A metabolic-immune based crohn's disease prediction system

Abstract

The application relates to the technical field of medical data processing, in particular to a Crohn disease prediction system based on metabolism-immunity, which comprises a collection module, a peripheral blood and a colon mucosa biopsy sample of a subject are collected to obtain data; a prediction module, Treg cell function index is calculated according to the data, fatty acid oxidation pathway activation index is calculated; a Crohn risk index is calculated and a result is output; the application takes an ALA-CPT1A / CD36-FAO-Treg cell function regulation axis as a core, quantitatively couples alpha-linolenic acid concentration, expression of a core molecule of an FAO pathway, a Treg cell function comprehensive index and a clinical correction factor, and sequentially constructs: a Treg cell function comprehensive index reflecting an immune core state; an FAO pathway synergistic activation index reflecting a regulation effect of metabolism on immunity; and prediction is realized in combination with the Treg cell function comprehensive index, the FAO index and clinical correction.

Description

Technical Field

[0001] This invention relates to the field of medical data processing technology, specifically to a Crohn's disease prediction system based on metabolism and immunity. Background Technology

[0002] Currently, most predictive systems for Crohn's disease rely on preliminary assessments based solely on patients' clinical symptoms and routine blood test results. These indicators often only show significant abnormalities after the disease has progressed to a certain stage, resulting in insufficient sensitivity and specificity for early prediction.

[0003] Therefore, this invention proposes a metabolism-immunity-based Crohn's disease prediction system that can couple the metabolic and immune systems to predict Crohn's disease. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a metabolism-immunity-based Crohn's disease prediction system that can couple the metabolic system and the immune system to predict Crohn's disease.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows: A metabolic-immune-based Crohn's disease prediction system includes: The data collection module collects peripheral blood and colonic mucosal biopsy samples from the subjects to obtain the relative expression level of Foxp3 protein. IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level , peripheral blood -Linolenic acid concentration value Concentration of short-chain fatty acids produced by gut microbiota Intestinal barrier function coefficient ; Prediction module Calculate Treg cell function index , = + + ; Calculate the activation index of fatty acid oxidation pathway , = λ ; Calculate the Crohn's Risk Index , = ; in, - These are the weighting coefficients; These are the molecular weighting coefficients for the fatty acid oxidation pathway. Peripheral blood of healthy individuals - Reference value for linolenic acid concentration; λ is... -Linolenic acid dosage correction factor; when When ∈ (0, 0.8 μg / mL), λ = 1.2; when When ∈ (0.8, 1.5) μg / mL, λ = 1.0; when When the concentration is ≥1.5 μg / mL, λ = 0.5; This serves as the risk benchmark coefficient. It is a metabolic-immune synergistic system; For age correction factor, The genetic susceptibility coefficient for the CD family; according to Output results.

[0006] Preferably, the relative expression level of Foxp3 protein IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level SCFA concentration value of gut microbiota Intestinal barrier function coefficient After standardization, their respective value ranges are as follows: This yields dimensionless quantitative values.

[0007] Preferably, =1, and .

[0008] Preferably, according to The output further includes: 0 < ≤1.0 indicates that the subject has a good metabolic-immune coordination status, normal Treg cell function, sufficient activation of the fatty acid oxidation pathway, and a low risk of developing CD; 1.0 < <2.0 indicates an abnormal metabolic-immune synergistic state in the subject, insufficient activation of the fatty acid oxidation pathway or inappropriate ALA dosage, and the possibility of prodromal CD lesions, which is of medium risk and requires regular follow-up. ≥2.0 indicates a severe imbalance in the metabolic-immune synergistic axis, a significant decrease in Treg cell function, insufficient activation of the fatty acid oxidation pathway, and an extremely high risk of developing CD, requiring early intervention.

[0009] Preferably, the intestinal barrier function coefficient The values ​​were standardized based on Occludin protein expression levels, with values ​​ranging from [value range missing]. This yields dimensionless quantitative values.

[0010] Preferably, when the subject is under 30 years old, =0.8; when the subject's age is 30 50 years old =1.0; when the subject is older than 50 years, =0.9 Preferably, when a subject's first-degree relative has Crohn's disease, then =1.5, if not =1.0.

