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      Identification of disulfidptosis-related genes and subgroups in Alzheimer’s disease

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          Abstract

          Background

          Alzheimer’s disease (AD), a common neurological disorder, has no effective treatment due to its complex pathogenesis. Disulfidptosis, a newly discovered type of cell death, seems to be closely related to the occurrence of various diseases. In this study, through bioinformatics analysis, the expression and function of disulfidptosis-related genes (DRGs) in Alzheimer’s disease were explored.

          Methods

          Differential analysis was performed on the gene expression matrix of AD, and the intersection of differentially expressed genes and disulfidptosis-related genes in AD was obtained. Hub genes were further screened using multiple machine learning methods, and a predictive model was constructed. Finally, 97 AD samples were divided into two subgroups based on hub genes.

          Results

          In this study, a total of 22 overlapping genes were identified, and 7 hub genes were further obtained through machine learning, including MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, and GYS1. Furthermore, the diagnostic capability was validated using external datasets and clinical samples. Based on these genes, a predictive model was constructed, with a large area under the curve (AUC = 0.8847), and the AUCs of the two external validation datasets were also higher than 0.7, indicating the high accuracy of the predictive model. Using unsupervised clustering based on hub genes, 97 AD samples were divided into Cluster1 ( n = 24) and Cluster2 ( n = 73), with most hub genes expressed at higher levels in Cluster2. Immune infiltration analysis revealed that Cluster2 had a higher level of immune infiltration and immune scores.

          Conclusion

          A close association between disulfidptosis and Alzheimer’s disease was discovered in this study, and a predictive model was established to assess the risk of disulfidptosis subtype in AD patients. This study provides new perspectives for exploring biomarkers and potential therapeutic targets for Alzheimer’s disease.

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          Most cited references53

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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            limma powers differential expression analyses for RNA-sequencing and microarray studies

            limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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              GSVA: gene set variation analysis for microarray and RNA-Seq data

              Background Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. Results To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. Conclusions GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                04 August 2023
                2023
                : 15
                : 1236490
                Affiliations
                [1] 1The First Affiliated Hospital of Anhui University of Chinese Medicine , Hefei, China
                [2] 2Encephalopathy Center, The First Affiliated Hospital of Anhui University of Chinese Medicine , Hefei, China
                Author notes

                Edited by: Jiehui Jiang, Shanghai University, China

                Reviewed by: Hualin Chen, Peking Union Medical College Hospital (CAMS), China; Chao Cheng, Wuxi People’s Hospital of Nanjing Medical University, China

                *Correspondence: Daojun Xie, daojunxie@ 123456ahtcm.edu.cn
                Article
                10.3389/fnagi.2023.1236490
                10436325
                37600517
                31cbf768-6ed9-445d-9bd2-23fd75fd81f7
                Copyright © 2023 Ma, Wang and Xie.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 June 2023
                : 17 July 2023
                Page count
                Figures: 10, Tables: 1, Equations: 0, References: 53, Pages: 14, Words: 6811
                Funding
                This research was supported by the National Natural Science Foundation of China (No. 8187140739).
                Categories
                Neuroscience
                Original Research
                Custom metadata
                Alzheimer’s Disease and Related Dementias

                Neurosciences
                alzheimer’s disease,disulfidptosis,molecular clusters,machine learning,prediction model

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