CN109979598B - By human body18F-FDG PET data analysis tissue DNA hydroxymethyl background and application - Google Patents
By human body18F-FDG PET data analysis tissue DNA hydroxymethyl background and application Download PDFInfo
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Abstract
The invention discloses a human body18F-FDG PET data analysis tissue DNA hydroxymethyl background and application thereof, including acquisition of adult18F-FDG whole body tomograms; extracting 18F-FDG data of each target tissue, calculating glucose uptake rate, and establishing sex-based age correspondence18A database of F-FDG uptake rates; correcting a DNA telomere linear shortening curve according to the background of each target organ tissue database of the normal adult and the fitting of the background, and establishing a working module for analyzing and determining the background of DNA hydroxymethyl; determining a tissue-specific DNA hydroxymethyl background primary parameter and a tissue-specific DNA hydroxymethyl background secondary parameter. The invention provides a method for non-invasive analysis and determination of the whole body tissue specific DNA hydroxymethyl background, which can provide effective gene molecular information support for individualized prevention and cure and rehabilitation of chronic diseases, individualized health care and health maintenance and accurate medical research and development.
Description
Technical Field
The invention relates to the field of medical biology and major health, in particular to a human body18F-FDG PET data analysis tissue DNA hydroxymethyl background and application.
Background
Major chronic diseases, which have become major threats to human health, mainly include cardiovascular and cerebrovascular diseases, cancer, chronic respiratory diseases, diabetes and oral diseases, and endocrine, renal, skeletal and neurological diseases.
The causes of major chronic diseases are attributed to the adverse environment in and out of the human body, including cellular senescence, harmful substances, inflammatory factors, poor lifestyle, unscientific nutrition, lack of exercise and environmental stress, etc. in 80%. And epigenomes (sets) are the bridge between the environment and chronic disease. The off-track tissue-specific gene methylation background is a characteristic manifestation of epigenetic abnormalities, and the gene methylation background is already abnormal years or even decades before the disease occurs. The background abnormality of gene methylation causes various gene expression abnormalities, not only can affect health and life, but also can cause cardiovascular and cerebrovascular diseases, diabetes and nervous system diseases, and can also cause gene instability, gene mutation and silence of cancer suppressor genes, thereby being an important reason for inducing cancer and promoting tumor recurrence and metastasis. Because the cell aging part, range and degree of each person are different, and the adverse environmental conditions inside and outside the body are different, the different tissue-specific gene methylation background of each person is created. Only by mastering the individual characteristics of the epigenetic genes of each person, the individual intervention on health and diseases can be effectively carried out, so that the morbidity and mortality of major chronic diseases are effectively reduced, and the total goals of improving the health level and promoting the longevity are finally achieved.
At present, various methods for detecting DNA methylation background have been developed at home and abroad, wherein noninvasive detection can be realized through blood cells and salivary cells. However, because the difference of each tissue cell in the organism is large, and the effect of the environment on the target organs of the human body is different, the detection means of the single cell or the single tissue cannot achieve the purpose of describing the DNA methylation background of the whole human body in a non-invasive way. In recent years, numerous studies have shown that glucose uptake by body cells is closely linked to the DNA hydroxymethyl background on many signaling pathways. Thus making use of18F-FDG PET molecular image data analysis determines tissue-specific DNA, thereby overcoming the defects of the existing method for detecting DNA methylation background.
Disclosure of Invention
The purpose of the invention is as follows: in order to overcome the defects in the prior art, the invention provides a novel anti-counterfeiting bottle18The background method for analyzing and determining tissue-specific DNA (deoxyribonucleic acid) hydroxymethyl by F-FDG PET (positron emission tomography) molecular image data and the application thereof are used for effectively and feasibly developing and utilizing human genetic information, overcoming the defects in the existing DNA methylation background analysis and determination technology, and simultaneously providing human genetic molecular data, technical support, personalized health consultation and guidance for personalized chronic disease prevention and recovery, personalized health care and health preservation, health promotion and longevity.
The technical scheme is as follows: to achieve the above object, an application of the present invention18Method for analyzing and determining tissue-specific DNA hydroxymethyl background by F-FDG PET molecular image data, without biopsy tissue specimen extraction, by extracting tissue of any target organ18F-FDG PET image data, and the glucose uptake rate of each target organ tissue is calculated, and the background information of each organ tissue gene methylation of each person can be more comprehensively mastered through the analysis module established by the invention. The method comprises the following steps:
(1) obtaining adults18F-FDG whole body tomograms;
(2) extracting each target tissue by ROI method or SUV value method18F-FDG data and calculating glucose uptake and establishing chronological age correspondence18A database of F-FDG uptake rates;
(3) correcting a DNA telomere linear shortening curve according to the background of each target organ tissue database of the normal adult and the fitting of the background, and establishing a working module for analyzing and determining the background of DNA hydroxymethyl;
(4) determining a tissue-specific DNA hydroxymethyl background primary parameter and a tissue-specific DNA hydroxymethyl background secondary parameter.
