Application of hnrnpa2b1 gene expression level detection material in detection of postpartum depression and detection system
By using HNRNPA2B1 gene expression level detectors and their combinations, the challenge of early diagnosis of postpartum depression has been solved, achieving high-precision detection of postpartum depression and ensuring the health of mothers and infants.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-04-02
- Publication Date
- 2026-03-24
AI Technical Summary
Current technology lacks effective means and quantitative standards for diagnosing postpartum depression, leading to an inability to diagnose it early and consequently causing serious adverse consequences for both mothers and infants.
Using HNRNPA2B1 gene expression level detectors and their combinations, a postpartum depression detection product and system were developed through non-invasive quantitative detection. The system includes a gene expression level acquisition module and a judgment module, and uses the expression levels of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 genes as classifiers for early diagnosis.
It enables early and accurate diagnosis of postpartum depression, with an area under the ROC curve of over 0.75, reaching a maximum of 0.902, making it suitable as a clinical early diagnostic reagent and avoiding the adverse effects of postpartum depression.
Smart Images
Figure CN115261460B_ABST
Abstract
Description
[0001] The application is a divisional application of the invention patent with the title of a postpartum depression detection reagent, system and application, application number 202110360705.4, and the application date of April 2, 2021. TECHNICAL FIELD
[0002] The application belongs to the field of biochemical detection, and particularly relates to application of HNRNPA2B1 gene expression level detection substance in postpartum depression detection and a detection system. BACKGROUND
[0003] Postpartum depression (PPD) affects 10-15% of postpartum women and is one of the most prominent risk factors for mood disorders in postpartum women. Its clinical symptoms usually occur within two weeks after delivery, and patients have persistent and severe emotions, including negative emotions (such as sadness, anxiety, worthlessness or despair), low energy and social isolation tendency. Postpartum depression can have short-term and long-term negative effects on the development, cognition, emotion and behavior of newborns. Studies have shown that maternal depression is a risk factor for premature infants and low birth weight infants, infant malnutrition and developmental delay, and it has gradually become a major public health problem.
[0004] Postpartum depression is the result of the combined effects of multiple factors. Recent studies have proposed hypotheses about the physiological and pathological mechanisms of postpartum depression, including abnormal changes in hormones, neurotransmitters and inflammatory factors, as well as genetics, social environment, psychological state, infant delivery method, etc. However, there is no conclusive evidence to support any of the above conclusions, and the physiological and pathological mechanisms of postpartum depression remain largely unclear. Due to the complexity of the pathogenesis of postpartum depression, there is currently a lack of effective means and quantitative standards to diagnose postpartum depression, resulting in the fact that postpartum depression can often only be judged after the fact, leading to serious adverse consequences for infants and mothers.
[0005] Early diagnosis will be of great significance for preventing and treating postpartum depression and avoiding the serious adverse consequences of postpartum depression. SUMMARY
[0006] In view of the above defects or improvement needs of the prior art, the application provides application of HNRNPA2B1 gene expression level detection substance in postpartum depression detection and a detection system, which aims to help early diagnosis and diagnosis of postpartum depression through non-invasive quantitative detection, strengthen intervention on postpartum depression, and thus avoid the serious adverse effects of postpartum depression on mothers and infants.
[0007] To achieve the above-mentioned purpose, the application proposes the following solutions:
[0008] Application of HNRNPA2B1 gene expression level detection substance in preparation of a postpartum depression detection product.
[0009] wherein the sequence of the primer is
[0010] forward primer: 5'-TAGAGCACTGAGTGCAGTAACG-3',
[0011] reverse primer: 5'-CAGTAAGCTAGATCCACTGACGT-3'.
[0012] wherein the gene detection chip is GSE45603 chip.
[0013] The application of the combination of the HNRNPA2B1 gene expression level detection substance and the gene expression level detection substance of at least one of IL10, RAD51, UBA52, NHP2, and RPL13A in the preparation of a postpartum depression detection product.
