Decoding the mitochondrial connection: development and validation of biomarkers for classifying and treating systemic lupus erythematosus through bioinformatics and machine learning

Li, Haoguang; Zhou, Lu; Zhou, Wei; Zhang, Xiuling; Shang, Jingjing; Feng, Xueqin; Yu, Le; Fan, Jie; Ren, Jie; Zhang, Rongwei; Duan, Xinwang

doi:10.1186/s41927-023-00369-0

Cited by 20 publications

(1 citation statement)

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“…Two recent bioinformatics studies have suggested that Fam210b is an important candidate for the classification and therapeutic targeting of SLE [16,17]. To prove the role of Fam210b in SLE via experimental methods, we constructed mice with Fam210b knockout and found that Fam210b knockout leads to a low probability of lupus-like symptoms in mice.…”

Section: Introductionmentioning

confidence: 99%

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

Xu,

Gao,

Zhang

et al. 2024

IJMS

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Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b−/−) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b−/− mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

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Section: Introductionmentioning

confidence: 99%

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

Xu,

Gao,

Zhang

et al. 2024

IJMS

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Elucidating key immunological biomarkers and immune microenvironment dynamics in aging‐related intracranial aneurysm through integrated multi‐omics analysis

Wang,

Xiao,

Zhang

et al. 2024

Environmental Toxicology

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BackgroundThe exact cause of intracranial aneurysms (IA) is still unclear. However, pro‐inflammatory factors are known to contribute to IA progression. The specific changes in the immune microenvironment of IAs remain largely unexplored.MethodsThis study analyzed single‐cell sequencing data from a male mouse model of brain aneurysm, focusing on samples before and after elastase‐induced Willis aneurysms. The data helped identify eight distinct cell subpopulations: fibroblasts, macrophages, NK cells, endothelial cells, B cells, granulocytes, and monocytes. The study also involved bulk RNA sequencing of 97 IA samples, utilizing ssGSEA and CIBERSORT algorithms for analysis. Intercellular communication among these cells was inferred to understand the immune dynamics in IA.ResultsThe study found that fibroblasts and macrophages are predominant in various disease states of IA. Notably, the onset of IA was marked by a significant increase in fibroblasts and a decrease in macrophages. There was a marked increase in cellular interactions, especially involving macrophages, at the onset of the disease. Through enrichment analysis, 12 potential immunogenic biomarkers were identified. Of these, Rgs1 emerged as a critical molecule in IA formation, confirmed through secondary validation in a single‐cell sequencing dataset.ConclusionThis comprehensive analysis of immune cell composition and intercellular communication in IA tissues highlights the significant roles of macrophages and the molecule Rgs1. These findings shed light on the physiological and pathological conditions of IA, offering new insights into its immune microenvironment.

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Exploring m6A‐linked aging genes in osteoarthritis and broad cancer spectrum: Prospects for diagnostic and therapeutic advancements

Cai,

Xia,

et al. 2024

Environmental Toxicology

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Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6‐methyladenosine (m6A)‐related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A‐related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A‐related aging genes. Utilizing XGBoost, a cutting‐edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A‐related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real‐time polymerase chain reaction analyses on two cell lines: HC‐OA (representing adult osteoarthritis cells) and C‐28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A‐related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.

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Decoding the mitochondrial connection: development and validation of biomarkers for classifying and treating systemic lupus erythematosus through bioinformatics and machine learning

Cited by 20 publications

References 64 publications

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

Elucidating key immunological biomarkers and immune microenvironment dynamics in aging‐related intracranial aneurysm through integrated multi‐omics analysis

Exploring m6A‐linked aging genes in osteoarthritis and broad cancer spectrum: Prospects for diagnostic and therapeutic advancements

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