs of methylol substantial deviation, according to departure degree sequence skeletal muscle (weight 0.9) >
Kidney (weight 0.8) > liver (weight 0.7)=marrow (weight 0.7) > brain (weight 0.6)=cerebral white matter (weight 0.6) >
Skeletal muscle (weight 0.6), therefore, diabetes risk index=brain weight/brain 18F-FDG uptake ratio+cerebral white matter power
3/ liver 18F-FDG uptake ratio of weight/cerebral white matter 18F-FDG uptake ratio+liver weight *+3/ kidney 18F-FDG of kidney weight *
Uptake ratio+skeletal muscle weight/skeletal muscle 18F-FDG intake, risk score=(sub-ject's risk index/patient of diabetes
Person's risk index) * 100%, be greater than 85% (85 points) be diabetes risk；
Environmental pressure index reflects nerve immunity system function state, constructs unique brain, adrenal gland, spleen and disappear
Change road (colon) methylol background characteristics.Therefore, environmental pressure index=(adrenal gland 18F-FDG uptake ratio+spleen 18F-FDG
Uptake ratio+colon 18F-FDG uptake ratio)/brain 18F-FDG uptake ratio, environmental pressure index health value, critical value, control value
- 25 years old 18 years old age groups, cancer patient's group, cohort and the environmental pressure index value of subject are respectively represented with measured value；
Low-level inflammation series connection index, is very important aging index and disease risks index, there is intestinal flora to lose
It adjusts and skeletal muscle, liver and the concatenated apparent gene variation characteristic of brain.Therefore, low-level inflammation series connection index=colon
18F-FDG uptake ratio/(skeletal muscle 18F-FDG uptake ratio+liver 18F-FDG uptake ratio+brain 18F-FDG uptake ratio).Low water
Flat inflammation series connection index health value, critical value, control value and measured value respectively represent -25 years old 18 years old age groups, cancer patients
Group, cohort and the environmental pressure index of subject value；
The calculating of the tissue specificity DNA methylol background secondary parameters matching degree:
Deviateed according to individual tissue specific DNA methylol static background, it is pharmaceutically-active with certain to find methylation background
Matching degree, individual instructions clinical application: drug effect degree and each target organ DNA of the matching degree=drug effect in each target tissue
Degree of relevancy between methylol background departure degree.For positive correlation coefficient between 0 to 1, relative coefficient is bigger, drug
Bigger to the toxicity of subject, side effect is bigger；For negative correlation coefficient between 0 to -1, relative coefficient is bigger, drug to by
The toxicity of examination person is smaller, and side effect is smaller.
According to individual tissue specific DNA methylol static background deviate, find methylation background and certain food activity at
The matching degree divided, instruct personalized nutritional: matching degree=nutrient substance improves the DNA methylation background journey of each target tissue
Degree of relevancy between degree and each target organ DNA methylol background departure degree.Positive correlation coefficient is related between 0 to 1
Property coefficient is bigger, and the nutrient and healthcare products are better to the effect of subject；Negative correlation coefficient between 0 to -1, get over by relative coefficient
Greatly, the health nutrient is to subject more without effect.
Deviateed according to individual tissue specific DNA methylol static background, finds of methylation background and sport and body-building
With degree and move the benefited intensity to health: matching degree=sport and body-building can improve the DNA methylation background severity of each target tissue
With the degree of relevancy between each target organ DNA methylol background departure degree.Positive correlation coefficient is between 0 to 1, correlation
Coefficient is bigger, and sport and body-building is more beneficial to subject.
Deviateed according to individual tissue specific DNA methylol static background, finds methylation background and biological clock is assisted
Bad life habits are corrected in the matching degree of tune, personalization: matching degree=bad life habits influence the DNA methyl of each target tissue
Change the degree of relevancy between background severity and each target organ DNA methylol background departure degree.Positive correlation coefficient 0 to 1 it
Between, relative coefficient is bigger, and bad life habits are bigger to the injury of subject.
