Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy

Objective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms.Methods: Our study included t...

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Main Authors: Xueqin Zhang, Peng Chao, Hong Jiang, Shufen Yang, Gulimire Muhetaer, Jun Zhang, Xue Song, Chen Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.975521/full
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author Xueqin Zhang
Peng Chao
Hong Jiang
Shufen Yang
Gulimire Muhetaer
Jun Zhang
Xue Song
Chen Lu
author_facet Xueqin Zhang
Peng Chao
Hong Jiang
Shufen Yang
Gulimire Muhetaer
Jun Zhang
Xue Song
Chen Lu
author_sort Xueqin Zhang
collection DOAJ
description Objective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms.Methods: Our study included three gene expression datasets of IgA nephropathy (GSE37460, GSE73953, GSE93798). Differential expression of RBPs between IgA nephropathy and normal samples was analyzed via limma, and hub RBPs were determined through MCODE. Afterwards, three machine learning algorithms (LASSO, SVM-RFE, random forest) were integrated to determine characteristic RBPs, which were verified in the Nephroseq database. Immune cell infiltrations were estimated through CIBERSORT. Utilizing ConsensusClusterPlus, IgA nephropathy were classified based on hub RBPs. The potential upstream miRNAs were predicted.Results: Among 388 RBPs with differential expression, 43 hub RBPs were determined. After integration of three machine learning algorithms, three characteristic RBPs were finally identified (DDX27, RCL1, and TFB2M). All of them were down-regulated in IgA nephropathy than normal specimens, with the excellent diagnostic efficacy. Additionally, they were significantly linked to immune cell infiltrations, immune checkpoints, and pyroptosis-relevant genes. Based on hub RBPs, IgA nephropathy was stably classified as two subtypes (cluster 1 and 2). Cluster 1 exhibited the relatively high expression of pyroptosis-relevant genes and characteristic RBPs. MiR-501-3p, miR-760, miR-502-3p, miR-1224-5p, and miR-107 were potential upstream miRNAs of hub RBPs.Conclusion: Collectively, our findings determine three characteristic RBPs in IgA nephropathy and two RBPs-based subtypes, and thus provide a certain basis for further research on the diagnosis and pathogenesis of IgA nephropathy.
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spelling doaj.art-4a5d7994f3e34789b94379eb25e8e3c62022-12-22T03:48:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.975521975521Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathyXueqin Zhang0Peng Chao1Hong Jiang2Shufen Yang3Gulimire Muhetaer4Jun Zhang5Xue Song6Chen Lu7Department of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDepartment of Nephrology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaObjective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms.Methods: Our study included three gene expression datasets of IgA nephropathy (GSE37460, GSE73953, GSE93798). Differential expression of RBPs between IgA nephropathy and normal samples was analyzed via limma, and hub RBPs were determined through MCODE. Afterwards, three machine learning algorithms (LASSO, SVM-RFE, random forest) were integrated to determine characteristic RBPs, which were verified in the Nephroseq database. Immune cell infiltrations were estimated through CIBERSORT. Utilizing ConsensusClusterPlus, IgA nephropathy were classified based on hub RBPs. The potential upstream miRNAs were predicted.Results: Among 388 RBPs with differential expression, 43 hub RBPs were determined. After integration of three machine learning algorithms, three characteristic RBPs were finally identified (DDX27, RCL1, and TFB2M). All of them were down-regulated in IgA nephropathy than normal specimens, with the excellent diagnostic efficacy. Additionally, they were significantly linked to immune cell infiltrations, immune checkpoints, and pyroptosis-relevant genes. Based on hub RBPs, IgA nephropathy was stably classified as two subtypes (cluster 1 and 2). Cluster 1 exhibited the relatively high expression of pyroptosis-relevant genes and characteristic RBPs. MiR-501-3p, miR-760, miR-502-3p, miR-1224-5p, and miR-107 were potential upstream miRNAs of hub RBPs.Conclusion: Collectively, our findings determine three characteristic RBPs in IgA nephropathy and two RBPs-based subtypes, and thus provide a certain basis for further research on the diagnosis and pathogenesis of IgA nephropathy.https://www.frontiersin.org/articles/10.3389/fgene.2022.975521/fullIgA nephropathyRNA binding proteinsmachine learningdiagnosissubtypesimmunity
spellingShingle Xueqin Zhang
Peng Chao
Hong Jiang
Shufen Yang
Gulimire Muhetaer
Jun Zhang
Xue Song
Chen Lu
Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
Frontiers in Genetics
IgA nephropathy
RNA binding proteins
machine learning
diagnosis
subtypes
immunity
title Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
title_full Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
title_fullStr Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
title_full_unstemmed Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
title_short Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy
title_sort integration of three machine learning algorithms identifies characteristic rna binding proteins linked with diagnosis immunity and pyroptosis of iga nephropathy
topic IgA nephropathy
RNA binding proteins
machine learning
diagnosis
subtypes
immunity
url https://www.frontiersin.org/articles/10.3389/fgene.2022.975521/full
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