Debnath Joy Prokash, Hossen Kabir, Sayed Sabrina Bintay, Khandaker Md Sayeam, Dev Preonath Chondrow, Sarker Saifuddin, Hossain Tanvir
Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
Child Health Research Foundation, Dhaka, 1207, Bangladesh.
Sci Rep. 2025 Jan 23;15(1):2922. doi: 10.1038/s41598-024-80519-7.
Monkeypox virus (MPXV), a zoonotic pathogen, re-emerged in 2022 with the Clade IIb variant, raising global health concerns due to its unprecedented spread in non-endemic regions. Recent studies have shown that Clade IIb (2022 MPXV) is marked by unique genomic mutations and epidemiological behaviors, suggesting variations in host-virus interactions. This study aimed to identify the differentially expressed genes (DEGs) induced by the 2022 MPXV infection through comprehensive bioinformatics analyses of microarray and RNA-Seq datasets from post-infected cell types with different MPXV clades. Subsequently, gene expression network analyses pinpoint the key DEGs, followed by their candidate drug assessment using the Drug SIGnatures DataBase (DSigDB) and validation by multiple machine learning algorithms. Comparative differential gene expression (DGE) analysis revealed 798 DEGs exclusive to the 2022 MPXV invasion in the skin cell types (keratinocytes). Intriguingly, 13 key DEGs were identified across hubs and clusters, highlighting their aberrant expressions in cell cycle regulation, immune responses, and cancer pathways. Biomarker screening via Random Forest (RF) model (selected with PyCaret from multiple models) and validation through t-distributed stochastic neighbor embedding (t-SNE) algorithm, principal component analysis (PCA), and ROC curve analysis employing Logistic Regression and Random Forest, identified 6 key DEGs (TXNRD1, CCNB1, BUB1, CDC20, BUB1B, and CCNA2) as promising biomarkers (AUC > 0.7) for clade IIb infection. This study anticipates that further investigation and clinical trials will catalyze novel detection and therapeutic options to combat 2022 MPXV infection in humans.
猴痘病毒（MPXV）是一种人畜共患病原体，于2022年携带IIb分支变体再次出现，因其在非流行地区前所未有的传播而引发全球健康担忧。最近的研究表明，IIb分支（2022年MPXV）具有独特的基因组突变和流行病学行为，表明宿主与病毒的相互作用存在差异。本研究旨在通过对来自不同MPXV分支感染后细胞类型的微阵列和RNA测序数据集进行全面的生物信息学分析，确定2022年MPXV感染诱导的差异表达基因（DEG）。随后，基因表达网络分析确定关键的DEG，接着使用药物特征数据库（DSigDB）对其候选药物进行评估，并通过多种机器学习算法进行验证。比较差异基因表达（DGE）分析揭示了在皮肤细胞类型（角质形成细胞）中2022年MPXV入侵所特有的798个DEG。有趣的是，在枢纽和聚类中确定了13个关键DEG，突出了它们在细胞周期调节、免疫反应和癌症途径中的异常表达。通过随机森林（RF）模型（从多个模型中用PyCaret选择）进行生物标志物筛选，并通过t分布随机邻域嵌入（t-SNE）算法、主成分分析（PCA）以及使用逻辑回归和随机森林的ROC曲线分析进行验证，确定了6个关键DEG（TXNRD1、CCNB1、BUB1、CDC20、BUB1B和CCNA2）作为IIb分支感染有前景的生物标志物（AUC > 0.7）。本研究预计，进一步的研究和临床试验将催生出对抗人类2022年MPXV感染的新型检测和治疗方案。