[0011] Preferably, The setting was 0.45 μg / mL.

[0012] Preferably, The value is 3.

[0013] The beneficial effects of this invention are as follows: By using the ALA-CPT1A / CD36-FAO-Treg cell function regulation axis as the core, it quantitatively couples α-linolenic acid (ALA) concentration, the expression levels of core FAO pathway molecules (CPT1A, CD36), Treg cell function comprehensive indicators, and clinical correction factors. This is achieved by sequentially constructing: a Treg cell function comprehensive index reflecting the core state of immunity; a fatty acid oxidation metabolism FAO pathway synergistic activation index reflecting the regulatory effect of metabolism on immunity; and a CD disease incidence risk prediction index, which, combined with the Treg cell function comprehensive index, FAO index, and clinical correction, achieves the final prediction. Furthermore, by introducing ALA (… The dose-dependent correction coefficient λ of alpha-linolenic acid (ALA) accurately reflects the bidirectional effect of ALA on CD, solving the problem that existing technologies do not consider the dose-effect of metabolites. By calculating the Treg cell function index, the phenotypic markers and functional effectors of Treg cells are quantitatively coupled to comprehensively reflect the immunosuppressive function of Treg cells, solving the problem that existing technologies only detect a single Treg indicator. The formula results provide a basis for the subsequent calculation of the FAO pathway activation index, because the core role of the FAO pathway is to maintain the function of Treg cells, and there is a direct causal regulatory relationship between the two. The fatty acid oxidation pathway index reflects the synergistic effect of the catalytic molecule (CPT1A) and transport molecule (CD36) of the FAO pathway through a product term, namely, the metabolic-immune synergistic effect. The short-chain fatty acids produced by the gut microbiota can promote Treg differentiation through the GPR43 signaling axis, enhancing the efficacy of ALA; that is, the gut barrier-microbiota synergistic correction term, reflecting the protective effect of gut barrier function and SCFA on CD pathogenesis. By correcting for multiple dimensions of clinical environmental factors such as age, genetics, gut barrier, and gut microbiota, a quantitative coupling of four dimensions of metabolism (main), immunity (main), clinical (impact), and microbiota (impact) is achieved, improving the accuracy of prediction. Attached Figure Description

[0014] Figure 1 This is a flowchart illustrating a Crohn's disease prediction system based on metabolism and immunity, as described in a specific embodiment of the present invention. Detailed Implementation

[0015] To explain in detail the technical content, objectives, and effects of the present invention, the following description is provided in conjunction with the embodiments and accompanying drawings.

[0016] Please refer to Figure 1 A metabolic-immune-based Crohn's disease prediction system includes: The data collection module collects peripheral blood and colonic mucosal biopsy samples from the subjects to obtain the relative expression level of Foxp3 protein. IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level , peripheral blood -Linolenic acid concentration value Concentration of short-chain fatty acids produced by gut microbiota Intestinal barrier function coefficient ; Prediction module Calculate Treg cell function index , = + + ; Calculate the activation index of fatty acid oxidation pathway , = λ ; Calculate the Crohn's Risk Index , = ; in, - These are the weighting coefficients; These are the molecular weighting coefficients for the fatty acid oxidation pathway. Peripheral blood of healthy individuals - Reference value for linolenic acid concentration; λ is... -Linolenic acid dosage correction factor; when When ∈ (0, 0.8 μg / mL), λ = 1.2; when When ∈ (0.8, 1.5) μg / mL, λ = 1.0; when When the concentration is ≥1.5 μg / mL, λ = 0.5; This serves as the risk benchmark coefficient. It is a metabolic-immune synergistic system; For age correction factor, The genetic susceptibility coefficient for the CD family; according to Output results.

