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pmid:36619718
Identification of Immune-Related Genes and Small-Molecule Drugs in Interstitial Cystitis/Bladder Pain Syndrome Based on the Integrative Machine Learning Algorithms and Molecular Docking.
Yiheng Jiang · Xinqing Zhu · Abdullah Y Al-Danakh · Qiwei Chen · Deyong Yang
Journal of immunology research · 2022 doi:10.1155/2022/2069756
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Experiment
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Complete file
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The origin and pathophysiology of IC/BPS are currently unclear, making it difficult to diagnose and formulate successful treatments. Our study is aimed at investigating the role of immune-related genes in the diagnosis, progression, and therapy of IC/BPS.\nMethod: The gene expression datasets GSE11783, GSE11839, GSE28242, and GSE57560 were retrieved from the GEO database for further analysis. Immune-related IC/BPS differentially expressed genes (DEGs) were identified by limma. Three distinct machine learning approaches, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), were used to find the immune-related IC characteristic genes. Nomogram and receiving operator curves (ROC) were plotted to measure characteristic effectiveness. Using the CMap database and the molecular docking approach, potential small-molecule medicines were found and verified. Consensus cluster analysis was also performed to separate the IC/BPS samples into immunological subtypes.\nResults: A total of 24 immune-related IC/BPS-DEGs were identified. When compared to the normal control group, the IC/BPS cohort had significantly more immune cell infiltration. Integrative machine learning methods discovered 5 IC/BPS characteristic genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) that may predict IC/BPS diagnosis and immune cell infiltration. Furthermore, two immunological subgroups with substantial variations in immune cell infiltration across IC/BPS samples were identified, which were named cluster1 and cluster2, with the hallmark genes having greater expression in cluster2. Finally, bumetanide was shown to have the potential to be a medication for the treatment of IC/BPS, and it performed well in terms of its molecular binding with RASGRP1.\nConclusion: We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes. In addition, bumetanide was discovered to be a potential drug for treating IC/BPS, which may provide new insight into the diagnosis and immune therapy of IC/BPS patients.", "claims": [{"id": "claim-method", "statement": "Firstly, to identify IC/BPS differentially expressed genes (DEGs), a differential analysis was performed between 37 IC/BPS samples and 20 normal control samples using the R package limma (the cutoff score was set asp < 0.05 and absolute (log 2 FC) > 1.0) and was conducted to select IC/BPS differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36619718", "locator": "sections[4] \"2.2. Analysis of Immune-Related IC/BPS-DEGs\" paragraph 2", "quote": "Firstly, to identify IC/BPS differentially expressed genes (DEGs), a differential analysis was performed between 37 IC/BPS samples and 20 normal control samples using the R package limma (the cutoff score was set asp < 0.05 and absolute (log 2 FC) > 1.0) and was conducted to select IC/BPS differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original data presented in this study can be found in online repositories. Contact the corresponding authors for further inquiries.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36619718", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The original data presented in this study can be found in online repositories. Contact the corresponding authors for further inquiries."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36619718", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36619718"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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