Further, the positron emission computed tomography scanner is used for acquiring the human body18F-FDG PET non-attenuation correction original data image; or the attenuation-corrected image data is converted to form a non-attenuation-corrected image.
Further, the ROI method or SUV value method is used in human body18The interested region of each target organ tissue is outlined on the F-FDG PET sectional image, and the system automatically forms the interested region18F-FDG total count, maximum count and average count/pixel, and extracting the tissue of each target organ by using the average count/pixel18F-FDG count rate of each target organ tissue to be extracted18F-FDG count rate data is input into an organ tissue uptake rate calculation module, the computer automatically deducts background count, and then calculates the ratios of brain/cerebellum, white matter/cerebellum of brain, other organ tissues/lung and lung/main organs (liver, kidney, bone marrow and skeletal muscle) which are used as the ratio of each target organ tissue18F-FDG relative uptake and was automatically summarized in the database.
Further, the tissue-specific DNA hydroxymethyl background primary parameters comprise dynamic DNA hydroxymethyl background primary parameters of each target organ tissue and static DNA hydroxymethyl background primary parameters of each target organ tissue;
the tissue-specific DNA hydroxymethyl background secondary parameters comprise a table chart for drawing various disease-related epigenotypes for chronic disease prevention and rehabilitation and calculation related parameters; analyzing and measuring biological clock, environmental stress, aging and health index of each target organ and tissue; and matching degree calculation for searching various intervention means by using the background parameters of DNA hydroxymethyl.
Furthermore, the method for measuring the first-level parameters of the dynamic DNA hydroxymethyl background of each target organ tissue comprises the following steps,
(S1) treating the target organ tissues18The F-FDG uptake rate is input into a working module, and the system automatically adjusts the F-FDG uptake rate according to the working curve18The F-FDG uptake rate is converted into the DNA hydroxymethyl age of each target organ tissue;
(S2) averaging the age of hydroxymethyl in DNA of brain, white matter of brain, lung, liver, kidney, bone marrow and skeletal muscle, and calculating the age of DNA methylation of each individual, i.e. the age of epigenetic clock;
(S3) subtracting the actual age from the hydroxymethyl age of the DNA of each target organ tissue, and automatically calculating the accelerated aging age of the DNA of each target organ tissue, wherein the accelerated aging age of the DNA of each target organ tissue is called as DANhm AA for short;
(S4) the age for accelerating aging of DNA of each person is automatically calculated by subtracting the actual age from the age for methylating DNA of each person.
Furthermore, the derivation method of the tissue-specific DNA hydroxymethyl background secondary parameter from the tissue-specific DNA hydroxymethyl background primary parameter is that,
life expectancy ═ (age expected-age of DNA methylation) + actual age;
the unhealthy index reference value is the average value of brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA of the age group of the cancer patient and then multiplied by a correlation coefficient 1;
the health index reference value is the average value of normal human brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA, and then multiplied by the corresponding correlation coefficient value of the cancer patient;
the sub-health index of the subject is determined by averaging the brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA, and skeletal muscle DANhm AA of the age group of the cancer patient and multiplying the average by the corresponding correlation coefficient value of the cancer patient.
Use of18The application of the background method for analyzing and determining tissue-specific DNA hydroxymethyl by F-FDG PET molecular image data is applied to the following fields:
(H1) evaluating health level and predicting life according to dynamic hydroxymethyl background;
(H2) predicting and preventing major chronic diseases according to the characteristic hydroxymethyl background of the major chronic diseases;
(H3) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the drug action is searched, and the clinical medication is guided in a personalized way;
(H4) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the food active ingredients is searched, and personalized nutrition is guided;
(H5) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the exercise fitness and the benefit degree of the exercise on the health are searched;
(H6) according to the deviation of the static background of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the human body biological clock is searched, and the bad living habits are corrected in a personalized manner;
(H7) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the chronic low-level inflammatory reaction and the matching degree of the thermal card limiting effect are searched for, and personalized anti-aging is carried out;
(H8) according to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background with the situations and other situations is searched for the disease auxiliary treatment, the disease rehabilitation, the prenatal and postnatal care and the health care.
The beneficial effects of the invention are as follows: the invention establishes a method for non-invasive analysis and determination of the DNA hydroxymethyl background of the tissue specificity of the whole body, overcomes the defects of the prior art that the tissue specificity is traumatic or the limitation of analysis and determination of the number of tissues is limited, can analyze and determine the DNA hydroxymethyl background of any normal organ tissue of the whole body, and has the advantages of simple method, strong operability and convenient popularization and application; the invention can clearly depict the molecular information of each organ and tissue gene of each person, and provides personalized molecular information support for clinicians, health managers, dieticians and researchers; the invention can complete the analysis and determination of the tissue-specific DNA hydroxymethyl background only by transmitting the original data; meanwhile, the invention also has positive significance in the fields of clinical medicine, preventive medicine, rehabilitation medicine and health care medicine.
