Systematic analysis of gene regulatory networks

基因调控网络的系统分析

• 批准号: 7732273
• 负责人: Minoru S Ko
• 金额: $ 34.54万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732273
• 关键词: Aging; Algorithms; Behavior; Binding Sites; Cell Line; Cells; Classification; Complex; Computer software; Condition; Data Analyses; Databases; Embryo; Expressed Sequence Tags; Gene Expression; Gene Targeting; Genes; Glass; Goals; In Situ; Internet; Maintenance; Monitor; Mus; Numbers; Oligonucleotide Probes; Online Systems; Organ; Pattern; Pilot Projects; Process; Protein Overexpression; Regulator Genes; Replacement Therapy; Research Project Grants; Resources; Slide; Stem cells; Structure; Transcript; Work; cDNA Library; embryonic stem cell; mouse genome; pluripotency; self-renewal; tool; transcription factor; user-friendly

We have been developing tools and resources that make it possible to analyze a large number of genes in various experimental conditions. In our earlier work, we 1) constructed cDNA libraries from early mouse embryos and stem cells and generated a large number of expressed sequence tags (ESTs), 2) developed a glass-slide microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 44,000 unique mouse transcripts, 3) produced web-based ANOVA-FDR software to provide user-friendly microarray data analysis, and 4) developed an algorithm and a fully-automated computational pipeline for transcript assembly from expressed sequences aligned to the mouse genome. In addition, we recently developed a comprehensive database and web browser of the binding sites of transcription factors (TFs) and cis-regulatory modules (CRMs) on the mouse genome. These resources and tools are now applied to the systematic analysis of gene regulatory networks in mouse embryonic stem cells. In our pilot project, we have demonstrated that it is possible to analyze and identify downstream target genes by monitoring the global gene expression patterns of mouse ES cell lines, when a gene encoding a specific TF (Pou5f1 or Oct34 or Oct4 in this case) is manipulated so that the gene can be overexpressed or repressed. We are now extending this strategy to many transcription factors. In particular, during the last year, we have extended this strategy to other key transcription factors (Sox2 and Nanog) in mouse ES cells.

我们一直在开发工具和资源，使其能够在各种实验条件下分析大量基因。在我们早期的工作中，我们1）从早期小鼠胚胎和干细胞构建cDNA文库并产生大量表达序列标签（EST），2）开发了一个载玻片微阵列平台，该平台含有原位合成的60-mer寡核苷酸探针，代表了大约44，000个独特的小鼠转录本，3）制作了基于网络的ANOVA-FDR软件以提供用户友好的微阵列数据分析，和4）开发了一种算法和全自动计算管道，用于从与小鼠基因组比对的表达序列组装转录物。此外，我们最近开发了一个全面的数据库和网络浏览器的结合位点的转录因子（TF）和顺式调控模块（CRM）的小鼠基因组。这些资源和工具现在被应用于小鼠胚胎干细胞基因调控网络的系统分析。在我们的试点项目中，我们已经证明，通过监测小鼠ES细胞系的全局基因表达模式，当操纵编码特定TF的基因（在这种情况下为Pou 5 f1或Oct 34或Oct 4）时，可以分析和鉴定下游靶基因，从而可以过表达或抑制该基因。我们现在将这一策略扩展到许多转录因子。特别是，在过去的一年中，我们已经将这种策略扩展到小鼠ES细胞中的其他关键转录因子（Sox 2和Nanog）。

项目成果

Transcriptome analysis of mouse stem cells and early embryos.

• DOI: 10.1371/journal.pbio.0000074
• 发表时间: 2003-12
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Sharov AA;Piao Y;Matoba R;Dudekula DB;Qian Y;VanBuren V;Falco G;Martin PR;Stagg CA;Bassey UC;Wang Y;Carter MG;Hamatani T;Aiba K;Akutsu H;Sharova L;Tanaka TS;Kimber WL;Yoshikawa T;Jaradat SA;Pantano S;Nagaraja R;Boheler KR;Taub D;Hodes RJ;Longo DL;Schlessinger D;Keller J;Klotz E;Kelsoe G;Umezawa A;Vescovi AL;Rossant J;Kunath T;Hogan BL;Curci A;D'Urso M;Kelso J;Hide W;Ko MS
• 通讯作者: Ko MS

Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.

• DOI: 10.1186/gb-2005-6-7-r61
• 发表时间: 2005
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Carter, Mark G;Sharov, Alexei A;VanBuren, Vincent;Dudekula, Dawood B;Carmack, Condie E;Nelson, Charlie;Ko, Minoru S H
• 通讯作者: Ko, Minoru S H

Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells.

• DOI: 10.1093/dnares/dsn030
• 发表时间: 2009-02
• 期刊: DNA RESEARCH
• 影响因子: 4.1
• 作者: Sharova, Lioudmila V.;Sharov, Alexei A.;Nedorezov, Timur;Piao, Yulan;Shaik, Nabeebi;Ko, Minoru S. H.
• 通讯作者: Ko, Minoru S. H.

Assignment of amyloid-precursor-like protein 2 gene (APLP2) to 11q24 by fluorescent in situ hybridization.

通过荧光原位杂交将淀粉样前体样蛋白 2 基因 (APLP2) 分配到 11q24。

• DOI: 10.1159/000015472
• 发表时间: 1999
• 期刊: Cytogenetics and cell genetics
• 作者: Leach,R;Ko,M;Krawetz,SA
• 通讯作者: Krawetz,SA

Totipotent embryonic stem cells arise in ground-state culture conditions.

• DOI: 10.1016/j.celrep.2013.04.034
• 发表时间: 2013-06-27
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Morgani SM;Canham MA;Nichols J;Sharov AA;Migueles RP;Ko MS;Brickman JM
• 通讯作者: Brickman JM