[0017] As described above, by focusing on the ALA-CPT1A / CD36-FAO-Treg cell function regulation axis, and quantitatively coupling α-linolenic acid (ALA) concentration, expression levels of core FAO pathway molecules (CPT1A, CD36), Treg cell function comprehensive indicators, and clinical correction factors, the following were constructed sequentially: a Treg cell function comprehensive index reflecting the core immune status; a fatty acid oxidation metabolism FAO pathway co-activation index reflecting the regulatory effect of metabolism on immunity; and a CD disease incidence risk prediction index, which, combined with the Treg cell function comprehensive index, FAO index, and clinical correction, achieves the final prediction; and by introducing ALA ( The dose-dependent correction coefficient λ of alpha-linolenic acid (ALA) accurately reflects the bidirectional effect of ALA on CD, solving the problem that existing technologies do not consider the dose-effect of metabolites. By calculating the Treg cell function index, the phenotypic markers and functional effectors of Treg cells are quantitatively coupled to comprehensively reflect the immunosuppressive function of Treg cells, solving the problem that existing technologies only detect a single Treg indicator. The formula results provide a basis for the subsequent calculation of the FAO pathway activation index, because the core role of the FAO pathway is to maintain the function of Treg cells, and there is a direct causal regulatory relationship between the two. The fatty acid oxidation pathway index reflects the synergistic effect of the catalytic molecule (CPT1A) and transport molecule (CD36) of the FAO pathway through a product term, namely, the metabolic-immune synergistic effect. The short-chain fatty acids produced by the gut microbiota can promote Treg differentiation through the GPR43 signaling axis, enhancing the efficacy of ALA; that is, the gut barrier-microbiota synergistic correction term, reflecting the protective effect of gut barrier function and SCFA on CD pathogenesis. By correcting for multiple dimensions of clinical environmental factors such as age, genetics, gut barrier, and gut microbiota, a quantitative coupling of four dimensions of metabolism (main), immunity (main), clinical (impact), and microbiota (impact) is achieved, improving the accuracy of prediction.

[0018] Furthermore, the relative expression level of Foxp3 protein IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level SCFA concentration value of gut microbiota Intestinal barrier function coefficient After standardization, their respective value ranges are as follows: This yields dimensionless quantitative values.

[0019] As can be seen from the above description, standardization facilitates calculations and establishes a unified standard.

[0020] Furthermore, =1, and .

[0021] As can be seen from the above description, The highest weight is due to Foxp3 being the core of the Treg function.

[0022] Furthermore, according to The output further includes: 0 < ≤1.0 indicates that the subject has a good metabolic-immune coordination status, normal Treg cell function, sufficient activation of the fatty acid oxidation pathway, and a low risk of developing CD; 1.0 < <2.0 indicates an abnormal metabolic-immune synergistic state in the subject, insufficient activation of the fatty acid oxidation pathway or inappropriate ALA dosage, and the possibility of prodromal CD lesions, which is of medium risk and requires regular follow-up. ≥2.0 indicates a severe imbalance in the metabolic-immune synergistic axis, a significant decrease in Treg cell function, insufficient activation of the fatty acid oxidation pathway, and an extremely high risk of developing CD, requiring early intervention.

[0023] Furthermore, the intestinal barrier function coefficient The values ​​were standardized based on Occludin protein expression levels, with values ​​ranging from [value range missing]. This yields dimensionless quantitative values.

[0024] As described above, ALA can also repair intestinal barrier function and reduce chronic inflammation caused by bacterial translocation by upregulating tight junction proteins (Occludin, ZO-1). Therefore, the intestinal barrier function coefficient... This is how it's set up.

[0025] Furthermore, when the subjects were under 30 years old, =0.8; when the subject's age is 30 50 years old =1.0, when the subject is older than 50 years old. =0.9 As can be seen from the above description, the peak incidence of CD is between 30 and 50 years old, during which the risk is the highest. The risk decreases as the age deviates from this range. Furthermore, when a subject's first-degree relative has Crohn's disease, then... =1.5, if not =1.0.

[0026] Furthermore, The setting was 0.45 μg / mL.

[0027] Furthermore, The value is 3.

[0028] Example 1 A metabolic-immune-based Crohn's disease prediction system includes: The data collection module collects peripheral blood and colonic mucosal biopsy samples from the subjects to obtain the relative expression level of Foxp3 protein. IL-10 secretion concentration value TGF-β secretion concentration value , Relative expression level of CPT1A protein , Relative expression level of CD36 protein , Peripheral blood -linolenic acid concentration value , Concentration value of short-chain fatty acids produced by intestinal flora , Intestinal barrier function coefficient ; Except for , all other elements are standardized dimensionless values (forming a unified standard to facilitate subsequent value calculation), with a range of 0<x≤1 (x here refers to the meaning of each element, not specifically limited to a certain one).