Drawings
FIG. 1 is a background of dynamic DNA methylation of normal human tissue directly measured and using the present invention18F-FDG PET data analysis and determination of the background comparison graph of the average dynamic DNA hydroxymethylation of each tissue of a normal human body;
FIG. 2 is a background of dynamic DNA methylation of cancer-affected tissues directly determined and utilizing the present invention18A background comparison graph of mean dynamic DNA hydroxymethylation of tissues affected by cancer as determined by F-FDG PET data analysis;
FIG. 3 shows the direct determination of the background of brain tissue dynamic DNA methylation after the background of tissue dynamic DNA methylation of cancer patients is resolved and the invention is applied18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of brain tissues of the patient;
FIG. 4 is a graph showing the direct determination of the dynamic background of DNA methylation in renal tissue after the dynamic background of DNA methylation in various tissues of a cancer patient is resolved, and the present invention is used in18F-FDG PET data analysis is carried out to determine a dynamic DNA hydroxymethylation background comparison graph of the kidney tissues of the patient;
FIG. 5 shows the direct determination of the dynamic DNA methylation background of lung tissue after the dynamic DNA methylation background of each tissue of cancer patients is resolved, and the invention is applied18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of lung tissues of a patient;
FIG. 6 shows the direct determination of liver tissue dynamic DNA methylation background after the dynamic DNA methylation background of each tissue of cancer patients is resolved, and the invention is applied18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of liver tissues of the patient;
FIG. 7 shows dynamic DNA methylation of various tissues of cancer patientsAfter the background is decomposed, the dynamic DNA methylation background of the bone marrow tissue is directly measured and used in the invention18F-FDG PET data analysis is used for determining a background comparison graph of dynamic DNA (deoxyribonucleic acid) hydroxymethylation of bone marrow tissues of the patient;
FIG. 8 is a graph showing the direct determination of the background of dynamic DNA methylation in colon tissue after the background of dynamic DNA methylation in various tissues of cancer patients is resolved, and the invention is applied to18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of skeletal muscle tissues of the patient;
FIG. 9 is a graph showing the direct determination of the background of dynamic DNA methylation in brain tissue after correcting the age of methylation of DNAm from cancer-affected tissues to be normal and use in accordance with the invention18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of normal human brain tissues;
FIG. 10 is a graph showing the direct determination of the background of dynamic DNA methylation in renal tissue after correcting the age of methylation of DNAm in cancer-affected tissues for normal age and use in accordance with the invention18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of normal human kidney tissues;
FIG. 11 is a graph showing the direct determination of the background of dynamic DNA methylation in lung tissue after correcting the age of methylation of DNAm from cancer-affected tissues to be normal and use in accordance with the invention18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of normal human lung tissues;
FIG. 12 is a graph showing the direct determination of the background of dynamic DNA methylation in liver tissue after correcting the age of methylation of DNAm from cancer affected tissues to be normal and use in accordance with the present invention18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of normal human liver tissues;
FIG. 13 is a graph showing the direct determination of the background of dynamic DNA methylation in bone marrow tissue after correcting the age of methylation of DNAm in cancer-affected tissues to be normal and use in accordance with the invention18F-FDG PET data analysis is carried out to determine a background comparison graph of dynamic DNA hydroxymethylation of normal human bone marrow tissues;
FIG. 14 is a graph showing the direct determination of the background of dynamic DNA methylation in colon tissue after correcting the age of methylation of DNAm from cancer-affected tissues to be normal and use in accordance with the invention18Analysis and determination of Normal human skeletal muscle tissue by F-FDG PET dataA background comparison graph of dynamic DNA hydroxymethylation;
FIG. 15 is a background comparison chart of dynamic DNA hydroxymethylation measured by a brain gene detection method and the PET data analysis of the present invention, with normal organ tissues decomposed;
FIG. 16 is a background comparison chart of the liver gene detection method with the dynamic DNA hydroxymethylation determined by the PET data analysis of the present invention, with normal organ tissues decomposed;
FIG. 17 is a background comparison chart of the renal gene detection method with the dynamic DNA hydroxymethylation determined by the PET data analysis of the present invention, with normal organ tissues decomposed;
FIG. 18 is a background comparison chart of the lung gene detection method with the analysis and determination of dynamic DNA hydroxymethylation by the PET data of the present invention, with normal organ tissues decomposed;
FIG. 19 is a background comparison graph of a bone marrow gene assay with dynamic DNA hydroxymethylation determined by the PET data analysis of the present invention, with normal organ tissue broken down;
FIG. 20 is a background comparison chart of the skeletal muscle gene detection method with the dynamic DNA hydroxymethylation determined by the PET data analysis of the present invention, with normal organ tissues decomposed;
FIG. 21 is a background comparison chart of dynamic DNA hydroxymethylation measured by a cerebellar gene detection method and the PET data analysis of the present invention, in which normal organ tissues are decomposed;
FIG. 22 is a drawing of18A working module for analyzing and determining the hydroxymethyl background of each tissue-specific DNA by using F-FDG PET data;
FIG. 23 is a drawing for illustrating the use of the present invention18Analysis of F-FDG data determined for tissue-specific DNA hydroxymethyl background bias (left) and direct determination of DNA methylation background bias (right).
