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Identification of the immune-related biomarkers in Behcet’s disease by plasma proteomic analysis

免疫系统 接收机工作特性 医学 免疫学 计算生物学 肿瘤科 内科学 生物 生物信息学
作者
Huan Liu,Panpan Zhang,Fuzhen Li,Xiao Xiao,Yinan Zhang,Na Li,Liping Du,Peizeng Yang
出处
期刊:Arthritis Research & Therapy [Springer Nature]
卷期号:25 (1) 被引量:5
标识
DOI:10.1186/s13075-023-03074-y
摘要

Abstract Background This study aimed to investigate the expression profile of immune response-related proteins of Behcet’s disease (BD) patients and identify potential biomarkers for this disease. Methods Plasma was collected from BD patients and healthy controls (HC). Immune response-related proteins were measured using the Olink Immune Response Panel. Differentially expressed proteins (DEPs) were used to construct prediction models via five machine learning algorithms: naive Bayes, support vector machine, extreme gradient boosting, random forest, and neural network. The prediction performance of the five models was assessed using the area under the curve (AUC) value, recall (sensitivity), specificity, precision, accuracy, F1 score, and residual distribution. Subtype analysis of BD was performed using the consensus clustering method. Results Proteomics results showed 43 DEPs between BD patients and HC ( P < 0.05). These DEPs were mainly involved in the Toll-like receptor 9 and NF-κB signaling pathways. Five models were constructed using DEPs [interleukin 10 (IL10), Fc receptor like 3 (FCRL3), Mannan-binding lectin serine peptidase 1 (MASP1), NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2), FAM3 metabolism regulating signaling molecule B (FAM3B), and O-6-methylguanine-DNA methyltransferase (MGMT)]. Among these models, the neural network model showed the best performance (AUC = 0.856, recall: 0.692, specificity: 0.857, precision: 0.900, accuracy: 0.750, F1 score: 0.783). BD patients were divided into two subtypes according to the consensus clustering method: one with high disease activity in association with higher expression of tripartite motif-containing 5 (TRIM5), SH2 domain-containing 1A (SH2D1A), phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), hematopoietic cell-specific Lyn substrate 1 (HCLS1), and DNA fragmentation factor subunit alpha (DFFA) and the other with low disease activity in association with higher expression of C–C motif chemokine ligand 11 (CCL11). Conclusions Our study not only revealed a distinctive immune response-related protein profile for BD but also showed that IL10, FCRL3, MASP1, NF2, FAM3B, and MGMT could serve as potential immune biomarkers for this disease. Additionally, a novel molecular disease classification model was constructed to identify subsets of BD.
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