High-throughput Discovery of Novel Genome Organization Regulators
新型基因组组织调节因子的高通量发现
基本信息
- 批准号:10777403
- 负责人:
- 金额:$ 29.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-20 至 2024-09-19
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAffectAlgorithmsBindingBinding ProteinsBinding SitesBoundary ElementsCCCTC-binding factorCandidate Disease GeneCategoriesCell LineChromatinChromatin LoopClustered Regularly Interspaced Short Palindromic RepeatsComplexConsumptionDNADiseaseElementsEnhancersFrequenciesFundingFutureGene ExpressionGene Expression RegulationGenesGeneticGenetic ScreeningGenomeHi-CHumanHuman BioMolecular Atlas ProgramInterphaseInterphase ChromosomeInvestigationKnock-outKnowledgeMeasuresMediatingNatureNetwork-basedNeural Network SimulationPilot ProjectsProcessRegulationRegulatory ElementReporterResolutionResourcesStandardizationStructureSystemT-LymphocyteTechnologyUnited States National Institutes of HealthValidationWorkYY1 Transcription Factoracute T-cell lymphoblastic leukemia cellcell typechromosome conformation capturecohesindeep neural networkdenoisingdesignepigenomicsexperimental studyfollow-upgenomic datain silicomultimodalitynovelprogramspromoterreverse geneticsscale upscreening
项目摘要
ABSTRACT
CTCF binding at its convergent-orientated DNA motifs has been implicated in establishing TAD boundary. CTCF
protein regulates the genome organization through cohesin complex-mediated loop extrusion mechanism. While
a few more factors have been recently discovered to regulate genome organization, such as NIPBL, WAPL, YY1,
ZNF143, and MAZ, it is still far from a comprehensive mechanistic understanding of how the genome is organized.
Discovering novel regulators of genome organization is still challenging due to the intensive nature of chromatin
conformation capture technologies. To address the technical challenge in measuring genome organization, we
have recently demonstrated that a deep neural network approach can enable de novo prediction of cell type-
specific chromatin organization at high resolution. Moreover, this deep neural network model enables high-
throughput in silico genetic screen (ISGS) for identifying cell type-specific DNA elements that are important for
chromatin interactions. To fully unlock the discovery potential of this deep neural network-based ISGS approach,
here we propose to leverage the NIH Common Fund-supported large-scale genomic data across human bio-
samples for discovering novel regulators in 3D genome organization. We will predict a list of high-confidence
trans-acting regulators, and experimentally validate 3-5 top hits in pilot studies to generate cross-cutting
hypotheses for future research in 3D genome regulation.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Bo Xia其他文献
Bo Xia的其他文献
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{{ truncateString('Bo Xia', 18)}}的其他基金
Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
- 批准号:
10705110 - 财政年份:2022
- 资助金额:
$ 29.27万 - 项目类别:
Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
- 批准号:
10894990 - 财政年份:2022
- 资助金额:
$ 29.27万 - 项目类别:
Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
- 批准号:
10481466 - 财政年份:2022
- 资助金额:
$ 29.27万 - 项目类别:
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