FIG. 24 is a drawing of a sheet for carrying out the invention18Deviation from the schematic diagram of DNA hydroxymethyl background of chronic disease characteristic tissues determined by F-FDG PET data analysis;
FIG. 25 is a schematic diagram of the life prediction according to the present invention.
Detailed Description
The present invention will be further described with reference to the accompanying drawings.
Such as attachOne kind of figure is described18F-FDG PET data analysis of tissue DNA hydroxymethyl background, comprising the steps of:
(1) obtaining adults18F-FDG whole body tomograms;
(2) extracting each target tissue by ROI method or SUV value method18F-FDG data and calculating glucose uptake and establishing chronological age correspondence18A database of F-FDG uptake rates;
(3) correcting a DNA telomere linear shortening curve according to the background of each target organ tissue database of the normal adult and the fitting of the background, and establishing a working module for analyzing and determining the background of DNA hydroxymethyl;
(4) determining a tissue-specific DNA hydroxymethyl background primary parameter, and deriving a DNA hydroxymethyl background secondary parameter from the DNA hydroxymethyl background primary parameter.
In this example, a working module for analyzing and determining the background of DNA hydroxymethyl was constructed by using a male brain as a study subject, as shown in fig. 22, to construct a normal male brain18And F-FDG uptake rate database is shown as a curve A and is fitted, and as shown as a curve B, the closer the database is to the fit, the higher the feasibility degree is. Wherein the curve C is a linear attenuation curve corresponding to the actual age of the Chinese DNA telomere shortening, and the attenuation of the DNA telomere shortening is corrected by using a fitting curve to form a curve D for analyzing and determining the DNA hydroxymethyl age and the dynamic hydroxymethyl background: curve D ordinate Male cerebrum18The F-FDG uptake rate and the DNA hydroxymethyl age on the abscissa correspond to each other one by one, so that the individual brain DNA hydroxymethyl age and the population dynamic DNA hydroxymethylation background can be calculated. Will be provided with18The tissue-specific dynamic DNA hydroxymethyl background determined by F-FDG PET data analysis is almost identical to the dynamic DNA methylation background determined directly by gene, and the difference in individual details is due to the fact that the dynamic DNA methylation background data determined by gene detection method is derived from Western people, while the method of the present invention determines the constitution of Chinese and study subjects (especially the total number and proportion of people in different age groups), the determination methodology, the adopted standard and the difference in individual subjects (such as smoking, heavy drinking, eating habits, treatment conditions and literature)Chemical differentiation) and the like. As shown in fig. 20 to 21, in the working module,18F-FDG PET can accurately analyze and determine the age of DNA hydroxymethyl in each age group, and the dynamic hydroxymethyl background formed by the age of DNA hydroxymethyl in each age group, thereby proving that the invention can accurately determine the static DNA hydroxymethyl background formed by the deviation of DNA hydroxymethyl in each organ tissue of an individual. The greater the number of target organ tissues measured, the more accurate the static DNA hydroxymethyl background. In the working module, based on the 18-25 years old DNA hydroxymethyl background as shown by curve E in FIG. 22, each organ tissue18The greater the deviation of the F-FDG uptake from curve E, the greater the deviation from the static DNA hydroxymethyl background, and the percentage of deviation was used to calculate the DNA hydroxymethyl background deviation for each target organ tissue, as compared to curve E. Finally, the static DNA hydroxymethyl background of each individual is sketched as shown in figure 23, and the static hydroxymethyl background of each individual is compared with the static hydroxymethyl background of the normal persons of the same age and the cancer patients, so as to judge the specific degree of deviation of the DNA hydroxymethyl background, as shown in figure 23, the left graph I line is the young DNA hydroxymethyl background, and the fetal DNA methylation background is directly measured relative to the right side. The left panel J shows the background of DNA methylation of various tissues of cancer patients, which is severely deviated from the positive rail and from the background of DNA methylation of right cancer cells compared with the background of youthfulness. The right line L, which is the degree of background deviation of the 55 year old control group DNA hydroxymethyl, is between normal and patient based, and the background deviation of DNA methylation of each tissue of a normal adult relative to the right line is between normal and cancer cells. The left dashed line, K, is the tissue-specific hydroxymethyl background bias for 1 example 55 year old subject.
Acquisition of a human body by means of a positron emission computed tomography scanner18F-FDG PET non-attenuation correction original data image; or the attenuation-corrected image data is converted to form a non-attenuation-corrected image.
