基于基因集富集分析的畜禽复杂性状GWAS分析平台及其应用课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,基于基因集富集分析的畜禽复杂性状GWAS分析平台及其应用,潘玉春 王起山,panyc,2011.8.12,基于基因集富集分析的畜禽复杂性状GWAS分析平台及其应用潘玉,一、背景,1,一、背景1,GWAS,全基因组关联分析方法（,GWAS,）是近几年提出的复杂性状功能基因鉴定的新策略。该方法是基于全基因组范围内的序列变异，筛选出那些与性状关联的,SNPs,。,问题,需要对数以万计的,SNP,位点进行检测，可能出现许多假阳性或假阴性的结果。,缺乏对显著,SNP,的生物学解释（如所处的代谢通路、生物过程等），导致很难解释性状的分子遗传机制。,2,GWAS2,GSEA-GWAS,基因集富集分析的基本思想是使用预定义的基因集（通常来自功能注释或先前实验的结果），筛选出与性状显著相关的通路等注释集合。,引入基因集富集分析的方法比单基因分析能获得更多、更有生物学意义的基因信息，将有助于解决上述两个问题。,Mootha 等（2003）提出用于表达芯片的数据分析,Wang Kai 等（2007）扩展到GSEA-GWAS,3,GSEA-GWAS 3,GWAS using single marker based association test,4,GWAS using single marker based,GWAS,分析结果,选择,GWAS,结果显著的,SNP,集合进行,Fisher,检验,显著的基因集,基因集,QTL,映射,功能验证,GSEA-GWAS,分析流程,基因映射,SNP,基因集映射基因,基因集定义,选择,GWAS,结果中所有,SNP,进行富集分析,5,GWAS分析结果选择GWAS结果显著的SNP 集合进行Fis,目前基于基因集富集分析的全基因组关联分析方法（GSEA-GWAS）已经应用于人类（随机无关人群或核心家系）和小鼠（高度近交）的资源群体。,www.nr.no/pages/gseasnp,(Bioinformatics 2008),https:/webtools.imbs.uni-luebeck.de/snptogo,(Bioinformatics 2008),GSEA-GWAS,研究进展,6,目前基于基因集富集分析的全基因组关联分析方法（GSEA-GW,二、畜禽,GSEA-GWAS,平台,牛基因组SNP功能注释与Fisher富集分析平台,Pathway:,转录调控、信号转导、代谢,Gene Ontology:,cellular component,biological process,molecular function,支持基因集,牛,SNP,功能注释及,Fisher,富集分析平台,8,KEGG Pathway:支持基因集牛SNP功能注释及Fi,Homepage of SNPpath,Cluster for Computering,SNPpath,Web Server,Path details,Result Page,Gene Ontology associated with traits,MySQL Database,Gene Ontology,分析流程,9,Homepage of SNPpathCluster for,Fishers,精确概率法利用超几何分布的原理推断每个基因集中的差异表达基因的比例是否与整个基因芯片上差异表达基因的比例相同。,分析原理,10,Fishers精确概率法利用超几何分布的原理推断每个基因,11,分析实例,Snelling et al.2010 Journal of Animal Science,2013,animals,BovineSNP50 BeadChip(50K)assay,birth weight(BWT),BW gain from birth to weaning,adjusted to 205 days(WG),205-day adjusted weaning weight(WW),160-day adjusted postweaning BW gain(PWG),365-day adjusted yearling weight(YW).,11,11分析实例Snelling et al.2010 Jou,12,12,13,13,发表论文,14,发表论文14,KEGG Pathway:,转录调控、信号转导、代谢,Gene Ontology:,cellular component,biological process,molecular function,the Pfam protein families database(Pfam),protein domains,families and functional sites(PROSITE),猪、牛、鸡基因集富集分析平台,支持基因集,15,KEGG Pathway:猪、牛、鸡基因集富集分析平台支持,Single column,P-,values,the data can be analyzed using Irizarrys method；,Two columns of,P-,values,the data can be analyzed using either the F,test,or t,test,;,The program also accepts up to 5000 columns of P-values which can be analyzed using either the Efrons re-standardized.,支持物种,猪、牛、鸡,分析方法,16,Single column P-values,the da,程序主页,17,程序主页17,注释集合,18,注释集合18,富集分析流程,19,富集分析流程19,Snelling et al.2010.,J.Anim.Sci.88(3):837848.,To illustrate the application of GWASknow,we analyzed the SNP data from the GWAS of growth in crossbred beef cattle which used,BovineSNP50 BeadChip(50K)assay,.Body weights(BW)gain from birth to weaning were utilized,.,分析实例,20,Snelling et al.2010.J.Anim.,The analysis results by the restandardized method are shown.A total of 28 KEGG pathway gene sets having,FDR-corrected p-values 0.01,were tabulated.,21,The analysis results by the re,animalgenome.org/cgi-bin/QTLdb/BT/summary,Many of the gene sets we identified made good biological senses.For example,The KEGG terms,Selenoamino acid metabolism,and,O-Glycan biosynthesis,overlap QTL described for average daily gain,body weight,feed conversion ratio.,QTL,映射,22,animalgenome.org/cgi-bi,相关论文,23,相关论文23,Thanks!,农业与生物学院动物科学系,上海市兽医生物技术重点实验室,24,Thanks!农业与生物学院动物科学系24,