Computational Resources for the Compilation and Distribution of Transcription Fac

用于转录因子编译和分发的计算资源

• 批准号: 8247660
• 负责人: WYETH W WASSERMAN
• 金额: $ 33.25万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247660
• 关键词: Binding; Bioinformatics; Biology; Biomedical Research; Cataloging; Catalogs; Cells; Chemicals; Collection; Communities; Complex; Computational algorithm; Computer software; Controlled Vocabulary; Coupled; Coupling; DNA Sequence; DNA analysis; DNA-Binding Proteins; Data; Data Set; Databases; Deposition; Development; Environment; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genome; Genomics; Health; Individual; Laboratories; Laboratory Research; Link; Malignant Neoplasms; Modeling; Molecular; Neoplasm Metastasis; Nuclear Proteins; Procedures; Proteins; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Scientist; Series; Services; Signal Transduction; Source; Stem cells; System; Tissues; Transcriptional Regulation; Vocabulary; Work; base; cancer cell; cell type; computer studies; computing resources; data exchange; data modeling; design; genome sequencing; improved; interest; meetings; open source; programs; public health relevance; repository; research and development; research study; response; software systems; success; transcription factor; virtual

DESCRIPTION (provided by applicant): A primary focus of genome biology is the study of gene regulation. Complex regulatory programs give rise to diverse tissues and cell types, and allow cells to respond to ever-changing molecular signals in their environments. The development of tissues from stem cells, the metastasis of cancer cells and the response of cells to chemicals in the environment, are all directly tied to gene regulation. Gene regulation is performed in part by nuclear proteins called transcription factors, many of which recognize specific DNA sequences within and surrounding genes. The DNA sequences bound by the transcription factors can be determined by high- throughput lab procedures. In addition to the experimental studies, computational algorithms are improving for the prediction of target sequences bound by these key proteins. Unfortunately, the results from such experimental and computational studies are dispersed in a haphazard manner, often with static annotations to expired versions of genome sequence assemblies. The lack of organized information about DNA binding proteins slows research, decreasing the value of the exceptional research being performed in laboratories around the globe. An organized data repository coupled to software for gene analysis will enhance the success of studies across diverse fields of biomedical research. This proposal outlines the development of the PAZAR open-access repository for regulatory sequence and transcription factor annotation, as well as the development of accompanying computational services for the applied study of regulatory sequences. PAZAR, modeled on an analogy to a shopping mall, allows an individual or research team to share their data through a virtual boutique. These boutiques are managed independently but use a common infrastructure. The underlying data model is intended to enable experts to organize and share the gene regulation data generated in their research studies while keeping it up-to-date with the current reference genome. This proposal outlines a series of extensions to the base system, allowing PAZAR to serve as the central open-source and open-access resource for investigators interested in gene regulation. The key objectives are: 7 Expansion and extension of PAZAR software: Incorporate controlled vocabularies and transcription factor referencing catalogs, improve data submission procedures and expand middle-layer software for the handling of additional data classes 7 Analysis software coupling to PAZAR: Link existing bioinformatics software to PAZAR for dynamic analyses of gene regulation 7 Transcription Factor encyclopedia (TFe): Continue development of the TFe collection of articles about transcription factors, which serves as a key means of recruiting expert laboratories to deposit data into PAZAR PUBLIC HEALTH RELEVANCE: The proposed work will provide the scientific community with an open-access and open-source resource for the dissemination and analysis of DNA regulatory sequence data. This bioinformatics resource is critically important for understanding when and where genes will be active in the body, a key problem in modern health research studies ranging from stem cells to cancer. The PAZAR system captures and organizes data from laboratory research on transcription regulation, facilitating studies of gene regulation and genetic networks.