Using ROI method or SUV value method in human body18The interested region of each target organ tissue is outlined on the F-FDG PET sectional image, and the system automatically forms the interested region18F-FDG total count, maximum count and average count/pixel, and extracting each target organ group by using average count/pixelWoven fabric18F-FDG count rate of each target organ tissue to be extracted18F-FDG count rate data is input into an organ tissue uptake rate calculation module, the computer automatically deducts background count, and then calculates the ratios of brain/cerebellum, white matter/cerebellum of brain, other organ tissues/lung and lung/main organs (liver, kidney, bone marrow and skeletal muscle) which are used as the ratio of each target organ tissue18F-FDG relative uptake and was automatically summarized in the database.
The tissue-specific DNA hydroxymethyl background primary parameters comprise dynamic DNA hydroxymethyl background primary parameters of each target organ tissue and static DNA hydroxymethyl background primary parameters of each target organ tissue;
the tissue-specific DNA hydroxymethyl background secondary parameters comprise a table chart for drawing various disease-related epigenotypes for chronic disease prevention and rehabilitation and calculation related parameters; analyzing and measuring biological clock, environmental stress, aging and health index of each target organ and tissue; and matching degree calculation for searching various intervention means by using the background parameters of DNA hydroxymethyl.
The method for measuring the first-level parameters of the dynamic DNA hydroxymethyl background of each target organ tissue comprises the following steps,
(S1) treating the target organ tissues18The F-FDG uptake rate is input into a working module, and the system automatically adjusts the F-FDG uptake rate according to the working curve18The F-FDG uptake rate is converted into the DNA hydroxymethyl age of each target organ tissue;
(S2) averaging the age of hydroxymethyl in DNA of brain, white matter of brain, lung, liver, kidney, bone marrow and skeletal muscle, and calculating the age of DNA methylation of each individual, i.e. the age of epigenetic clock;
(S3) subtracting the actual age from the hydroxymethyl age of the DNA of each target organ tissue, and automatically calculating the accelerated aging age of the DNA of each target organ tissue, wherein the accelerated aging age of the DNA of each target organ tissue is called as DANhm AA for short;
(S4) the age for accelerating aging of DNA of each person is automatically calculated by subtracting the actual age from the age for methylating DNA of each person.
The derivation method of the tissue-specific DNA hydroxymethyl background secondary parameter from the tissue-specific DNA hydroxymethyl background primary parameter comprises the following steps:
life expectancy ═ (age expected-age of DNA methylation) + actual age; as shown in figure 24, wherein the region F is a longevity region, and in the longevity region, the proportion of women is the highest, accounting for 26%; the proportion of cancer patients is very low, only 2.8%; the G area is a life shortening area, and the female proportion is at least 20.1%; the proportion of cancer patients accounts for 40.5% at most; FIG. 1 shows that a male is 55 years old, and DNA hydroxymethyl is accelerated to-3.2 years old, located in a longevity domain.
An age-accelerated DNA-methylol chart was drawn in which the location of the individual was marked to visually demonstrate life expectancy as shown in FIG. 24. The degree of deviation of the DNA hydroxymethylation background of each target organ tissue and a chart represent the static DNA hydroxymethylation background of each individual tissue, and the detected individual background is compared with a 25-year-old young state hydroxymethyl background, a peer hydroxymethyl background and a cancer patient hydroxymethyl background. The background bias of the assay is consistent with the direct determination of DNA methylation bias.
The unhealthy index reference value is the average value of brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA of the age group of the cancer patient and then multiplied by a correlation coefficient 1;
the health index reference value is the average value of normal human brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA, and then multiplied by the corresponding correlation coefficient value of the cancer patient;
the sub-health index of the subject is determined by averaging the brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA, and skeletal muscle DANhm AA of the age group of the cancer patient and multiplying the average by the corresponding correlation coefficient value of the cancer patient.
Determination and calculation of static DNA hydroxymethyl background primary parameters of each target organ tissue:
DNAhm rejuvenation background value of normal target organ tissues in the age group of 18-25 years18(ii) the average F-FDG uptake rate, representing the younger DNA hydroxymethyl level of the target organ tissue;
DNAhm deviation from the threshold values for each target organ tissue of all cancer patients18Average F-FDG uptake, representing severe deviation from the level of DNA hydroxymethyl in the target organ tissue;
DNAhm deviating from the expected value refers to the tissues of each target organ of normal people of the same age group18Average F-FDG uptake rate, representing the average deviation level of DNA hydroxymethyl of the target organ tissues;
DNAhm deviation from the determined values, for each target organ tissue of the subject18(ii) an F-FDG uptake rate representing DNA hydroxymethyl bias levels of a target organ tissue of the subject;
the deviation threshold of hydroxymethyl background refers to the average value of the deviation of hydroxymethyl background of DNA of brain, white matter of brain, heart, lung, liver, kidney, skeletal muscle and bone marrow of all cancer patients;
the deviation of the hydroxymethyl background from an expected value refers to the average value of the deviation of the hydroxymethyl background of the DNA of the brain, the white matter of the brain, the heart, the lung, the liver, the kidney, the skeletal muscle and the bone marrow of normal people in the same age group;
a hydroxymethyl background deviation index, which refers to a measure of the deviation in hydroxymethyl background of the subject's brain, white matter of brain, heart, lung, liver, kidney, skeletal muscle and bone marrow DNA;
a hydroxymethyl background deviation measurement, which refers to the mean of the hydroxymethyl background deviation indices of the subject's brain, white matter of brain, heart, lung, liver, kidney, skeletal muscle and bone marrow;
the degree of deviation of hydroxymethylation means the percentage of deviation of hydroxymethylation in each target organ tissue compared with the background value of the younger age group between 18 years and 25 years, and the larger the percentage, the more serious the deviation of background.
