Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches
The impaired suppressive function of regulatory T cells is well-understood in systemic lupus erythematosus. This is likely due to changes in <i>Foxp<sub>3</sub></i> expression that are crucial for regulatory T-cell stability and function. There are a few reports on the correl...
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MDPI AG
2023-11-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/22/3442 |
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| author | Zahra Birjan Khalil Khashei Varnamkhasti Sara Parhoudeh Leila Naeimi Sirous Naeimi |
| author_facet | Zahra Birjan Khalil Khashei Varnamkhasti Sara Parhoudeh Leila Naeimi Sirous Naeimi |
| author_sort | Zahra Birjan |
| collection | DOAJ |
| description | The impaired suppressive function of regulatory T cells is well-understood in systemic lupus erythematosus. This is likely due to changes in <i>Foxp<sub>3</sub></i> expression that are crucial for regulatory T-cell stability and function. There are a few reports on the correlation between the <i>Foxp<sub>3</sub></i> altered expression level and single-nucleotide polymorphisms within the <i>Foxp<sub>3</sub></i> locus. Moreover, some studies showed the importance of <i>Foxp<sub>3</sub></i> expression in the same diseases. Therefore, to explore the possible effects of single-nucleotide polymorphisms, here, we evaluated the association of IVS9+459/rs2280883 (T>C) and −2383/rs3761549 (C>T) <i>Foxp<sub>3</sub></i> polymorphisms with systemic lupus erythematosus. Moreover, through machine-learning and deep-learning methods, we assessed the connection of the expression level of the gene with the disease. Single-nucleotide polymorphisms of <i>Foxp<sub>3</sub></i> (IVS9+459/rs2280883 (T>C) and −2383/rs3761549 (C>T)) were, respectively, genotyped using allele-specific PCR and direct sequencing and polymerase chain reaction-restriction fragment length polymorphism, in 199 systemic lupus erythematosus patients and 206 healthy age- and sex-matched controls. The Statistical Package for the Social Sciences version 19 and Fisher’s exact and chi-square tests were used to analyze the data. Moreover, six machine-learning models and two sequential deep-learning models were designed to classify patients from normal people in the E-MTAB-11191 dataset through the expression level of <i>Foxp<sub>3</sub></i> and its correlated genes. The allele and genotype frequencies of both polymorphisms in question were found to be significantly associated with an increased risk of systemic lupus erythematosus. Furthermore, both of the two single-nucleotide polymorphisms were associated with some systemic-lupus-erythematosus-related risk factors. Three SVM models and the logistic regression model showed an 81% accuracy in classification problems. In addition, the first deep-learning model showed an 83% and 89% accuracy for the training and validation data, respectively, while the second model had an 85% and 79% accuracy for the training and validation datasets. In this study, we are prompted to represent the predisposing loci for systemic lupus erythematosus pathogenesis and strived to provide evidence-based support to the application of machine learning for the identification of systemic lupus erythematosus. It is predicted that the recruiting of machine-learning algorithms with the simultaneous measurement of the applied single nucleotide polymorphisms will increased the diagnostic accuracy of systemic lupus erythematosus, which will be very helpful in providing sufficient predictive value about individual subjects with systemic lupus erythematosus. |
| first_indexed | 2024-03-09T16:53:28Z |
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| language | English |
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| publishDate | 2023-11-01 |
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| spelling | doaj.art-16d8d23290f840109cec4725592b56a62023-11-24T14:37:36ZengMDPI AGDiagnostics2075-44182023-11-011322344210.3390/diagnostics13223442Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental ApproachesZahra Birjan0Khalil Khashei Varnamkhasti1Sara Parhoudeh2Leila Naeimi3Sirous Naeimi4Department of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kazerun 73, IranDepartment of Medical Laboratory Sciences, Faculty of Medicine, Kazerun Branch, Islamic Azad University, Kazerun 73, IranDepartment of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kazerun 73, IranDepartment of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kazerun 73, IranDepartment of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kazerun 73, IranThe impaired suppressive function of regulatory T cells is well-understood in systemic lupus erythematosus. This is likely due to changes in <i>Foxp<sub>3</sub></i> expression that are crucial for regulatory T-cell stability and function. There are a few reports on the correlation between the <i>Foxp<sub>3</sub></i> altered expression level and single-nucleotide polymorphisms within the <i>Foxp<sub>3</sub></i> locus. Moreover, some studies showed the importance of <i>Foxp<sub>3</sub></i> expression in the same diseases. Therefore, to explore the possible effects of single-nucleotide polymorphisms, here, we evaluated the association of IVS9+459/rs2280883 (T>C) and −2383/rs3761549 (C>T) <i>Foxp<sub>3</sub></i> polymorphisms with systemic lupus erythematosus. Moreover, through machine-learning and deep-learning methods, we assessed the connection of the expression level of the gene with the disease. Single-nucleotide polymorphisms of <i>Foxp<sub>3</sub></i> (IVS9+459/rs2280883 (T>C) and −2383/rs3761549 (C>T)) were, respectively, genotyped using allele-specific PCR and direct sequencing and polymerase chain reaction-restriction fragment length polymorphism, in 199 systemic lupus erythematosus patients and 206 healthy age- and sex-matched controls. The Statistical Package for the Social Sciences version 19 and Fisher’s exact and chi-square tests were used to analyze the data. Moreover, six machine-learning models and two sequential deep-learning models were designed to classify patients from normal people in the E-MTAB-11191 dataset through the expression level of <i>Foxp<sub>3</sub></i> and its correlated genes. The allele and genotype frequencies of both polymorphisms in question were found to be significantly associated with an increased risk of systemic lupus erythematosus. Furthermore, both of the two single-nucleotide polymorphisms were associated with some systemic-lupus-erythematosus-related risk factors. Three SVM models and the logistic regression model showed an 81% accuracy in classification problems. In addition, the first deep-learning model showed an 83% and 89% accuracy for the training and validation data, respectively, while the second model had an 85% and 79% accuracy for the training and validation datasets. In this study, we are prompted to represent the predisposing loci for systemic lupus erythematosus pathogenesis and strived to provide evidence-based support to the application of machine learning for the identification of systemic lupus erythematosus. It is predicted that the recruiting of machine-learning algorithms with the simultaneous measurement of the applied single nucleotide polymorphisms will increased the diagnostic accuracy of systemic lupus erythematosus, which will be very helpful in providing sufficient predictive value about individual subjects with systemic lupus erythematosus.https://www.mdpi.com/2075-4418/13/22/3442systemic lupus erythematosuspolymorphism<i>Foxp<sub>3</sub></i><i>rs2280883</i><i>rs3761549</i>machine learning |
| spellingShingle | Zahra Birjan Khalil Khashei Varnamkhasti Sara Parhoudeh Leila Naeimi Sirous Naeimi Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches Diagnostics systemic lupus erythematosus polymorphism <i>Foxp<sub>3</sub></i> <i>rs2280883</i> <i>rs3761549</i> machine learning |
| title | Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches |
| title_full | Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches |
| title_fullStr | Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches |
| title_full_unstemmed | Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches |
| title_short | Crucial Role of <i>Foxp<sub>3</sub></i> Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches |
| title_sort | crucial role of i foxp sub 3 sub i gene expression and mutation in systemic lupus erythematosus inferred from computational and experimental approaches |
| topic | systemic lupus erythematosus polymorphism <i>Foxp<sub>3</sub></i> <i>rs2280883</i> <i>rs3761549</i> machine learning |
| url | https://www.mdpi.com/2075-4418/13/22/3442 |
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