Chen Lei, Yang Jing, Xing Zhihao, Yuan Fei, Shu Yang, Zhang YunHua, Kong XiangYin, Huang Tao, Li HaiPeng, Cai Yu-Dong
School of Life Sciences, Shanghai University, Shanghai, People's Republic of China.
College of Information Engineering, Shanghai Maritime University, Shanghai, People's Republic of China.
PLoS One. 2017 Apr 6;12(4):e0175185. doi: 10.1371/journal.pone.0175185. eCollection 2017.
Cancer is a significant public health problem worldwide. Complete identification of genes related to one type of cancer facilitates earlier diagnosis and effective treatments. In this study, two widely used algorithms, the random walk with restart algorithm and the shortest path algorithm, were adopted to construct two parameterized computational methods, namely, an RWR-based method and an SP-based method; based on these methods, an integrated method was constructed for identifying novel disease genes. To validate the utility of the integrated method, data for oral cancer were used, on which the RWR-based and SP-based methods were trained, thereby building two optimal methods. The integrated method combining these optimal methods was further adopted to identify the novel genes of oral cancer. As a result, 85 novel genes were inferred, among which eleven genes (e.g., MYD88, FGFR2, NF-κBIA) were identified by both the RWR-based and SP-based methods, 70 genes (e.g., BMP4, IFNG, KITLG) were discovered only by the RWR-based method and four genes (L1R1, MCM6, NOG and CXCR3) were predicted only by the SP-based method. Extensive analyses indicate that several novel genes have strong associations with cancers, indicating the effectiveness of the integrated method for identifying disease genes.
癌症是全球一个重大的公共卫生问题。全面鉴定与某一类型癌症相关的基因有助于早期诊断和有效治疗。在本研究中,采用了两种广泛使用的算法,即带重启的随机游走算法和最短路径算法,构建了两种参数化计算方法,即基于随机游走重启动算法(RWR)的方法和基于最短路径算法(SP)的方法;基于这些方法,构建了一种用于鉴定新型疾病基因的综合方法。为了验证该综合方法的效用,使用了口腔癌数据,在该数据上对基于RWR的方法和基于SP的方法进行训练,从而构建两种最优方法。进一步采用结合这些最优方法的综合方法来鉴定口腔癌的新型基因。结果,推断出85个新型基因,其中11个基因(如MYD88、FGFR2、NF-κBIA)通过基于RWR的方法和基于SP的方法均被鉴定出来,70个基因(如BMP4、IFNG、KITLG)仅通过基于RWR的方法被发现,4个基因(L1R1、MCM6、NOG和CXCR3)仅通过基于SP的方法被预测出来。广泛的分析表明,几个新型基因与癌症有很强的关联,这表明该综合方法在鉴定疾病基因方面是有效的。