Deviateed according to individual tissue specific DNA methylol static background, finds methylation background and calorie restriction effect
Matching degree, carry out personalized anti-aging: matching degree=calorie limitation improves the DNA methylation background severity of each target tissue
With the degree of relevancy between each target organ DNA methylol background departure degree.Positive correlation coefficient is between 0 to 1, correlation
Coefficient is bigger, and calorie is limited to the benefited bigger of subject.
Deviateed according to individual tissue specific DNA methylol static background, finds methylation background and great chronic disease
The matching degree for the background that methylates, carries out personalized prevention disease: matching degree=various diseases DNA methylation background and each
Degree of relevancy between target organ DNA methylol background departure degree.Positive correlation coefficient is between 0 to 1, relative coefficient
Bigger, the risk of illness is bigger.
Deviateed according to individual tissue specific DNA methylol static background, finds methylation background and above situation and its
The matching degree of his situation, calculation method is the same, is used for disease adjuvant treatment, rehabilitation, prenatal and postnatal care and health care.
A kind of utilization18F-FDG PET molecular image data analysis measurement tissue specificity DNA methylol background method
Applied to following field:
(H1) according to dynamic methylol background, the general level of the health, bimetry are assessed；
(H2) according to great slow sick characteristic methylol background, predict and prevent great chronic disease；
(H3) deviateed according to individual tissue specific DNA methylol static background, find methylation background and drug effect
Matching degree, individual instructions clinical application；
(H4) deviateed according to individual tissue specific DNA methylol static background, find methylation background and food activity
The matching degree of ingredient, instructs personalized nutritional；
(H5) deviateed according to individual tissue specific DNA methylol static background, find methylation background and sport and body-building
Matching degree and movement to health benefited intensity；
(H6) deviateed according to individual tissue specific DNA methylol static background, find methylation background and human-body biological
Bad life habits are corrected in the matching degree of clock coordination, personalization；
(H7) deviateed according to individual tissue specific DNA methylol static background, find methylation background and chronic low water
The matching degree of flat inflammatory reaction and the matching degree of calorie restriction effect carry out personalized anti-aging；
(H8) deviateed according to individual tissue specific DNA methylol static background, find methylation background and above situation
With the matching degree of other situations, it to be used for disease adjuvant treatment, rehabilitation, prenatal and postnatal care and health care.
The above is only a preferred embodiment of the present invention, it should be pointed out that: for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications
It should be regarded as protection scope of the present invention.
Claims (7)
1. a kind of use human body18F-FDG PET data analyzes tissue DNA methylol background, it is characterised in that the following steps are included:
(1) adult is obtained18F-FDG whole body faultage image；
(2) ROI method or SUV value method are used, the 18F-FDG data of each target tissue are extracted and calculates glucose uptake rate, and group
It builds and is corresponded to by Sex, Age18The database of F-FDG uptake ratio；
(3) it according to each target organ tissue database background of normal adult and its fitting, corrects DNA telomere and linearly shortens curve, build
The operational module of vertical analysis measurement DNA methylol background；
(4) tissue specificity DNA methylol background Primary parameter and tissue specificity DNA methylol background second level ginseng are measured
Number.
2. a kind of human body is used according to claim 118F-FDG PET data analyzes tissue DNA methylol background, feature
It is: obtains human body using Positron emission computed tomography instrument18The non-correction for attenuation initial data image of F-FDG PET；
Or convert the image data of correction for attenuation, form non-correction for attenuation image.
3. a kind of human body is used according to claim 118F-FDG PET data analyzes tissue DNA methylol background, feature
It is: using ROI method or SUV value method, in human body18On F-FDG PET faultage image, the sense for delineating each target organ tissue is emerging
Interesting area, system automatically form in region of interest18F-FDG tale, maximum count and average counter/pixel, using average meter
Each target organ tissue of number/pixel extraction18F-FDG counting rate, by each target organ tissue extracted18F-FDG counting rate
Data, intromittent organ organizes uptake ratio computing module, after computer deducts background count automatically, calculates brain/cerebellum, brain
White matter/cerebellum, other organs tissue/lung and lung/main organs (liver, kidney, marrow and skeletal muscle) ratio, these ratios are made
For each target organ tissue18F-FDG is summarized in database with respect to uptake ratio automatically.