Calculating the secondary parameters of the tissue-specific DNA hydroxymethyl background:
the biological clock coordination index is used for measuring the coordination of the white matter of the brain of the mother clock of the biological clock and the DNA hydroxymethyl background of the clock (brain, liver, kidney, skeletal muscle and adrenal gland) of peripheral tissues, calculating the difference value of the hydroxymethyl level of the white matter of the brain and the hydroxymethyl level of the brain, liver, kidney, skeletal muscle and adrenal gland, and the size of the standard deviation among the difference values represents the harmony of the biological clock, namely the larger the standard deviation is, the better the coordination of the biological clock is; conversely, the smaller the standard deviation, the worse the biological clock coordination;
cancer risk index and risk score, characteristic hydroxymethyl backgrounds of cancer patients determined according to the method of the present invention, as shown in fig. 6, the major target organs with severe deviations of hydroxymethyl are brain, white brain matter, liver, kidney and skeletal muscle, respectively, and brain (weight 1) ═ white brain matter (weight 1) is ranked according to the degree of deviation>Liver (weight 0.9) ═ kidney (weight 0.9)>Skeletal muscle (weight 0.7). Thus, cancer risk index is brain weight/brain18F-FDG uptake + white brain protein weight/white brain protein18F-FDG uptake rate + liver weight 3/liver18F-FDG uptake + Kidney weight 3/Kidney18F-FDG uptake + skeletal muscle weight/skeletal muscle18F-FDG uptake. A risk score of 100% (subject cancer risk index/cancer patient cancer risk index), greater than 85% (85 points) being high risk for cancer;
risk index and risk score of senile nervous system diseases, the characteristic hydroxymethyl background of senile nervous system diseases measured according to the method of the present invention, as shown in fig. 6, the major target organs with severe deviation of hydroxymethyl, and the liver (weight 0.8) ═ kidney (weight 0.8) ═ bone marrow (weight 0.8) are sorted according to the deviation degree>Brain (weight 0.7) ═ white brain matter (weight 0.7)>Skeletal muscle (weight 0.6). Thus, the geriatric neurological risk index is the brain weight/brain18F-FDG uptake + white brain protein weight/white brain protein18F-FDG uptake rate + liver weight 3/liver18F-FDG uptake + Kidney weight 3/Kidney18F-FDG uptake + skeletal muscle weight/skeletal muscle18F-FDG uptake. (ii) a risk score of (subject risk index for geriatric neurological disease/risk index for geriatric neurological disease patient) × 100%, greater than 87% (87 points) is a high risk for geriatric neurological disease;
diabetes risk index and risk score, the background of hydroxymethyl characteristic of diabetes determined according to the method of the present patent, FIG. FIG6, the major target organs with severe deviations of hydroxymethyl, according to the deviationDegree ordering skeletal muscle (weight 0.9)>Kidney (weight 0.8)>Liver (weight 0.7) ═ bone marrow (weight 0.7)>Brain (weight 0.6) ═ white matter (weight 0.6)>Skeletal muscle (weight 0.6), therefore, diabetes risk index ═ brain weight/brain18F-FDG uptake + white brain protein weight/white brain protein18F-FDG uptake rate + liver weight 3/liver18F-FDG uptake + Kidney weight 3/Kidney18F-FDG uptake + skeletal muscle weight/skeletal muscle18F-FDG uptake, risk score (subject diabetes risk index/diabetic risk index) 100%, greater than 85% (85 points) is diabetes risk;
the environmental stress index reflects the functional state of the neuroimmune system, and constructs unique background characteristics of the hydroxymethyl in the brain, adrenal gland, spleen and digestive tract (colon). Thus, the environmental stress index (adrenal gland)18F-FDG uptake + spleen18F-FDG uptake + Colon18F-FDG uptake)/brain18F-FDG uptake, environmental stress index healthy, cut-off, control and measured values represent environmental stress index values for the age group of 18-25 years, cancer patient group, cohort and subject, respectively;
the low level inflammation tandem index is a very important aging index and disease risk index, and has the epigenetic change characteristics of intestinal dysbacteriosis and tandem connection of skeletal muscle, liver and brain. Thus, a low level of cascade index of inflammation is colon18F-FDG uptake/(skeletal muscle)18F-FDG uptake + liver18F-FDG uptake + brain18F-FDG uptake rate). Low level inflammatory cascade index healthy, cut-off, control and measured values represent environmental stress index values for the age group of 18-25 years, cancer patient group, cohort and subject, respectively;
calculating the matching degree of the tissue-specific DNA hydroxymethyl background secondary parameters:
according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the action of a certain medicament is searched, and the personalized guidance of clinical medication is as follows: the degree of matching is the degree of correlation between the degree of efficacy of the drug on each target tissue and the degree of background deviation of DNA in each target organ. The positive correlation coefficient is between 0 and 1, and the larger the correlation coefficient is, the more toxic the medicament is to a subject is, and the larger the side effect is; the negative correlation coefficient is between 0 and-1, the greater the correlation coefficient, the less toxic the drug to the subject and the less side effects.
