Crohn disease biomarker, kit and screening method of biomarker

A biomarker, Crohn's disease technology, applied in the field of Crohn's disease biomarkers, kits and biomarker screening, can solve problems such as staying in, and achieve accurate results, high accuracy, and specificity high effect

Active Publication Date: 2022-04-12
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, research on the diagnosis of Crohn's disease based on gut microbiota sequencing data is still at the stage based on microbial abundance, which has certain limitations

Method used

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  • Crohn disease biomarker, kit and screening method of biomarker
  • Crohn disease biomarker, kit and screening method of biomarker
  • Crohn disease biomarker, kit and screening method of biomarker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Example 1 Screening of markers for non-invasive diagnosis of Crohn's disease based on microbial homologous genes and construction of diagnostic models

[0072] 1.1. Data collection

[0073] From the National Institutes of Health Human Microbiome Project IBDMDB database (URL: https: / / ibdmdb.org), the US National Center for Biotechnology Information SRA database (URL: https: / / www.ncbi.nlm.nih.gov / sra ) and the European Bioinformatics Institute ENA database (website: https: / / www.ebi.ac.uk / ena) to obtain fecal microbial metagenomic sequencing data and clinical information data (clinical information Mainly including: disease status, age, sex and BMI).

[0074] The cohorts included in this example are: PRJNA398089, PRJNA389280, PRJNA400072, PRJNA385949, SRP057027; the number of samples included in the actual analysis is 1148, including 745 samples of Crohn's disease and 403 healthy controls.

[0075] 1.2. Data preprocessing

[0076] Quality control of the sequencing data w...

Embodiment 2

[0091] Example 2 Different cohort cross-validation and leave-one-out method validation

[0092] Experimental materials: Cross-validation and leave-one-out validation using public data from different cohorts to test the robustness and versatility of microbial biomarkers.

[0093] experimental method:

[0094] 2.1, 10-fold cross-validation within different cohorts

[0095]For public data from different cohorts, based on our identified optimal microbial homologous gene combinations (celB, nirK, lpxR, dadA, cshB, impH, manZ, ABCC-BAC, K03710, comFA, actP, E2.4.1.5, C5AP, thiK, ezrA, truC, czcA, a total of 17 homologous genes), carry out internal 10-fold cross-validation for each cohort, that is, each cohort is randomly divided into 10 folds, each fold is used as a test set in turn, and the remaining The 9 folds are used as the training set for model building, and the average AUC of 10 folds is obtained.

[0096] 2.2 Cross-validation between different cohorts

[0097] For the p...

Embodiment 3

[0100] Example 3 specificity verification

[0101] Experimental materials: Collect the sequencing data of intestinal disease microorganisms other than Crohn's disease in the database for specificity verification, including colorectal cancer (PRJEB27928, the number of disease samples is 22, and the number of healthy control samples is 60), Alzheimer's Momo (cohort PRJEB17784, the number of disease samples is 30, the number of healthy control samples is 28), type 2 diabetes (cohort PRJEB1786, the number of disease samples is 53, the number of healthy control samples is 43) and liver cirrhosis (cohort PRJEB6337, the number of disease samples is 126, and the number of healthy control samples was 94).

[0102] Experimental method: For the sequencing data of different diseases, based on the optimal combination of homologous gene markers confirmed by us, a model was constructed for each disease, and the result of 10-fold cross-validation was obtained, that is, each disease data was r...

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Abstract

The invention discloses a Crohn's disease biomarker, a kit and a screening method of the biomarker. The Crohn's disease biomarker comprises microorganism homologous genes of which the KO numbers are K02761, K00368, K09953, K00285, K18692, K11895, K02796, K06148, K03710, K02240, K14393, K00689, K08652, K07251, K06286, K06175 and K15726, and a screening method of the kit. The screening method of the Crohn disease biomarker comprises the following steps: S1, acquiring microorganism sequencing data and clinical information data of a disease control group and a normal control group, and preprocessing; s2, screening the preprocessed microorganism sequencing data, and quantifying and annotating a microorganism homologous gene KO; s3, performing difference analysis on the microorganism homologous gene data of the disease patient and the healthy control group to obtain microorganism homologous genes with significant difference; s4, screening the differential homologous genes, and determining an optimal biomarker of the homologous genes; in conclusion, the Crohn disease biomarker and the screening method provided by the invention have the advantages of convenience in sampling, noninvasive property and higher clinical value.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a Crohn's disease biomarker, a kit and a screening method for the biomarker. Background technique [0002] Crohn's disease (CD) is a major form of inflammatory bowel disease characterized by skip lesions and transmural inflammation of the gastrointestinal tract. In the past two decades, the incidence of CD has been increasing globally, imposing a huge economic burden on society. CD has a long and variable course that eventually develops penetrating or stenotic complications. Unfortunately, existing technologies still cannot completely cure CD. Clinically, the standard diagnosis of CD mainly relies on endoscopic and imaging findings. However, the insidious and nonspecific symptoms of CD may lead to misdiagnosis at the time of presentation. Furthermore, endoscopy is an invasive procedure, and its attendant risks and complicated colon preparation may lead to poor patient compli...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883C12Q1/689C12Q1/6895C12Q1/70G16B30/00G16B40/00G06N3/04G06N3/08G16H50/50
CPCY02A90/10
Inventor 朱瑞新高升
Owner TONGJI UNIV
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