4. a kind of human body is used according to claim 118F-FDG PET data analyzes tissue DNA methylol background, feature
Be: the tissue specificity DNA methylol background Primary parameter includes each target organ tissue dynamic DNA methylol background level-one
Parameter and each target organ tissue static state DNA methylol background Primary parameter；
Tissue specificity DNA methylol background secondary parameters include the various disease correlation tables drawn for slow disease prevention and treatment and rehabilitation
It sees gene phenotype chart and calculates relevant parameter；Each target organ tissue biological clock, environmental pressure, aging and health index analysis
Measurement；And it is calculated with the matching degree that DNA methylol context parameter finds various intervention means.
5. a kind of human body is used according to claim 418F-FDG PET data analyzes tissue DNA methylol background, feature
Be: each target organ tissue dynamic DNA methylol background Primary parameter measuring method is,
(S1) by each target organ tissue 18F-FDG uptake ratio input service module, system, will automatically according to above-mentioned working curve
18F-FDG uptake ratio is converted into the DNA methylol age of each target organ tissue；
(S2) it averages, calculates to brain, cerebral white matter, lung, liver, kidney, marrow and skeletal muscle DNA methylol age
Each individual human DNA methylation age, i.e. epigenetic clock age；
(S3) the DNA methylol age of each target organ tissue is subtracted into actual age, calculates the DNA of each target organ tissue automatically
Accelerate the aging age, the DNA of each target organ tissue accelerates aging age abbreviation DANhm AA；
(S4) everyone DNA methylation age is subtracted into actual age, the DNA for calculating everyone automatically accelerates aging year
Age.
6. a kind of human body is used according to claim 518F-FDG PET data analyzes tissue DNA methylol background, feature
Be: the tissue specificity DNA methylol background secondary parameters are derived from by tissue specificity DNA methylol background Primary parameter
Method is,
Life expectancy=(it is expected that DNA methylation age at age -)+actual age；
Unhealthy index reference value be cancer patient's cohort brain DANhm AA, cerebral white matter DANhm AA, lung DANhm AA,
Liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA average value multiplied by related coefficient 1；
Health index reference value is Normal Human Brain DANhm AA, cerebral white matter DANhm AA, lung DANhm AA, liver DANhm
AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA average value multiplied by the corresponding phase relation of cancer patient
Numerical value；
The inferior health index measurements relative of subject is cancer patient's cohort brain DANhm AA, cerebral white matter DANhm AA, lung
DANhm AA, liver DANhm AA, kidney DANhm AA, marrow DANhm AA, skeletal muscle DANhm AA average value multiplied by
The corresponding correlation coefficient value of cancer patient.
7. a kind of use human body18F-FDG PET data analysis tissue DNA methylol background application, it is characterised in that be applied to
Lower field:
(H1) according to dynamic methylol background, the general level of the health, bimetry are assessed；
(H2) according to great slow sick characteristic methylol background, predict and prevent great chronic disease；
(H3) deviateed according to individual tissue specific DNA methylol static background, find methylation background and pharmaceutically-active
With degree, individual instructions clinical application；
(H4) deviateed according to individual tissue specific DNA methylol static background, find methylation background and food active constituent
Matching degree, instruct personalized nutritional；
(H5) deviateed according to individual tissue specific DNA methylol static background, find of methylation background and sport and body-building
With degree and move the benefited intensity to health；
(H6) deviateed according to individual tissue specific DNA methylol static background, find methylation background and biological clock is assisted
Bad life habits are corrected in the matching degree of tune, personalization；
(H7) deviateed according to individual tissue specific DNA methylol static background, find methylation background and chronic low level is scorching
The matching degree of disease reaction and the matching degree of calorie restriction effect, carry out personalized anti-aging；
(H8) deviateed according to individual tissue specific DNA methylol static background, find methylation background and above situation and its
The matching degree of his situation is used for disease adjuvant treatment, rehabilitation, prenatal and postnatal care and health care.
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