Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types.
Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types.
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DOI：
10.1101/gr.275723.121
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发表时间：
2022-03
期刊：
影响因子：
7
通讯作者：
Weng Z
中科院分区：
文献类型：
--
作者：
Moore JE;Zhang XO;Elhajjajy SI;Fan K;Pratt HE;Reese F;Mortazavi A;Weng Z
准确的转录起始点(TSS)注释对于理解转录调控及其在人类疾病中的作用至关重要。像GENCODE这样的基因集合包含数以万计的SSs的注释，但并不是所有这些注释都经过实验验证，也不包含关于细胞类型特定用途的信息。因此，我们试图通过整合来自115个细胞和组织类型的基因表达分析(RAMPAGE)数据的RNA注释和启动子图谱来生成实验验证的TSS集合，这导致了大约5万个具有代表性的RAMPAGE峰的集合。这些峰主要位于GENCODE注释的TSS的近端，并与其他转录分析一致。因为RAMPAGE使用成对的末端阅读，所以我们能够通过分析阅读伙伴的3‘端的基因组位置来将峰与转录本联系起来。使用这种配对末端信息，我们将绝大多数(3.7万)狂暴峰归类为已验证的TSS，更新了20%的GENCODE基因的TSS注释。我们还发现，这些更新的TSS注释得到了表观基因组和其他转录数据集的支持。为了显示这个疯狂的rPeak收集的实用性，我们将其与NHGRI/EBI基因组范围关联研究(GWAS)目录交叉，并确定了新的候选GWAS基因。总体而言，我们的工作表明了整合实验数据以进一步完善TSS注释的重要性，并为生物界提供了宝贵的资源。
Accurate transcription start site (TSS) annotations are essential for understanding transcriptional regulation and its role in human disease. Gene collections such as GENCODE contain annotations for tens of thousands of TSSs, but not all of these annotations are experimentally validated nor do they contain information on cell type–specific usage. Therefore, we sought to generate a collection of experimentally validated TSSs by integrating RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression (RAMPAGE) data from 115 cell and tissue types, which resulted in a collection of approximately 50 thousand representative RAMPAGE peaks. These peaks are primarily proximal to GENCODE-annotated TSSs and are concordant with other transcription assays. Because RAMPAGE uses paired-end reads, we were then able to connect peaks to transcripts by analyzing the genomic positions of the 3′ ends of read mates. Using this paired-end information, we classified the vast majority (37 thousand) of our RAMPAGE peaks as verified TSSs, updating TSS annotations for 20% of GENCODE genes. We also found that these updated TSS annotations are supported by epigenomic and other transcriptomic data sets. To show the utility of this RAMPAGE rPeak collection, we intersected it with the NHGRI/EBI genome-wide association study (GWAS) catalog and identified new candidate GWAS genes. Overall, our work shows the importance of integrating experimental data to further refine TSS annotations and provides a valuable resource for the biological community.
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DOI：
10.1126/science.aah7111
发表时间：
2017-01-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Liu SJ;Horlbeck MA;Cho SW;Birk HS;Malatesta M;He D;Attenello FJ;Villalta JE;Cho MY;Chen Y;Mandegar MA;Olvera MP;Gilbert LA;Conklin BR;Chang HY;Weissman JS;Lim DA
通讯作者：
Lim DA
长链非编码 RNA 在癌症中的作用、功能和机制。
DOI：
10.1016/j.gpb.2015.09.006
发表时间：
2016-02
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
Fang Y;Fullwood MJ
通讯作者：
Fullwood MJ
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
56.9
作者：
Rajarajan, Prashanth;Borrman, Tyler;Akbarian, Schahram
通讯作者：
Akbarian, Schahram
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P