[0014] The postpartum depression detection system comprises
[0015] The gene expression level acquisition module is configured to acquire an expression level parameter of the HNRNPA2B1 gene and provide the parameter to the judgment module.
[0016] The judgment module is configured to take the HNRNPA2B1 gene expression level parameter as an input of a linear classifier and judge whether the sample is from a postpartum depression patient.
[0017] Further, the postpartum depression detection reagent comprises one or more combinations of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 gene expression level detection reagents.
[0018] Preferably, the postpartum depression detection reagent comprises one or more combinations of HNRNPA2B1, FBL, and SPI1 gene expression level detection reagents.
[0019] Preferably, the postpartum depression detection reagent comprises HNRNPA2B1, FBL, and SPI1 gene expression level detection reagents.
[0020] Preferably, the postpartum depression detection reagent comprises a gene mRNA expression level detection reagent.
[0021] Preferably, the postpartum depression detection reagent comprises a GSE45603 chip.
[0022] Preferably, the postpartum depression detection reagent comprises HNRNPA2B1, FBL, and / or SPI1 gene methylation level detection reagents.
[0023] According to another aspect of the present invention, a postpartum depression detection system is provided, which includes a gene expression level acquisition module and a judgment module;
[0024] The gene expression level acquisition module is used to acquire the expression level of one or more genes among HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1, and provide it to the judgment module.
[0025] The judgment module uses the expression level of one or more genes among HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 as input to the classifier to determine whether the sample comes from a patient with postpartum depression.
[0026] Preferably, in the postpartum depression detection system, the gene expression level acquisition module is used to acquire the expression level of one or more genes among HNRNPA2B1, FBL, and SPI1.
[0027] Preferably, in the postpartum depression detection system, the gene expression level acquisition module is used to acquire the expression levels of HNRNPA2B1, FBL, and SPI1 genes.
[0028] One or more of the following gene expression level detection reagents—HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1—are used in combination to prepare a non-invasive quantitative detection reagent for postpartum depression.
[0029] In summary, compared with the prior art, the above-described technical solutions conceived by this invention can achieve the following beneficial effects:
[0030] The postpartum depression detection reagent provided by this invention is applied to a postpartum depression detection system. The test system shows that the area under the receiver operating characteristic (ROC) curves of the HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 genes all exceed 0.75. When the area under the curve reaches 0.7 to 0.9, it is considered to have high precision in clinical testing, and a value exceeding 0.9 indicates high precision. This reagent is very suitable as an early diagnostic reagent for postpartum depression.
[0031] The preferred approach utilizes the GSE45603 chip for high-throughput, non-invasive quantitative detection, enabling accurate quantitative assessment of postpartum depression. Furthermore, the preferred approach allows for more accurate assessment of the occurrence and progression of postpartum depression through detection of target gene methylation levels. Attached Figure Description
[0032] Figure 1 This is a graph showing the results of gene association network analysis related to postpartum depression in Example 2. Figure 1 A represents the first gene interaction module network; Figure 1 B represents the second gene interaction module network. Figure 1 C represents the third gene interaction module network;
[0033] Figure 2 Example 3 uses a postpartum depression detection system with different gene expression levels to observe the area under the ROC curve;
[0034] Figure 3 This is the result of the mouse modeling test for postpartum depression in Example 4;
[0035] Figure 4 This is the result of gene expression detection in mice with postpartum depression and normal controls in Example 4. Detailed Implementation
[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.
[0037] The postpartum depression detection reagent provided by this invention includes one or more combinations of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 gene expression level detection reagents.
[0038] Among them, HNRNPA2B1 gene is heterogeneous nuclear ribonucleoprotein A2 / B1 gene; IL10 gene is interleukin-10 gene; RAD51 gene is recombinase RAD51 gene; UBA52 gene is ubiquitin-ribosome fusion protein 52 gene; NHP2 is ribonucleoprotein 2 gene; RPL13A gene is ribosomal protein L13a housekeeping gene; FBL gene is fibrin gene; and SPI1 gene is Spi-1 proto-oncogene.