描述(申请人提供)：基因组生物学的一个主要焦点是研究基因调控。复杂的调控程序产生了不同的组织和细胞类型，并允许细胞对环境中不断变化的分子信号做出反应。干细胞组织的发育、癌细胞的转移以及细胞对环境中化学物质的反应，都与基因调控直接相关。基因调控在一定程度上是由被称为转录因子的核蛋白执行的，其中许多转录因子识别基因内部和周围的特定DNA序列。转录因子结合的DNA序列可以通过高通量的实验室程序来确定。除了实验研究外，计算机算法正在改进，以预测这些关键蛋白质结合的目标序列。不幸的是，这种实验和计算研究的结果是以一种随意的方式散布的，通常带有对基因组序列组装的过期版本的静态注释。缺乏关于DNA结合蛋白的有组织的信息减缓了研究，降低了全球实验室正在进行的特殊研究的价值。一个有组织的数据库与基因分析软件相结合，将提高生物医学研究不同领域的研究的成功。该提案概述了用于调控序列和转录因子注释的Pazar开放获取储存库的开发，以及用于调控序列应用研究的伴随计算服务的开发。Pazar模仿购物中心，允许个人或研究团队通过虚拟精品店分享他们的数据。这些精品店是独立管理的，但使用共同的基础设施。基础数据模型旨在使专家能够组织和共享在其研究中产生的基因调控数据，同时使其与当前的参考基因组保持最新。该提案概述了对基本系统的一系列扩展，允许Pazar作为对基因调控感兴趣的研究人员的中央开源和开放获取资源。Pazar软件的主要目标是：7扩展和扩展Pazar软件：纳入受控词汇和转录因子参考目录，改进数据提交程序，并扩展处理额外数据类别的中间层软件7与Pazar耦合的分析软件：将现有的生物信息学软件连接到Pazar以进行基因调控的动态分析7转录因子百科全书(TFE)：继续开发关于转录因子的TFE文章集，作为招募专家实验室将数据存入Pazar的关键手段 公共卫生相关性：拟议的工作将为科学界提供一个开放获取和开放源码的资源，用于传播和分析DNA调控序列数据。这种生物信息学资源对于了解基因何时何地在体内活跃至关重要，这是从干细胞到癌症等现代健康研究中的一个关键问题。Pazar系统捕获和组织来自转录调控实验室研究的数据，促进基因调控和遗传网络的研究。

项目成果

On the identification of potential regulatory variants within genome wide association candidate SNP sets.

• DOI: 10.1186/1755-8794-7-34
• 发表时间: 2014-06-11
• 期刊: BMC medical genomics
• 影响因子: 2.7
• 作者: Chen CY;Chang IS;Hsiung CA;Wasserman WW
• 通讯作者: Wasserman WW

JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles.

• DOI: 10.1093/nar/gkt997
• 发表时间: 2014-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Mathelier A;Zhao X;Zhang AW;Parcy F;Worsley-Hunt R;Arenillas DJ;Buchman S;Chen CY;Chou A;Ienasescu H;Lim J;Shyr C;Tan G;Zhou M;Lenhard B;Sandelin A;Wasserman WW
• 通讯作者: Wasserman WW

Compensating for literature annotation bias when predicting novel drug-disease relationships through Medical Subject Heading Over-representation Profile (MeSHOP) similarity.

• DOI: 10.1186/1755-8794-6-s2-s3
• 发表时间: 2013
• 期刊: BMC medical genomics
• 影响因子: 2.7
• 作者: Cheung WA;Ouellette BF;Wasserman WW
• 通讯作者: Wasserman WW

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

• DOI: 10.1038/nature10933
• 发表时间: 2012-04-04
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Shah, Sohrab P.;Roth, Andrew;Goya, Rodrigo;Oloumi, Arusha;Ha, Gavin;Zhao, Yongjun;Turashvili, Gulisa;Ding, Jiarui;Tse, Kane;Haffari, Gholamreza;Bashashati, Ali;Prentice, Leah M.;Khattra, Jaswinder;Burleigh, Angela;Yap, Damian;Bernard, Virginie;McPherson, Andrew;Shumansky, Karey;Crisan, Anamaria;Giuliany, Ryan;Heravi-Moussavi, Alireza;Rosner, Jamie;Lai, Daniel;Birol, Inanc;Varhol, Richard;Tam, Angela;Dhalla, Noreen;Zeng, Thomas;Ma, Kevin;Chan, Simon K.;Griffith, Malachi;Moradian, Annie;Cheng, S. -W. Grace;Morin, Gregg B.;Watson, Peter;Gelmon, Karen;Chia, Stephen;Chin, Suet-Feung;Curtis, Christina;Rueda, Oscar M.;Pharoah, Paul D.;Damaraju, Sambasivarao;Mackey, John;Hoon, Kelly;Harkins, Timothy;Tadigotla, Vasisht;Sigaroudinia, Mahvash;Gascard, Philippe;Tlsty, Thea;Costello, Joseph F.;Meyer, Irmtraud M.;Eaves, Connie J.;Wasserman, Wyeth W.;Jones, Steven;Huntsman, David;Hirst, Martin;Caldas, Carlos;Marra, Marco A.;Aparicio, Samuel
• 通讯作者: Aparicio, Samuel

Quantitative biomedical annotation using medical subject heading over-representation profiles (MeSHOPs).

• DOI: 10.1186/1471-2105-13-249
• 发表时间: 2012-09-27
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Cheung WA;Ouellette BF;Wasserman WW
• 通讯作者: Wasserman WW