Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure

Patients with rheumatoid arthritis (RA) have an increased risk of ischemic heart failure (IHF), but the shared mechanisms are unclear. This study analyzed RNA sequencing data from five RA and IHF datasets to identify common biological mechanisms and significant biomarkers. One hundred and seventy-se...

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Main Authors: Ziyi Sun, Jianguo Lin, Xiaoning Sun, Zhangjun Yun, Xiaoxiao Zhang, Siyu Xu, Jinlong Duan, Kuiwu Yao
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844025000209
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author Ziyi Sun
Jianguo Lin
Xiaoning Sun
Zhangjun Yun
Xiaoxiao Zhang
Siyu Xu
Jinlong Duan
Kuiwu Yao
author_facet Ziyi Sun
Jianguo Lin
Xiaoning Sun
Zhangjun Yun
Xiaoxiao Zhang
Siyu Xu
Jinlong Duan
Kuiwu Yao
author_sort Ziyi Sun
collection DOAJ
description Patients with rheumatoid arthritis (RA) have an increased risk of ischemic heart failure (IHF), but the shared mechanisms are unclear. This study analyzed RNA sequencing data from five RA and IHF datasets to identify common biological mechanisms and significant biomarkers. One hundred and seventy-seven common differentially expressed genes (CDEGs) were identified, with enrichment analysis highlighting pathways related to sarcomere organization, ventricular myocardial tissue morphogenesis, chondrocyte differentiation, prolactin signaling, hematopoietic cell lineage, and protein methyltransferases. Five hub genes (CD2, CD3D, CCL5, IL7R, and SPATA18) were identified through protein-protein interaction (PPI) network analysis and machine learning. Co-expression and immune cell infiltration analyses underscored the importance of the inflammatory immune response, with hub genes showing significant correlations with plasma cells, activated CD4+ T memory cells, monocytes, and T regulatory cells. Single-cell RNA sequencing (scRNA-seq) confirmed hub gene expression primarily in T cells, activated T cells, monocytes, and NK cells. The findings underscore the critical roles of sarcomere organization, prolactin signaling, protein methyltransferase activity, and immune responses in the progression of IHF in RA patients. These insights not only identify valuable biomarkers and therapeutic targets but also offer promising directions for early diagnosis, personalized treatments, and preventive strategies for IHF in the context of RA. Moreover, the results highlight opportunities for repurposing existing drugs and developing new therapeutic interventions, which could reduce the risk of IHF in RA patients and improve their overall prognosis.
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spelling doaj-art-4555c2f780804190a8ac0de8fc339a0a2025-02-02T05:27:55ZengElsevierHeliyon2405-84402025-01-01112e41641Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failureZiyi Sun0Jianguo Lin1Xiaoning Sun2Zhangjun Yun3Xiaoxiao Zhang4Siyu Xu5Jinlong Duan6Kuiwu Yao7Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of China; Graduate School, Beijing University of Chinese Medicine, No.11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of ChinaGraduate School, Beijing University of Chinese Medicine, No.11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of China; Graduate School, Beijing University of Chinese Medicine, No.11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of ChinaGuang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of China; Academic Administration Office, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Inside Dongzhimen, Dongcheng District, Beijing, 100700, People's Republic of China; Corresponding author: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiangge, Xicheng District, Beijing, 100053, People's Republic of China.Patients with rheumatoid arthritis (RA) have an increased risk of ischemic heart failure (IHF), but the shared mechanisms are unclear. This study analyzed RNA sequencing data from five RA and IHF datasets to identify common biological mechanisms and significant biomarkers. One hundred and seventy-seven common differentially expressed genes (CDEGs) were identified, with enrichment analysis highlighting pathways related to sarcomere organization, ventricular myocardial tissue morphogenesis, chondrocyte differentiation, prolactin signaling, hematopoietic cell lineage, and protein methyltransferases. Five hub genes (CD2, CD3D, CCL5, IL7R, and SPATA18) were identified through protein-protein interaction (PPI) network analysis and machine learning. Co-expression and immune cell infiltration analyses underscored the importance of the inflammatory immune response, with hub genes showing significant correlations with plasma cells, activated CD4+ T memory cells, monocytes, and T regulatory cells. Single-cell RNA sequencing (scRNA-seq) confirmed hub gene expression primarily in T cells, activated T cells, monocytes, and NK cells. The findings underscore the critical roles of sarcomere organization, prolactin signaling, protein methyltransferase activity, and immune responses in the progression of IHF in RA patients. These insights not only identify valuable biomarkers and therapeutic targets but also offer promising directions for early diagnosis, personalized treatments, and preventive strategies for IHF in the context of RA. Moreover, the results highlight opportunities for repurposing existing drugs and developing new therapeutic interventions, which could reduce the risk of IHF in RA patients and improve their overall prognosis.http://www.sciencedirect.com/science/article/pii/S2405844025000209Rheumatoid arthritisIschemic heart failureMicroarrayMachine learningSingle-cell
spellingShingle Ziyi Sun
Jianguo Lin
Xiaoning Sun
Zhangjun Yun
Xiaoxiao Zhang
Siyu Xu
Jinlong Duan
Kuiwu Yao
Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
Heliyon
Rheumatoid arthritis
Ischemic heart failure
Microarray
Machine learning
Single-cell
title Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
title_full Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
title_fullStr Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
title_full_unstemmed Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
title_short Bioinformatics combining machine learning and single-cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
title_sort bioinformatics combining machine learning and single cell sequencing analysis to identify common mechanisms and biomarkers of rheumatoid arthritis and ischemic heart failure
topic Rheumatoid arthritis
Ischemic heart failure
Microarray
Machine learning
Single-cell
url http://www.sciencedirect.com/science/article/pii/S2405844025000209
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