[0039] Statistical analysis showed that the mRNA expression levels of the above genes differed by more than two-fold between patients with postpartum depression and normal samples, with a significance level of less than 0.05. HNRNPA2B1, IL10, and RAD51 genes were located at the center of the same postpartum depression-related gene association network, potentially affecting the same metabolic pathway, with HNRNPA2B1 showing the most significant effect. UBA52, NHP2, RPL13A, and FBL were located at the centroid of the same postpartum depression-related gene association network, potentially affecting the same metabolic pathway, with FBL showing the most significant effect. The SPI1 gene was located at the center of another postpartum depression-related gene association network. Therefore, the combined study of HNRNPA2B1, FBL, and SPI1 showed a very clear difference in their mRNA expression levels between patients with postpartum depression and normal samples.
[0040] A detection system using the mRNA expression levels of these three genes as indicators was used to test 21 blood samples (16 samples from patients with postpartum depression and 5 normal control samples). The results showed that the area under the ROC curve was above 0.75, with the highest reaching 0.902. Since the three genes are located in different modules, the correlation between them is not strong. Using the combined indicator of the three genes can more accurately identify samples with postpartum depression.
[0041] The following is an example:
[0042] Example 1: Statistical analysis of differences in expression levels between normal controls and patients with postpartum depression
[0043] Data source: The differential gene expression data between patients with postpartum depression and normal controls were obtained from the GEO database (Gene Expression Omnibus) GSE45603 dataset, which included whole blood samples from 5 series of normal controls and 16 patients with postpartum depression. The samples were analyzed using the GPL10558 platform (Illumina HumanHT-12V4.0 expressionbeadchip).
[0044] The expression levels of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 in normal controls and patients with postpartum depression were analyzed using R software (version 3.6.2). The results showed significant differences in the expression levels of these genes in patients with postpartum depression (P < 0.05 and |expression difference| ≥ 0.2).
[0045] The expression differences and P-values of the target genes used in this invention: HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 are shown in the table below:
[0046]
[0047] The data above indicate that the expression levels of the aforementioned genes' mRNA differ significantly between postpartum depression samples and normal human samples.
[0048] Example 2: Gene Association Network Analysis of Postpartum Depression
[0049] Differentially expressed genes in postpartum depression, including HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1, were used for automated gene function annotation using the GO database. Functional and metabolic pathway analyses were performed using the DAVID database. The key molecular functions, involved biological processes, cellular components, and metabolic pathways of these genes were visualized. KEGG analysis was used to analyze the interactions between these genes and the disease and drugs. Results are as follows: Figure 1 As shown, the above-mentioned genes were all enriched in the top 5% of differentially expressed metabolic pathways in postpartum depression and normal controls in both GO and KEGG analyses, with statistical significance P values <0.01. This indicates that these genes play a crucial role in the metabolic pathways involved in postpartum depression.
[0050] To improve accuracy, the validity of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 genes as biochemical markers for postpartum depression was verified. GSEA analysis (GSEA version 4.0.3, http: / / software.broadinstitute.org / gsea / index.jsp) was used for gene enrichment analysis, and the p-values for the above genes were also <0.05. This verifies that the above genes are involved in metabolic pathways associated with postpartum depression and can be used as screening markers for postpartum depression. Furthermore, it was shown that high expression of the HNRNPA2B1 gene is associated with endocytosis, low expression of the FBL gene is associated with long-term inhibition in the brain, and low expression of the SPI1 gene is associated with cell proliferation.
[0051] Gene interaction analysis was performed on differentially expressed genes in normal controls and patients with postpartum depression using Cytoscape software. Interactions with a reliability score greater than 0.4 were selected to analyze relationships between differentially expressed genes. A total of 673 differentially expressed genes were imported into Cytoscape for analysis. Hub genes were retrieved using the CytoHubba plugin in Cytoscape. Hub genes were selected based on a degree algorithm, and the top 30 genes were defined as hub genes. The results showed that HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 were all within the top 30 hub genes. The hub gene scores are shown in the table below.
