基于Jensen-Shannon差异的可变剪接分析.pdfVIP

第 30 卷第 4 期 2012 年 12 月 江苏师范大学学报(自然科学版) Journal of Jiangsu Normal University(Natural Science Edition) Vol. 30.No. 4 Dec. .2012 基于 Jensen-Shannon 差异的可变剪接分析 孙磊，徐钊 (中国矿业大学信息与电气工程学院，江苏徐州 221008) 摘要:针对传统方法仅能分析基因的单→可变剪接模式的问题，设计了一种基于 Jensen-Shannon(JS)差异的生物 信息学方法 ASAT.用以分析基因在转录本水平的多可变剪接模式.将 ASAT 应用于小鼠转录因子 Klfl 敲除实验 的 RNA-Seq 数据，预测出 12 个发生了可变剪接变化的基因，并在转录本水平对这些基因的可变剪接模式进行了 分析.通过基因功能富集分析，发现其中有两个基因 Timp1 、 Gm13654 与 Klf1 能够显著富集在红血球发育、分化及 动态平衡的生物过程.结果表明.ASAT 可预测到与生物功能相关的可变剪接基因，并能够分析转录本水平的可变 剪接模式. 关键词:可变剪接; J ensen-Shannon 差异 ;RNA-Seq;基因功能富集分析 中图分类号: Q7 .Q81, TP391 文献标识码 :A 文章编号: 2095-4298(2012)04-0061-06 Alternative splicing analysis based on J ensen-Shannon divergence Sun Lei. Xu Zhao (School of Information Electrical Engineering ,China University of Mining Technology.Xuzhou 221008.Jiangsu.China) Abstract: Due to the fact that traditional methods can only analyze single alternative splicing (AS) pattern of a gene. a bioinformatics method-alternative splicing analysis at transcript level (ASAT) is designed for analyzing multi-AS patterns of a gene at the transcript level. By applying ASAT to an RNA-Seq dataset on the mouse transcription fac- tor Klfl knockout experiment. 12 genes with significant AS changes are predicted. and then the AS analysis is con ducted at the transcript level for the genes detected. By gene ontology (GO) analysis. it is found that two genes we predicted. namely Tim1 and Gm13654. together with Klf1. significantly enrich in the biological processes of eryth- rocyte development. differentiation and homeostasis. The result indicates that ASAT can predict AS genes relevant to biological functions and analyze AS patterns at the transcript level. Key words: alternative splicing; J ensen-Shannon divergence; RNA-Seq; gene ontology( GO) analysis 。 引言 剪接(splicing)指的是前体 RNA 的内含子去除、外显子接合的过程，它是成熟 RNA 形成的重要机制. 可变剪接 (alternative splicing. AS.也叫选择性剪接)是指相对于基因主要剪接模式之外的其他剪接模式.不 同的可变剪接模式能够产生不同的 RNA. 它是蛋白质多样性的根本原因[1-4J ? Mortazavi 等通过对小鼠的 脑、肝脏和骨髓肌的转录组进行测序发现，其