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pmid:35495164

Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning.

Zhihang Jiang · Mengting Shao · Xinzhu Dai · Zhixin Pan · Dongmei Liu

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.865559

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complete

Experiment

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Data

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Analysis

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title
Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning.
doi
10.3389/fgene.2022.865559
pmid
35495164
authors array · 5 items
[0]
Zhihang Jiang
[1]
Mengting Shao
[2]
Xinzhu Dai
[3]
Zhixin Pan
[4]
Dongmei Liu
journal
Frontiers in genetics
year
2022
abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects several organs and causes variable clinical symptoms. Exploring new insights on genetic factors may help reveal SLE etiology and improve the survival of SLE patients. The current study is designed to identify key genes involved in SLE and develop potential diagnostic biomarkers for SLE in clinical practice. Expression data of all genes of SLE and control samples in GSE65391 and GSE72509 datasets were downloaded from the Gene Expression Omnibus (GEO) database. A total of 11 accurate differentially expressed genes (DEGs) were identified by the "limma" and "RobustRankAggreg" R package. All these genes were functionally associated with several immune-related biological processes and a single KEGG (Kyoto Encyclopedia of Genes and Genome) pathway of necroptosis. The PPI analysis showed that IFI44, IFI44L, EIF2AK2, IFIT3, IFITM3, ZBP1, TRIM22, PRIC285, XAF1, and PARP9 could interact with each other. In addition, the expression patterns of these DEGs were found to be consistent in GSE39088. Moreover, Receiver operating characteristic (ROC) curves analysis indicated that all these DEGs could serve as potential diagnostic biomarkers according to the area under the ROC curve (AUC) values. Furthermore, we constructed the transcription factor (TF)-diagnostic biomarker-microRNA (miRNA) network composed of 278 nodes and 405 edges, and a drug-diagnostic biomarker network consisting of 218 nodes and 459 edges. To investigate the relationship between diagnostic biomarkers and the immune system, we evaluated the immune infiltration landscape of SLE and control samples from GSE6539. Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort. Our findings may benefit the diagnosis of patients with SLE and guide in developing novel targeted therapy in treating SLE patients.
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Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively.
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sections[7] "Machine Learning" paragraph 2
quote
Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively.
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sections[19] "Data Availability Statement" paragraph 2
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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IFI44 was identified as the optimal diagnostic biomarker for SLE and validated in an independent cohort, with an AUC of 0.850, diagnostic sensitivity of 0.923, and diagnostic specificity of 0.850.
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Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort.
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sections[16] "Identification of Optimal Biomarkers in SLE" paragraph 5
quote
ROC curve analysis showed that AUC for IFI44 was 0.850 when distinguishing SLE patients from healthy controls, and the diagnostic sensitivity and specificity were 0.923 and 0.850, respectively (Figure 9C).
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IFI44 was identified as the optimal diagnostic biomarker for SLE and validated in an independent cohort, with an AUC of 0.850, diagnostic sensitivity of 0.923, and diagnostic specificity of 0.850.
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[281]
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[282]
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[283]
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[299]
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[300]
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[301]
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[302]
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[304]
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[308]
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[331]
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[332]
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[340]
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[341]
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[342]
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[343]
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[349]
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[350]
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[355]
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[359]
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[360]
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[362]
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[363]
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[364]
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[365]
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[366]
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[371]
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[372]
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[373]
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[374]
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[375]
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[376]
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[377]
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[378]
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[379]
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[380]
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[381]
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[382]
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[383]
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[384]
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[385]
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[386]
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[387]
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[388]
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[389]
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[390]
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[391]
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[392]
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[393]
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[394]
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[395]
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[396]
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[397]
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[398]
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[399]
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[400]
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[401]
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[402]
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[403]
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[404]
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[414]
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[415]
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[416]
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[418]
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[419]
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[423]
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[424]
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[425]
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[426]
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[427]
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[428]
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[429]
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[430]
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[431]
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[432]
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[433]
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[434]
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[435]
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[436]
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[437]
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[438]
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[440]
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[441]
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[442]
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[443]
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[444]
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[445]
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[446]
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[447]
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[448]
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[449]
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[450]
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[451]
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[452]
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[453]
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[454]
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[455]
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[456]
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[457]
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[458]
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[459]
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[460]
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[461]
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[462]
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[463]
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[464]
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[465]
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[466]
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[467]
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[468]
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[469]
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[470]
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[471]
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[472]
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[473]
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[474]
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[475]
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[476]
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[477]
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[478]
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[479]
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[480]
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[481]
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[482]
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[483]
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[484]
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[485]
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[486]
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[487]
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[488]
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[489]
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[490]
