Department of Biomedical Informatics, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of the Ministry of Education, Center for Non-Coding RNA Medicine, Peking University Health Science Center Beijing, Beijing, China.
BMC Bioinformatics. 2021 Dec 11;22(1):587. doi: 10.1186/s12859-021-04513-w.
The arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50-60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein-protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.
动脉动脉瘤是指血管壁的局部扩张，在普通人群中很常见。大多数动脉瘤病例在突然破裂之前通常没有症状，而破裂通常是致命的，死亡率极高（约 50-60%）。因此，迫切需要对动脉瘤进行早期诊断、预防和管理。不幸的是，目前对各种动脉瘤亚型的疾病驱动基因的理解仍然有限，而且由于没有适当的生物标志物和药物靶点，因此没有专门针对动脉瘤治疗的药物。在这项研究中，根据蛋白质-蛋白质相互作用网络分析了动脉瘤亚型，以更好地了解动脉瘤的发病机制。通过测量动脉瘤亚型的基于网络的接近度，我们确定了主动脉瘤和主动脉夹层之间存在相关的最接近关系。然后，对每种动脉瘤亚型的候选驱动基因进行了改进的随机游走方法优先级排序。此后，收集了 6 个人类动脉瘤亚型的转录组，并鉴定了差异表达基因，以进一步筛选潜在的驱动基因。上述驱动基因的功能富集表明泛素化和程序性细胞死亡在动脉瘤发病机制中具有一般作用。特别是，我们在相应的转录组中进一步观察到 BCL-2 介导的细胞凋亡途径和半胱天冬酶-1 相关细胞焦亡在脑动脉瘤和颅内动脉瘤性蛛网膜下腔出血的发展中的参与。