[0052]
[0053] Example 3: Postpartum Depression Detection System
[0054] A postpartum depression detection system includes a gene expression level acquisition module and a judgment module;
[0055] The gene expression level acquisition module is used to acquire the expression level of one or more genes among HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1, and provide it to the judgment module.
[0056] The judgment module uses the gene expression levels of HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, and SPI1 as inputs to a linear classifier to determine whether a sample comes from a patient with postpartum depression.
[0057] The GEO (Gene Expression Omnibus) dataset GSE45603 was used for testing, and receptivity curves (ROC curves) were plotted as follows: Figure 2 As shown in the table below:
[0058]
[0059] The above results confirm that the genes mentioned above, when used as markers for postpartum depression, can be effectively distinguished between postpartum depression samples and normal samples by their detection system, reaching a moderate level of effectiveness and making them suitable as clinical screening indicators.
[0060] Example 4: Animal Experiment Verification
[0061] This study used chronic pre-pregnancy stress to establish a mouse model of postpartum depression and evaluated the expression of HnRNPA2B1, Fibrillarin (FBL), and Spi-1 proto-oncogene (SPI1) genes in the whole blood of female mice. Seven-week-old Balb / c female mice were randomly divided into two groups: a blank control group receiving no stimulation and a control group subjected to chronic stress for three consecutive weeks. After the stress period, mice from both the blank control and stress groups were randomly mated and conceived together, resulting in two groups after delivery: a blank control group and a stress-plus-delivery group (the postpartum depression model group). Three weeks postpartum, the behavioral characteristics of the mice in each group were assessed, including forced swimming, sucrose preference, and tail suspension tests, to evaluate the success of the model establishment. Three weeks postpartum, whole blood samples were collected from the female mice in each group, and the expression of HnRNPA2B1, Fibrillarin (FBL), and Spi-1 proto-oncogene (SPI1) genes was detected using real-time quantitative PCR.
[0062] Behavioral testing results: After behavioral testing, it was found that the model was successfully established, and the results are as follows. Figure 3 As shown.
[0063] The primers used for gene expression level testing are shown in the table below:
[0064]
[0065] Gene expression: The mRNA expression levels of three genes in whole blood were detected by qRT-PCR. The results are as follows: Figure 4 As shown.
[0066] The results showed that the expression levels of the above-mentioned genes in mice with a postpartum depression model were significantly different from those in normal controls, confirming that the gene expression level detection reagents for the above-mentioned genes are suitable as detection reagents for postpartum depression.
[0067] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. Application of HNRNPA2B1 gene expression level detection material in the preparation of postpartum depression detection products.
2. The application according to claim 1, wherein, The gene expression level detection material is a gene mRNA expression level detection material, which includes primers or gene detection chips.
3. The application according to claim 2, wherein, The sequence of the primer is as follows: Forward primer: 5'-TAGAGCACTGAGTGCAGTAACG-3', Reverse primer: 5'-CAGTAAGCTAGATCCACTGACGT-3'.
4. The application according to claim 2, wherein, The gene detection chip is a GSE45603 chip.
5. Application of the combination of HNRNPA2B1 gene expression level detection substance and at least one of IL10, RAD51, UBA52, NHP2, and RPL13A gene expression level detection substances in the preparation of postpartum depression detection products.
6. The application according to claim 5, wherein, The gene expression level detection material is a gene mRNA expression level detection material.
7. A postpartum depression detection system, characterized in that, include The gene expression level acquisition module is used to acquire the expression level parameters of the HNRNPA2B1 gene in the sample and provide them to the judgment module. The judgment module uses the HNRNPA2B1 gene expression level parameter as input to a linear classifier to determine whether the sample comes from a patient with postpartum depression.
8. The postpartum depression detection system according to claim 7, characterized in that, Gene expression level detection refers to the detection of gene mRNA expression levels.