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[491]
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[492]
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[493]
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[494]
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[495]
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[496]
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[497]
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[498]
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[499]
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[500]
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[501]
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[502]
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[503]
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[504]
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[505]
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[506]
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[507]
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[508]
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[509]
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[510]
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[511]
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[512]
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[513]
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[514]
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[515]
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[516]
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[517]
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[518]
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[519]
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[520]
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[521]
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[522]
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[523]
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[524]
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[525]
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[526]
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[527]
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[528]
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[529]
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[530]
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[531]
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[532]
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[533]
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[534]
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[535]
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[536]
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[537]
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[538]
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[539]
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[540]
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[541]
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[542]
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[543]
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[544]
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[545]
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[546]
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[547]
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[548]
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[549]
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[550]
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[551]
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[552]
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[553]
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[554]
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[555]
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[556]
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[557]
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[558]
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[559]
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[560]
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[561]
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[562]
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[563]
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[564]
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[565]
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[566]
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[567]
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[568]
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[569]
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[570]
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[571]
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[572]
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[573]
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[574]
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[575]
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[576]
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[577]
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[578]
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[579]
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[580]
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[581]
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[582]
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[583]
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[584]
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[585]
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[586]
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[587]
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[588]
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[589]
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[590]
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[591]
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[592]
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[593]
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[594]
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[595]
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[596]
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[597]
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[598]
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[599]
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[600]
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[601]
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[602]
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[603]
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[604]
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[605]
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[606]
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[607]
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[608]
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[609]
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[610]
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[611]
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[612]
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[613]
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[614]
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[615]
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[616]
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[617]
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[618]
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[619]
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[620]
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[621]
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[622]
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[623]
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[624]
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[625]
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[626]
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[627]
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[628]
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[629]
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[630]
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[631]
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[632]
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[633]
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[634]
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[635]
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[636]
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[637]
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[638]
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[639]
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[640]
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[641]
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[642]
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[643]
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[644]
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[645]
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[646]
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[647]
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[648]
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[649]
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[650]
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[651]
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[652]
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[653]
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[654]
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[655]
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[656]
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[657]
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[658]
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[659]
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[660]
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[661]
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[662]
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[663]
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[664]
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[665]
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[666]
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[667]
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[668]
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[669]
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[670]
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[671]
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[672]
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[673]
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[674]
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[675]
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[676]
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[677]
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[678]
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[679]
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[680]
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[681]
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[682]
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[683]
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[684]
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[685]
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[686]
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[687]
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[688]
