Kartchner David, McCoy Kevin, Dubey Janhvi, Zhang Dongyu, Zheng Kevin, Umrani Rushda, Kim James J, Mitchell Cassie S
Laboratory for Pathology Dynamics, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Biology (Basel). 2023 Sep 21;12(9):1269. doi: 10.3390/biology12091269.
Multiple studies have reported new or exacerbated persistent or resistant hypertension in patients previously infected with COVID-19. We used literature-based discovery to identify and prioritize multi-scalar explanatory biology that relates resistant hypertension to COVID-19. Cross-domain text mining of 33+ million PubMed articles within a comprehensive knowledge graph was performed using SemNet 2.0. Unsupervised rank aggregation determined which concepts were most relevant utilizing the normalized HeteSim score. A series of simulations identified concepts directly related to COVID-19 and resistant hypertension or connected via one of three renin-angiotensin-aldosterone system hub nodes (mineralocorticoid receptor, epithelial sodium channel, angiotensin I receptor). The top-ranking concepts relating COVID-19 to resistant hypertension included: cGMP-dependent protein kinase II, MAP3K1, haspin, ral guanine nucleotide exchange factor, N-(3-Oxododecanoyl)-L-homoserine lactone, aspartic endopeptidases, metabotropic glutamate receptors, choline-phosphate cytidylyltransferase, protein tyrosine phosphatase, tat genes, MAP3K10, uridine kinase, dicer enzyme, CMD1B, USP17L2, FLNA, exportin 5, somatotropin releasing hormone, beta-melanocyte stimulating hormone, pegylated leptin, beta-lipoprotein, corticotropin, growth hormone-releasing peptide 2, pro-opiomelanocortin, alpha-melanocyte stimulating hormone, prolactin, thyroid hormone, poly-beta-hydroxybutyrate depolymerase, CR 1392, BCR-ABL fusion gene, high density lipoprotein sphingomyelin, pregnancy-associated murine protein 1, recQ4 helicase, immunoglobulin heavy chain variable domain, aglycotransferrin, host cell factor C1, ATP6V0D1, imipramine demethylase, TRIM40, H3C2 gene, COL1A1+COL1A2 gene, QARS gene, VPS54, TPM2, MPST, EXOSC2, ribosomal protein S10, TAP-144, gonadotropins, human gonadotropin releasing hormone 1, beta-lipotropin, octreotide, salmon calcitonin, des-n-octanoyl ghrelin, liraglutide, gastrins. Concepts were mapped to six physiological themes: altered endocrine function, 23.1%; inflammation or cytokine storm, 21.3%; lipid metabolism and atherosclerosis, 17.6%; sympathetic input to blood pressure regulation, 16.7%; altered entry of COVID-19 virus, 14.8%; and unknown, 6.5%.
多项研究报告称，先前感染过新冠病毒的患者出现了新的或加重的持续性或难治性高血压。我们利用基于文献的发现方法来识别和优先考虑将难治性高血压与新冠病毒相关联的多尺度解释生物学。使用SemNet 2.0在一个综合知识图谱中对3300多万篇PubMed文章进行跨领域文本挖掘。无监督排名聚合利用归一化的HeteSim分数确定哪些概念最相关。一系列模拟确定了与新冠病毒和难治性高血压直接相关或通过肾素-血管紧张素-醛固酮系统的三个枢纽节点（盐皮质激素受体、上皮钠通道、血管紧张素I受体）之一相连的概念。将新冠病毒与难治性高血压相关的排名靠前的概念包括：环磷酸鸟苷依赖性蛋白激酶II、丝裂原活化蛋白激酶激酶激酶1、哈斯本蛋白、ral鸟嘌呤核苷酸交换因子、N-（3-氧代十二烷酰基）-L-高丝氨酸内酯、天冬氨酸内肽酶、代谢型谷氨酸受体、胆碱磷酸胞苷转移酶、蛋白酪氨酸磷酸酶、tat基因、丝裂原活化蛋白激酶激酶10、尿苷激酶、切酶、CMD1B、USP17L2、细丝蛋白A、输出蛋白5、生长激素释放激素、β-促黑素细胞激素、聚乙二醇化瘦素、β-脂蛋白、促肾上腺皮质激素、生长激素释放肽2、阿片促黑激素皮质素原、α-促黑素细胞激素、催乳素、甲状腺激素、聚-β-羟基丁酸解聚酶、CR 1392、BCR-ABL融合基因、高密度脂蛋白鞘磷脂蛋白、妊娠相关小鼠蛋白1、recQ4解旋酶、免疫球蛋白重链可变区、去糖基转铁蛋白、宿主细胞因子C1、ATP6V0D1、丙咪嗪脱甲基酶、TRIM40、H3C2基因、COL1A1+COL1A2基因、QARS基因、VPS54、TPM2、MPST、EXOSC2、核糖体蛋白S10、TAP-144、促性腺激素、人促性腺激素释放激素1、β-促脂解素、奥曲肽、鲑鱼降钙素、去n-辛酰基胃泌素、利拉鲁肽、胃泌素。这些概念被映射到六个生理主题：内分泌功能改变，23.1%；炎症或细胞因子风暴，21.3%；脂质代谢和动脉粥样硬化，17.6%；交感神经对血压调节的输入，16.7%；新冠病毒进入改变，14.8%；未知，6.5%。