[0029] a prediction module, calculates the Treg cell function index , = + + (Equation 1) : Treg cell function index, a larger value indicates stronger immunosuppressive function of Treg cells and more significant protective effect on CD; : Standardized value of the relative protein expression level of Foxp3, a signature molecule of Treg cells, which is the core marker of Treg cell function (stable expression of Foxp3 is the key to the maintenance of Treg function); : Standardized value of the concentration of the inhibitory cytokine IL-10 secreted by Treg cells; : Standardized value of the concentration of the inhibitory cytokine TGF-β secreted by Treg cells; : Indicator weight coefficient, which can be obtained by fitting based on the core role of the molecule and clinical big data, and for the convenience of understanding, the values are set as =0.5, =0.3, =0.2 (Foxp3 is the core of Treg function and has the highest weight), and =1.

[0030] calculates the fatty acid oxidation (FAO) pathway activation index , = λ (Equation 2) The higher the value, the higher the activation level of the FAO pathway, the stronger the synergistic effect with Treg cell function, and the more significant the protective effect against CD4. : Normalized relative expression level of CPT1A protein, the core catalytic molecule of the FAO pathway (which mediates the entry of acyl-CoA into mitochondria for β-oxidation); : Normalized relative expression level of CD36 protein, a fatty acid transport molecule in the FAO pathway (which provides substrate for FAO and interacts with CPT1A). The synergistic effect of CPT1A and CD36 reflects their coupling effect in the FAO pathway (the interaction between the two can be detected by immunoprecipitation, which is the core of FAO pathway activation). Peripheral blood of subjects -Linolenic acid concentration value; Peripheral blood from healthy individuals - Reference value for linolenic acid concentration, Reflects the ratio of ALA concentration in the subjects to that in healthy individuals; The value was set to 0.45 μg / mL (based on the average value of the sums of data from healthy individuals; this value can be adjusted based on different statistical or calculation methods).

[0031] The weighting coefficient between FAO pathway molecules and ALA, with a value of α=0.6 (for illustrative purposes only, no specific value is limited), indicates that the role of the core FAO pathway molecule (CPT1A / CD36) is more significant. (1) α) = 0.4 represents the percentage of ALA's effect; λ: ALA dose-dependent correction factor, the core point, dose-response design based on ALA, when This serves as the risk benchmark coefficient. The comprehensive Treg cell function index calculated by Formula 1 reflects the causal regulatory relationship between the FAO pathway and Treg cell function (activation of the FAO pathway is the metabolic basis for maintaining Treg function, therefore...). (Introduced as a control coefficient).

[0032] Calculate the Crohn's Risk Index , = (Formula 3) : A larger value indicates a higher risk of developing CD in the subject, and a smaller value indicates a lower risk of developing the disease; : The risk reference coefficient is a constant that can be obtained by fitting based on clinical big data, and its value =3.0 (for illustrative purposes only, and does not limit the specific value); : The weight coefficient of the metabolism-immunity synergistic indicator, with a value of β=0.7, represents the synergistic effect between the FAO pathway and Treg ( ) is the core regulatory factor for the onset of CD, (1 β)=0.3 is the proportion of the basic function of Treg cells ( ), which is the core mechanism by which metabolic reprogramming regulates immune imbalance; : Age adjustment coefficient, value taking rule: <30 years old =0.8, 30 50 years old =1.0, >50 years old =0.9 (the peak incidence of CD is 30-50 years old, and the risk decreases when the age deviates from this interval); : CD familial genetic susceptibility coefficient, no family history =1.0, having a family history of first-degree relatives (referring to the individual's parents, children, and full siblings) =1.5 (reflecting the modifying effect of genetic factors); : Intestinal barrier function coefficient, which is obtained by standardizing the expression level of Occludin protein. A larger value indicates stronger intestinal barrier function, with a value of 0< ≤1 (ALA can up-regulate Occludin and repair the intestinal barrier); : Standardized value of the concentration of short-chain fatty acids (SCFA) produced by intestinal flora. A larger value indicates a higher SCFA content, with a value of 0<CSCFA≤1 (SCFA can promote Treg differentiation through the GPR43 signaling axis and enhance the therapeutic effect of ALA); : Intestinal barrier-flora synergistic correction term, which reflects the protective effect of intestinal barrier function and SCFA on the onset of CD (the smaller the value, the stronger the protective effect and the lower the risk).

