Guo Wei, Shang Dong-Mei, Cao Jing-Hui, Feng Kaiyan, He Yi-Chun, Jiang Yang, Wang ShaoPeng, Gao Yu-Fei
Department of Outpatient, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Biomed Res Int. 2017;2017:6132436. doi: 10.1155/2017/6132436. Epub 2017 Feb 1.
As a pathological condition, epilepsy is caused by abnormal neuronal discharge in brain which will temporarily disrupt the cerebral functions. Epilepsy is a chronic disease which occurs in all ages and would seriously affect patients' personal lives. Thus, it is highly required to develop effective medicines or instruments to treat the disease. Identifying epilepsy-related genes is essential in order to understand and treat the disease because the corresponding proteins encoded by the epilepsy-related genes are candidates of the potential drug targets. In this study, a pioneering computational workflow was proposed to predict novel epilepsy-related genes using the random walk with restart (RWR) algorithm. As reported in the literature RWR algorithm often produces a number of false positive genes, and in this study a permutation test and functional association tests were implemented to filter the genes identified by RWR algorithm, which greatly reduce the number of suspected genes and result in only thirty-three novel epilepsy genes. Finally, these novel genes were analyzed based upon some recently published literatures. Our findings implicate that all novel genes were closely related to epilepsy. It is believed that the proposed workflow can also be applied to identify genes related to other diseases and deepen our understanding of the mechanisms of these diseases.
作为一种病理状况,癫痫是由大脑中异常的神经元放电引起的,这会暂时扰乱大脑功能。癫痫是一种发生于各年龄段的慢性疾病,会严重影响患者的个人生活。因此,迫切需要开发有效的药物或器械来治疗这种疾病。识别与癫痫相关的基因对于理解和治疗该疾病至关重要,因为由癫痫相关基因编码的相应蛋白质是潜在药物靶点的候选者。在本研究中,提出了一种开创性的计算工作流程,使用带重启的随机游走(RWR)算法来预测新的癫痫相关基因。如文献报道,RWR算法经常产生一些假阳性基因,在本研究中实施了置换检验和功能关联检验来筛选由RWR算法识别的基因,这大大减少了可疑基因的数量,最终仅得到33个新的癫痫基因。最后,基于一些最近发表的文献对这些新基因进行了分析。我们的研究结果表明,所有新基因都与癫痫密切相关。相信所提出的工作流程也可应用于识别与其他疾病相关的基因,并加深我们对这些疾病机制的理解。