According to the static background deviation of individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background and a certain food active ingredient is searched, and personalized nutrition is guided: the degree of matching is the degree of correlation between the degree of background of DNA methylation in each target tissue improved by the nutritionally active substance and the degree of background deviation from DNA hydroxymethyl in each target organ. The positive correlation coefficient is between 0 and 1, and the larger the correlation coefficient is, the better the effect of the nutrition health care product on a subject is; the negative correlation coefficient is between 0 and-1, the greater the correlation coefficient, the less effective the nutraceutical is on the subject.
According to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background and the exercise fitness and the benefit degree of the exercise on the health are searched: the degree of matching is that exercise can improve the degree of correlation between the degree of background of DNA methylation of each target tissue and the degree of deviation of background of DNA hydroxymethyl of each target organ. The positive correlation coefficient is between 0 and 1, the larger the correlation coefficient, the more beneficial the exercise fitness is to the subject.
According to the deviation of the static background of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background and the human body biological clock is searched, and the bad living habits are corrected in a personalized way: the degree of matching is the degree of correlation between the degree of DNA methylation background of each target tissue and the degree of DNA hydroxymethyl background deviation of each target organ influenced by bad lifestyle. The positive correlation coefficient is between 0 and 1, and the larger the correlation coefficient is, the more harmful the bad life habits are to the subject.
According to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the thermal card limiting effect is searched for, and personalized anti-aging is carried out: the matching degree, namely the thermal card limitation, improves the degree of correlation between the degree of DNA methylation background of each target tissue and the degree of deviation of DNA hydroxymethyl background of each target organ. The positive correlation coefficient is between 0 and 1, and the greater the correlation coefficient, the greater the benefit of the thermal card limit to the subject.
According to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background and the methylation background of the serious chronic disease is searched, and personalized disease prevention is carried out: the degree of match is the degree of correlation between the background of DNA methylation for each disease and the degree of deviation from the background of DNA hydroxymethyl for each target organ. The positive correlation coefficient is between 0 and 1, and the larger the correlation coefficient, the greater the risk of disease.
According to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background with the situations and other situations is searched, and the calculation method is the same and is used for disease auxiliary treatment, disease rehabilitation, prenatal and postnatal care and health care.
Use of18The background method for analyzing and determining tissue-specific DNA hydroxymethyl by F-FDG PET molecular image data is applied to the following fields:
(H1) evaluating health level and predicting life according to dynamic hydroxymethyl background;
(H2) predicting and preventing major chronic diseases according to the characteristic hydroxymethyl background of the major chronic diseases;
(H3) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the drug action is searched, and the clinical medication is guided in a personalized way;
(H4) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the food active ingredients is searched, and personalized nutrition is guided;
(H5) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the exercise fitness and the benefit degree of the exercise on the health are searched;
(H6) according to the deviation of the static background of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the human body biological clock is searched, and the bad living habits are corrected in a personalized manner;
(H7) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the chronic low-level inflammatory reaction and the matching degree of the thermal card limiting effect are searched for, and personalized anti-aging is carried out;
(H8) according to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background with the situations and other situations is searched for the disease auxiliary treatment, the disease rehabilitation, the prenatal and postnatal care and the health care.
The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.