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[689]
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[690]
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[691]
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[692]
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[693]
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[694]
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[695]
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[696]
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[697]
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[698]
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[699]
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[700]
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[701]
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[702]
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[703]
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[704]
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[705]
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[706]
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[707]
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[708]
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[709]
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[710]
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[711]
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[712]
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[713]
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[714]
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[715]
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[716]
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[717]
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[718]
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[719]
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[720]
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[721]
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[722]
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[723]
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[724]
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[725]
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[726]
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[727]
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[728]
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[729]
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[730]
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[731]
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[732]
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[733]
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[734]
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[735]
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[736]
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[737]
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[738]
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[739]
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[740]
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[741]
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[742]
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[743]
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[744]
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[745]
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[746]
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[747]
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[748]
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[749]
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[750]
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[751]
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[752]
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[753]
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[754]
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[755]
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[756]
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[757]
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[758]
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[759]
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[760]
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[761]
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[762]
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[763]
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[764]
GSM1594991
[765]
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[766]
GSM1594993
[767]
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[768]
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[769]
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[770]
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[771]
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[772]
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[773]
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[774]
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[775]
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[776]
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[777]
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[778]
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[779]
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[780]
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[781]
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[782]
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[783]
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[784]
GSM1595011
[785]
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[786]
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[787]
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[788]
GSM1595015
[789]
GSM1595016
[790]
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[791]
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[792]
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[793]
GSM1595020
[794]
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[795]
GSM1595022
[796]
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[797]
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[798]
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[799]
GSM1595026
[800]
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[801]
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[802]
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[803]
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[804]
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[805]
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[806]
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[807]
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[808]
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[809]
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[810]
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[811]
GSM1595038
[812]
GSM1595039
[813]
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[814]
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[815]
GSM1595042
[816]
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[817]
GSM1595044
[818]
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[819]
GSM1595046
[820]
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[821]
GSM1595048
[822]
GSM1595049
[823]
GSM1595050
[824]
GSM1595051
[825]
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[826]
GSM1595053
[827]
GSM1595054
[828]
GSM1595055
[829]
GSM1595056
[830]
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[831]
GSM1595058
[832]
GSM1595059
[833]
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[834]
GSM1595061
[835]
GSM1595062
[836]
GSM1595063
[837]
GSM1595064
[838]
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[839]
GSM1595066
[840]
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[841]
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[842]
GSM1595069
[843]
GSM1595070
[844]
GSM1595071
[845]
GSM1595072
[846]
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[847]
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[848]
GSM1595075
[849]
GSM1595076
[850]
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[851]
GSM1595078
[852]
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[853]
GSM1595080
[854]
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[855]
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[856]
GSM1595083
[857]
GSM1595084
[858]
GSM1595085
[859]
GSM1595086
[860]
GSM1595087
[861]
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[862]
GSM1595089
[863]
GSM1595090
[864]
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[865]
GSM1595092
[866]
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[867]
GSM1595094
[868]
GSM1595095
[869]
GSM1595096
[870]
GSM1595097
[871]
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[872]
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[873]
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[874]
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[875]
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[876]
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[877]
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[878]
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[879]
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[880]
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[881]
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[882]
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[883]
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[884]
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[885]
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[886]
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[887]
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[888]
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[889]
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[890]
GSM1595117
[891]
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[892]
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[893]
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[894]
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[895]
GSM1595122
[896]
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[897]
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[898]
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[899]
GSM1595126
[900]
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[901]
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[902]
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[903]
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[904]
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[905]
GSM1595132
[906]
GSM1595133
[907]
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[908]
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[909]
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[910]
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[911]
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[912]
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[913]
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[914]
GSM1595141
[915]
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[916]
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[917]
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[918]
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[919]
GSM1595146
[920]
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[921]
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[922]
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[923]
GSM1595150
[924]
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[925]
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[926]
