摘要
可变剪接是一种广泛存在于生物体中造成蛋白质多样性的重要机制,它对细胞的增殖、分化、发育、凋亡等一系列重要的生物过程具有重要精细调控的作用。近年来,人们发现多种复杂疾病的产生往往伴随着剪接异构体的紊乱表达。为了研究剪接异构体在整体分布上的差异,该文提出一种基于中值的JS散度可变剪接(AS)差异分析方法。结果表明,该文的方法能够发现大量在剪接异构体整体分布上具有显著差异的基因。这些基因不仅富集在一些癌症密切相关的通路,而且也富集在一些基于可变剪接调控的信号通路、细胞分裂过程和蛋白质功能等通路。此外,与基因层次的差异分析相比,可变剪接显著差异的基因在生存分析方面也具有更好的性能。总之,该文提出基于中值的JS散度可变剪接差异分析方法,将为进一步揭示可变剪接在癌症中的机制奠定基础。
Alternative splicing is an important mechanism of protein diversity in a wide range of organisms,which plays an important role in the fine regulation of cell proliferation,differentiation,development,apoptosis and a series of important biological processes.In recent years,it is found that the occurrence of multiple complex diseases is often accompanied by the disordered expression of splicing isoforms.In order to study the difference of splicing isoforms on the whole distribution,a differential analysis method of Alternative Splicing(AS)based on the median value by Jensen-Shannon(JS)divergence is proposed in this paper.The results show the method can finds plenty of genes with significant differences in the overall distribution of splicing isoforms.These genes are not only concentrated in some cancer related pathways,but also in some signaling pathways based on alternative splicing regulation,cell division process and protein function.In addition,compared with the gene-level differential analysis,the genes with significant difference in alternative splicing also have better performance in survival analysis.In conclusion,the proposed method will lay a foundation for further revealing the mechanism of alternative splicing in cancer.
作者
刘文斌
王兵
方刚
石晓龙
许鹏
LIU Wenbin;WANG Bing;FANG Gang;SHI Xiaolong;XU Peng(College of Computer Science and Artificial Intelligence,Wenzhou University,Wenzhou 325035,China;Institute of Computing Science and Technology,Guangzhou University,Guangzhou 510006,China;School of Computer Science and Information Technology,Qiannan Normal University for Nationalities,Duyun 558000,China)
出处
《电子与信息学报》
EI
CSCD
北大核心
2020年第6期1392-1400,共9页
Journal of Electronics & Information Technology
基金
国家重点研发计划(2019YFA0706402)
国家自然科学基金(61572367,61573017,61972107,61972109)。
关键词
可变剪接
癌症
JS散度
KEGG通路
驱动基因
Alternative splicing
Cancer
Jensen-Shannon(JS)divergence
Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway
Driver gene
