Computational and Functional Analysis of Gene Networks

基因网络的计算和功能分析

• 批准号: 7076196
• 负责人: MARC S HALFON
• 金额: $ 27万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076196
• 关键词: Drosophilidae; animal genetic material tag; binding sites; biological signal transduction; computer data analysis; computer program /software; computer system design /evaluation; epidermal growth factor; fibroblast growth factor; flow cytometry; functional /structural genomics; gene expression; genetic enhancer element; genetic regulatory element; genetic transcription; growth factor receptors; mathematical model; microarray technology; molecular cloning; nucleic acid sequence; polymerase chain reaction; regulatory gene; transcription factor

DESCRIPTION: (provided by applicant) Metazoan development requires both intercellular signaling and the integration of these signals within cells to produce a transcriptional response. While many signaling pathways are well characterized, understanding on a global scale the interplay between signal transduction and gene transcription - genetic regulatory networks -remains a major challenge for current genomics research. We have explored in detail part of one such network, which specifies the fate of a subset of Drosophilamuscle and cardiac progenitor cells by the combined action of three signaling pathways, including the Ras pathway via input from both EGF and FGF receptors. The transcription factors downstream of these pathways, and tissue-specific factors induced by them, are integrated at a single transcriptional enhancer for a progenitor identity gene, the even skippedMuscle and Heart Enhancer (MHE). Therecent sequencing of the Drosophilagenome offers an exciting opportunity to extend the insights garnered from our investigation of the MHE on a genome-wide scale. Here, a computational analysis will be used to identify cis-regulatory elements that share features of the MHE and that regulate mesodermal gene expression in a similar spatiotemporal pattern. Invivo techniques, including the analysis of reporter transgenes, will be used to validate the computer predictions. The signaling component of the regulatory networks in which these cisregulatory elements act will be investigated using DNA microarrays. The respective contributions of the FGF and EGF-receptor pathways to Ras-mediated mesodermal signaling, non-Ras-mediated activities of these receptors, and the individual contributions of specific Ras transcriptional effectors will be determined, as will the combined effects of multiple growth factor signals. These approaches will significantly increase our understanding of combinatorial signaling and transcriptional responses by identifying new genes and regulatory elements, and provide insight into the genetic regulatory networks that mediate responses to signaling in a specific regulatory context. The research detailed in this proposal will provide the candidate with an ideal opportunity to apply a strong background in developmental genetics to the emerging fields of computational and functional genomics in a rich learning and research environment, in preparation for an independent academic research career.

描述：（由申请人提供）后生动物的发育需要 细胞间信号传导和这些信号在细胞内的整合， 产生转录反应。虽然许多信号通路 在全球范围内了解信号之间的相互作用， 转导和基因转录-遗传调控网络-仍然是一个 这是目前基因组学研究的一大挑战。我们已经详细探讨了部分 一个这样的网络，它指定了果蝇的一个子集的命运 和心脏祖细胞通过三种信号传导的联合作用 这些信号通路包括通过EGF和FGF受体输入的Ras通路。 这些途径下游的转录因子，以及组织特异性的 由它们诱导的因子，在单个转录增强子处整合 对于祖先身份基因，甚至跳过肌肉和心脏增强剂， （MHE）。最近的果蝇基因组测序提供了一个令人兴奋的 有机会扩展我们从MHE调查中获得的见解 在全基因组范围内。在这里，将使用计算分析来识别 顺式调节元件，其具有MHE的特征并调节 中胚层基因表达的时空模式相似。Invivo 技术，包括报告转基因的分析，将被用来 验证计算机的预测。调控信号的组成部分 这些顺式调节元件作用的网络将使用 DNA微阵列FGF和EGF受体的各自贡献 Ras介导的中胚层信号传导途径，非Ras介导的 这些受体，以及特定Ras的个体贡献， 转录效应子将被确定，以下因素的综合效应也将被确定 多种生长因子信号。这些方法将大大增加 我们对组合信号和转录反应的理解， 确定新的基因和调控元件，并提供洞察 基因调控网络，介导对特定信号传导的反应， 监管背景。 本建议书中详细的研究将为候选人提供一个理想的 有机会将发育遗传学的强大背景应用于 新兴领域的计算和功能基因组学在丰富的学习和 研究环境，为独立的学术研究做准备 事业

项目成果

Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset.

• DOI: 10.1186/gb-2005-6-2-r16
• 发表时间: 2005
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Choe SE;Boutros M;Michelson AM;Church GM;Halfon MS
• 通讯作者: Halfon MS

An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

• DOI: 10.1371/journal.pgen.0020016
• 发表时间: 2006-02
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Estrada B;Choe SE;Gisselbrecht SS;Michaud S;Raj L;Busser BW;Halfon MS;Church GM;Michelson AM
• 通讯作者: Michelson AM

REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila.

• DOI: 10.1093/nar/gkm876
• 发表时间: 2008-01
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Halfon MS;Gallo SM;Bergman CM
• 通讯作者: Bergman CM

Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs.

• DOI: 10.1186/gb-2008-9-1-r22
• 发表时间: 2008-01-28
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Ivan, Andra;Halfon, Marc S.;Sinha, Saurabh
• 通讯作者: Sinha, Saurabh

Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster.

• DOI: 10.1186/1471-2164-10-9
• 发表时间: 2009-01-07
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Zhu Q;Halfon MS
• 通讯作者: Halfon MS