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      Identification of useful genes from multiple microarrays for ulcerative colitis diagnosis based on machine learning methods

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          Abstract

          Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with an increasing incidence and prevalence worldwide. The diagnosis for UC mainly relies on clinical symptoms and laboratory examinations. As some previous studies have revealed that there is an association between gene expression signature and disease severity, we thereby aim to assess whether genes can help to diagnose UC and predict its correlation with immune regulation. A total of ten eligible microarrays (including 387 UC patients and 139 healthy subjects) were included in this study, specifically with six microarrays (GSE48634, GSE6731, GSE114527, GSE13367, GSE36807, and GSE3629) in the training group and four microarrays (GSE53306, GSE87473, GSE74265, and GSE96665) in the testing group. After the data processing, we found 87 differently expressed genes. Furthermore, a total of six machine learning methods, including support vector machine, least absolute shrinkage and selection operator, random forest, gradient boosting machine, principal component analysis, and neural network were adopted to identify potentially useful genes. The synthetic minority oversampling (SMOTE) was used to adjust the imbalanced sample size for two groups (if any). Consequently, six genes were selected for model establishment. According to the receiver operating characteristic, two genes of OLFM4 and C4BPB were finally identified. The average values of area under curve for these two genes are higher than 0.8, either in the original datasets or SMOTE-adjusted datasets. Besides, these two genes also significantly correlated to six immune cells, namely Macrophages M1, Macrophages M2, Mast cells activated, Mast cells resting, Monocytes, and NK cells activated ( P  <  0.05). OLFM4 and C4BPB may be conducive to identifying patients with UC. Further verification studies could be conducted.

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          Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease

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            American Gastroenterological Association Institute Guideline on the Management of Mild-to-Moderate Ulcerative Colitis

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              Diagnosis of ulcerative colitis before onset of inflammation by multivariate modeling of genome-wide gene expression data.

              Endoscopically obtained mucosal biopsies play an important role in the differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD), but in some cases where neither macroscopic nor microscopic signs of inflammation are present the biopsies provide only inconclusive information. Previous studies indicate that CD cannot be diagnosed by molecular and histological diagnostic tools using colonic biopsies without microscopic signs of inflammation, but it is unknown if this is also the case for UC. The aim of the present study was to apply multivariate modeling of genome-wide gene expression to investigate if a diagnosable preinflammatory state exists in biopsies of noninflamed UC colon, and to exploit such information to build a diagnostic tool. Genome-wide gene expression data were obtained from control subjects and UC and CD patients. In total, 89 biopsies from 78 patients were included. A diagnostic model was derived with the random forest method based on 71 biopsies from 60 patients. The model-internal out-of-bag performance measure yielded perfect classification. Furthermore, the model was validated in independent 18 noninflamed biopsies from 18 patients (7 UC, 7 CD, 4 control) where the model achieved 100% sensitivity (95% confidence limits: 60.0-100) and 100% specificity (95% confidence limits: 71.5-100). The present study demonstrates a preinflammatory state in patients diagnosed with UC. In addition, we demonstrate the usefulness of random forest modeling of genome-wide gene expression data for distinguishing quiescent and active UC colonic mucosa versus control and CD colonic mucosa.
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                Author and article information

                Contributors
                zhangxuan@hkbu.edu.hk
                bzxiang@hkbu.edu.hk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                15 June 2022
                15 June 2022
                2022
                : 12
                : 9962
                Affiliations
                [1 ]GRID grid.410648.f, ISNI 0000 0001 1816 6218, Tianjin University of Traditional Chinese Medicine, ; Tianjin, China
                [2 ]GRID grid.221309.b, ISNI 0000 0004 1764 5980, Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, Chinese EQUATOR Centre, School of Chinese Medicine, , Hong Kong Baptist University, ; Hong Kong, SAR China
                [3 ]GRID grid.221309.b, ISNI 0000 0004 1764 5980, Department of Computer Science, HKBU Faculty of Science, , Hong Kong Baptist University, ; Hong Kong, SAR China
                [4 ]GRID grid.410648.f, ISNI 0000 0001 1816 6218, Oncology Department, , The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, ; Tianjin, China
                [5 ]GRID grid.221309.b, ISNI 0000 0004 1764 5980, Centre for Chinese Herbal Medicine Drug Development, , Hong Kong Baptist University, ; Hong Kong, SAR China
                Article
                14048
                10.1038/s41598-022-14048-6
                9200771
                35705632
                264f2f2a-0d83-438d-906c-bfdd919a1d99
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 March 2022
                : 31 May 2022
                Funding
                Funded by: China Center for Evidence Based Traditional Chinese Medicine, CCEBTM
                Award ID: 2020YJSZX-5
                Award ID: 2020YJSZX-5
                Award ID: 2020YJSZX-5
                Award ID: 2020YJSZX-5
                Funded by: Health@InnoHK Initiative Fund of the Hong Kong Special Administrative Region Government
                Award ID: ITC RC/IHK/4/7
                Award ID: ITC RC/IHK/4/7
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                genetics,gastroenterology
                Uncategorized
                genetics, gastroenterology

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