Claims (5)
1. Human body18A method for analyzing the background of DNA hydroxymethyl in tissue by F-FDG PET data, which is characterized by comprising the following steps:
(1) obtaining adults18F-FDG whole body tomograms;
(2) extracting 18F-FDG data of each target tissue by ROI method or SUV value method, calculating glucose uptake rate, and establishing correspondence of sex-based age18A database of F-FDG uptake rates;
(3) correcting a DNA telomere linear shortening curve according to the background of each target organ tissue database of the normal adult and the fitting of the background, and establishing a working module for analyzing and determining the background of DNA hydroxymethyl;
(4) determining a tissue-specific DNA hydroxymethyl background primary parameter and a tissue-specific DNA hydroxymethyl background secondary parameter;
the tissue-specific DNA hydroxymethyl background primary parameters comprise dynamic DNA hydroxymethyl background primary parameters of each target organ tissue and static DNA hydroxymethyl background primary parameters of each target organ tissue;
the tissue-specific DNA hydroxymethyl background secondary parameters comprise a table chart for drawing various disease-related epigenotypes for chronic disease prevention and rehabilitation and calculation related parameters; analyzing and measuring biological clock, environmental stress, aging and health index of each target organ and tissue; and using the background parameters of DNA hydroxymethyl to search the matching degree calculation of various intervention means;
the method for measuring the first-level parameters of the dynamic DNA hydroxymethyl background of each target organ tissue comprises the following steps,
(S1) treating the target organ tissues18The F-FDG uptake rate is input into a working module, and the system automatically adjusts the F-FDG uptake rate according to a working curve18The F-FDG uptake rate is converted into the DNA hydroxymethyl age of each target organ tissue;
(S2) averaging the age of hydroxymethyl in DNA of brain, white matter of brain, lung, liver, kidney, bone marrow and skeletal muscle, and calculating the age of DNA methylation of each individual, i.e. the age of epigenetic clock;
(S3) subtracting the actual age from the hydroxymethyl age of the DNA of each target organ tissue, and automatically calculating the accelerated aging age of the DNA of each target organ tissue, wherein the accelerated aging age of the DNA of each target organ tissue is called as DANhm AA for short;
(S4) automatically calculating the age-accelerated DNA age of each person by subtracting the actual age from the age of DNA methylation of each person;
the derivation method of the tissue-specific DNA hydroxymethyl background secondary parameter from the tissue-specific DNA hydroxymethyl background primary parameter comprises the following steps:
life expectancy (expected age-age of DNA methylation) + actual age.
2. A human body as claimed in claim 118A method for analyzing the background of DNA hydroxymethyl in tissues by F-FDG PET data is characterized in that: acquisition of a human body by means of a positron emission computed tomography scanner18F-FDG PET non-attenuation correction original data image; or the attenuation-corrected image data is converted to form a non-attenuation-corrected image.
3. A human body as claimed in claim 118A method for analyzing the background of DNA hydroxymethyl in tissues by F-FDG PET data is characterized in that: using ROI method or SUV value method in human body18The interested region of each target organ tissue is outlined on the F-FDG PET sectional image, and the system automatically forms the interested region18F-FDG total count, maximum count and average count/pixel, and extracting the tissue of each target organ by using the average count/pixel18F-FDG count rate of each target organ tissue to be extracted18F-FDG count rate data is input into an organ tissue uptake rate calculation module, the computer automatically deducts background count, and then calculates the ratios of brain/cerebellum, white matter/cerebellum of brain, other organ tissues/lung, lung/liver, kidney, bone marrow and skeletal muscle, and the ratios are used as the ratios of various target organ tissues18F-FDG relative uptake and was automatically summarized in the database.
4. A human body as claimed in claim 118A method for analyzing the background of DNA hydroxymethyl in tissues by F-FDG PET data is characterized in that: the tissue-specific DNA hydroxymethyl background secondary parameter is derived from the tissue-specific DNA hydroxymethyl background primary parameter by the method comprising the following steps,
life expectancy ═ (age expected-age of DNA methylation) + actual age;
the unhealthy index reference value is the average value of brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA of the age group of the cancer patient and then multiplied by a correlation coefficient 1;
the health index reference value is the average value of normal human brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA and skeletal muscle DANhm AA, and then multiplied by the corresponding correlation coefficient value of the cancer patient;
the sub-health index of the subject is determined by averaging the brain DANhm AA, brain white matter DANhm AA, lung DANhm AA, liver DANhm AA, kidney DANhm AA, bone marrow DANhm AA, and skeletal muscle DANhm AA of the age group of the cancer patient and multiplying the average by the corresponding correlation coefficient value of the cancer patient.
5. A human body as claimed in claim 118The application of the method for analyzing the tissue DNA hydroxymethyl background by F-FDG PET data is characterized by being applied to the following fields:
(H1) evaluating health level and predicting life according to dynamic hydroxymethyl background;
(H2) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the food active ingredients is searched, and personalized nutrition is guided;
(H3) according to the static background deviation of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the exercise fitness and the benefit degree of the exercise on the health are searched;
(H4) according to the deviation of the static background of the individual tissue specificity DNA hydroxymethyl, the matching degree of the methylation background and the human body biological clock is searched, and the bad living habits are corrected in a personalized manner;
(H5) according to the static background deviation of the individual tissue-specific DNA hydroxymethyl, the matching degree of the methylation background and the chronic low-level inflammatory reaction and the matching degree of the thermal card limiting effect are searched, and personalized anti-aging is carried out.
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