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[927]
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[928]
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[929]
GSM1595156
[930]
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[931]
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[932]
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[933]
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[934]
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[935]
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[936]
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[937]
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[938]
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[939]
GSM1595166
[940]
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[941]
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[942]
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[943]
GSM1595170
[944]
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[945]
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[946]
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[947]
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[948]
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[949]
GSM1595176
[950]
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[951]
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[952]
GSM1595179
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996
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10558
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Homo sapiens
title
Longitudinal transcriptional pediatric SLE study with clinical parameters
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2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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licence_read
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[3] object · 15 fields
id
data:geo:GSE72509
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72509
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null
bytes
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null
note
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
structure object · 15 fields
repository
GEO
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GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
access_statement_kind
data_availability_statement
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sample_count
117
group_sizes
null
group_sizes_basis
null
platform
16791
taxon
Homo sapiens
title
SLE lupus RNA-seq
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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false
licence_read
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gaps array · 6 items
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[3]
asset:data:geo:GSE65391 licence not read
[4]
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[5]
asset:data:geo:GSE72509 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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machine_learning
specific
support_vector_machine
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[0]
train_classifier
[1]
cross_validate
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roc_auc
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labelled_feature_matrix
evidence object · 3 fields
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quote
Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively.
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id
method-2
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differential_expression
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limma_voom
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Differential expression analysis
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[0]
normalise_counts
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differential_expression_fit
[2]
fdr_bh
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count_matrix_with_condition
evidence object · 3 fields
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0.7
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medium
quote
limma
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method-3
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machine_learning
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gradient_boosting
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Machine learning
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train_classifier
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cross_validate
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roc_auc
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labelled_feature_matrix
evidence object · 3 fields
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method-4
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network_analysis
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evidence object · 3 fields
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0.7
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PPI
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id
method-5
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diagnostic_evaluation
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label
Diagnostic test evaluation
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[0]
confusion_counts
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reference_standard_and_test
evidence object · 3 fields
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0.8
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high
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ROC curve
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[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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[0]
meta_analysis
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[8]
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candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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complete
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nothing:replicable_now
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train_classifier
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: support_vector_machine.
capability object · 4 fields
tier
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capability:computational_analysis
availability_state
owned
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
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accessions array · 3 items
[0]
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[1]
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GSE39088
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statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE65391, GSE72509, GSE39088 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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train_classifier
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MiniMax-M3.1-Flash
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minimax
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minimax
read_at
2026-11-01T17:44:12Z
independence
single_reader
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verbatim
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extraction
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paper
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GEO GSE39088
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PMID 35495164 full text
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GEO GSE39088
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agent:corpus-assay-engine
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ker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort. Our find
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Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35495164", "kind": "science-record", "revision": 5, "content_hash": "sha256:4e4548b0c60c493e699477d0ab0e893adda2eba27be5f0c39540c23209e05719", "created_at": "2026-11-01T18:14:22Z", "updated_at": "2026-11-01T22:48:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning.", "doi": "10.3389/fgene.2022.865559", "pmid": "35495164", "authors": ["Zhihang Jiang", "Mengting Shao", "Xinzhu Dai", "Zhixin Pan", "Dongmei Liu"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects several organs and causes variable clinical symptoms. Exploring new insights on genetic factors may help reveal SLE etiology and improve the survival of SLE patients. The current study is designed to identify key genes involved in SLE and develop potential diagnostic biomarkers for SLE in clinical practice. Expression data of all genes of SLE and control samples in GSE65391 and GSE72509 datasets were downloaded from the Gene Expression Omnibus (GEO) database. A total of 11 accurate differentially expressed genes (DEGs) were identified by the \"limma\" and \"RobustRankAggreg\" R package. All these genes were functionally associated with several immune-related biological processes and a single KEGG (Kyoto Encyclopedia of Genes and Genome) pathway of necroptosis. The PPI analysis showed that IFI44, IFI44L, EIF2AK2, IFIT3, IFITM3, ZBP1, TRIM22, PRIC285, XAF1, and PARP9 could interact with each other. In addition, the expression patterns of these DEGs were found to be consistent in GSE39088. Moreover, Receiver operating characteristic (ROC) curves analysis indicated that all these DEGs could serve as potential diagnostic biomarkers according to the area under the ROC curve (AUC) values. Furthermore, we constructed the transcription factor (TF)-diagnostic biomarker-microRNA (miRNA) network composed of 278 nodes and 405 edges, and a drug-diagnostic biomarker network consisting of 218 nodes and 459 edges. To investigate the relationship between diagnostic biomarkers and the immune system, we evaluated the immune infiltration landscape of SLE and control samples from GSE6539. Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort. Our findings may benefit the diagnosis of patients with SLE and guide in developing novel targeted therapy in treating SLE patients.", "claims": [{"id": "claim-method", "statement": "Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35495164", "locator": "sections[7] \"Machine Learning\" paragraph 2", "quote": "Machine learning methods, including LR, RF, XGBoost, SVM, and ANN (Li et al., 2021), were performed by the “glmnet”, “randomForest”, “xgboost”, “e1071”, and “neuralnet” R packages to develop classifiers for diagnostic classification, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35495164", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "IFI44 was identified as the optimal diagnostic biomarker for SLE and validated in an independent cohort, with an AUC of 0.850, diagnostic sensitivity of 0.923, and diagnostic specificity of 0.850.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35495164", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort."}, {"asset": "source:pmid:35495164", "locator": "sections[16] \"Identification of Optimal Biomarkers in SLE\" paragraph 5", "quote": "ROC curve analysis showed that AUC for IFI44 was 0.850 when distinguishing SLE patients from healthy controls, and the diagnostic sensitivity and specificity were 0.923 and 0.850, respectively (Figure 9C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "IFI44 was identified as the optimal diagnostic biomarker for SLE and validated in an independent cohort, with an AUC of 0.850, diagnostic sensitivity of 0.923, and diagnostic specificity of 0.850.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35495164"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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