[0033] According to output the result.

[0034] Low risk: 0< ≤1.0 indicates that the subject has a good metabolic-immune coordination status, normal Treg cell function, sufficient activation of the fatty acid oxidation pathway, and a low risk of developing CD; Medium risk: 1.0 < <2.0 indicates an abnormal metabolic-immune synergistic state in the subject, insufficient activation of the fatty acid oxidation pathway or inappropriate ALA dosage, and the possibility of CD prodromal lesions, which is of medium risk and requires regular follow-up; High risk: ≥2.0 indicates a severe imbalance in the metabolic-immune synergistic axis, a significant decrease in Treg cell function, insufficient activation of the fatty acid oxidation pathway, and an extremely high risk of developing CD, requiring early intervention.

[0035] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent modifications made based on the content of the present invention specification and drawings, or direct or indirect applications in related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A Crohn's disease prediction system based on metabolism and immunity, characterized in that, include: The data collection module collects peripheral blood and colonic mucosal biopsy samples from the subjects to obtain the relative expression level of Foxp3 protein. IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level , peripheral blood -Linolenic acid concentration value Concentration of short-chain fatty acids produced by gut microbiota Intestinal barrier function coefficient ; The prediction module calculates the Treg cell function index. , = + + ; Calculate the activation index of fatty acid oxidation pathway , = λ ; Calculate the Crohn's Risk Index , = ; in, , , These are the weighting coefficients; These are the molecular weighting coefficients for the fatty acid oxidation pathway. Peripheral blood of healthy individuals - Reference value for linolenic acid concentration; λ is... -Linolenic acid dosage correction factor; when When ∈ (0, 0.8] μg / mL, λ = 1.2; when When ∈ (0.8, 1.5) μg / mL, λ = 1.0; when When the concentration is ≥1.5 μg / mL, λ = 0.5; This serves as the risk benchmark coefficient. These are the weighting coefficients; This is the age correction factor. The genetic susceptibility coefficient for the CD family; according to Output results.

2. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, Relative expression level of Foxp3 protein IL-10 secretion concentration value TGF-β secretion concentration value Relative expression level of CPT1A protein CD36 protein relative expression level SCFA concentration value of gut microbiota Intestinal barrier function coefficient After standardization, their respective value ranges are as follows: This yields dimensionless quantitative values.

3. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, =1, and .

4. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, according to The output further includes: 0 < ≤1.0 indicates that the subject has a good metabolic-immune coordination status, normal Treg cell function, sufficient activation of the fatty acid oxidation pathway, and a low risk of developing CD; 1.0 < <2.0 indicates an abnormal metabolic-immune synergistic state in the subject, insufficient activation of the fatty acid oxidation pathway or inappropriate ALA dosage, and the possibility of CD prodromal lesions, which is of medium risk and requires regular follow-up; ≥2.0 indicates a severe imbalance in the metabolic-immune synergistic axis, a significant decrease in Treg cell function, insufficient activation of the fatty acid oxidation pathway, and an extremely high risk of developing CD, requiring early intervention.

5. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, Intestinal barrier function coefficient The values ​​were standardized based on Occludin protein expression levels, with values ​​ranging from [value range missing]. This yields dimensionless quantitative values.

6. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, When the subjects were under 30 years old =0.8; when the subject's age is 30 50 years old =1.0; when the subject is older than 50 years, =0.

9.

7. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, When a subject's first-degree relative has Crohn's disease, =1.5, if not =1.

0.

8. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, The setting was 0.45 μg / mL.

9. The Crohn's disease prediction system based on metabolism and immunity according to claim 1, characterized in that, The value is 3.

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