Encoding genomic architecture in the encyclopedia: linking DNA elements, chromatin state, and gene expression in 3D
Encoding genomic architecture in the encyclopedia: linking DNA elements, chromatin state, and gene expression in 3D
批准号:
10241049
负责人:
Christina S Leslie
金额:
$74.25万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-02-01 至 2022-01-31
关键词:
3-DimensionalATAC-seqArchitectureAtlasesCellsChromatinChromatin Interaction Analysis by Paired-End Tag SequencingChromatin LoopChromosomesClustered Regularly Interspaced Short Palindromic RepeatsComputing MethodologiesDNADNA SequenceDNA StructureDNase I hypersensitive sites sequencingDataDiseaseElementsEncyclopediasEnhancersEpigenetic ProcessGene ExpressionGene Expression RegulationGenesGenetic TranscriptionGenomeGenomicsGoalsGrantGuide RNAHi-CHumanHuman GenomeHybridsIndividualLearningLightLinkMediatingMethodsModelingOutputParentsPeptide Signal SequencesPloidiesPublished CommentRegulationRegulator GenesRegulatory ElementResolutionResourcesSpecificityStatistical Data InterpretationStructural ModelsStructureTechnologyTrainingUntranslated RNAbasecell typechromosome conformation capturecomputerized toolsdeep learningdensityepigenomicsexperimental studygenome annotationgenome editinggenome wide association studygenomic datahistone modificationinsightlearning strategymembernext generationpredictive modelingprogramssequence learningsupervised learningthree dimensional structurethree-dimensional modelingtooltranscription factortranscriptomicsunsupervised learning
中文摘要
自提交U 01母补助金以来,这一部分没有改变。
项目摘要
由ENCODE生成的1000多个测序实验中的大多数提供了表观遗传的1D读数。
3D基因组的横向或转录输出。新的染色体构象捕获(3C)
技术-特别是Hi-C和ChIA-PET -已经开始提供对分层3D的深入了解
基因组的组织:染色体分成开放和封闭的区室;
定义为拓扑相关结构域(TADs)的结构亚基;以及调节和
TADs内的结构DNA环。使用CRISPR/Cas介导的基因组编辑的新实验证据
表明局部3D结构的破坏可以改变邻近基因的调节,并且已经有
使用3D DNA循环数据来预测GWAS研究中非编码SNP的影响的早期努力。
该提案的目标是开发新的综合计算方法来解释大规模的
ENCODE 1D表观基因组和转录组学资源,基于
基因组我们团队的成员开创了强大的方法来推断局部染色质状态从一维
通过赛格威套件的观点。我们还分析了染色质的1D组织,
元素及其谱系动力学来定义调控复杂性的概念,我们提出了一个基因
调控模型,以预测基因表达的变化,在分化的DNA含量的活性
增强剂。在这里,我们将建立在这些努力,学习染色质状态和基因调控模型,
结合分层3D基因组结构的信息,使我们能够预测个体
结构/调控元件有助于3D DNA成环和基因表达。机械预测
将使用最先进的技术在其天然细胞类型特异性染色质背景下进行实验验证
基因组编辑,利用我们团队开发的计算和实验CRISPR/Cas工具。
英文摘要
This section has not changed since the submission of the parent U01 grant.
Project Summary
Most of the 1000s of sequencing experiments generated by ENCODE provide 1D readouts of the epigenetic
landscape or transcriptional output of a 3D genome. New chromosome conformation capture (3C)
technologies – in particular Hi-C and ChIA-PET – have begun to provide insight into the hierarchical 3D
organization of the genome: the partition of chromosomes into open and closed compartments; the existence
of structural subunits defined as topologically associated domains (TADs); and the presence of regulatory and
structural DNA loops within TADs. New experimental evidence using CRISPR/Cas-mediated genome editing
suggests that disruption of local 3D structure can alter regulation of neighboring genes, and there have been
early efforts to use data on 3D DNA looping to predict the impact of non-coding SNPs from GWAS studies.
The goal of this proposal is to develop new integrative computational methods to interpret large-scale
ENCODE 1D epigenomic and transcriptomic resources in light of the underlying 3D architecture of the
genome. Members of our team have pioneered powerful methods to infer local chromatin states from a 1D
viewpoint through the Segway suite. We have also analyzed the 1D organization of chromatin accessible
elements and their lineage dynamics to define the concept of regulatory complexity, and we presented a gene
regulation model to predict gene expression changes in differentiation from the DNA content of active
enhancers. Here we will build on these efforts to learn chromatin state and gene regulation models that
incorporate information on hierarchical 3D genomic architecture, enabling us to predict how individual
structural/regulatory elements contribute to 3D DNA looping and to gene expression. Mechanistic predictions
will be experimentally validated in their native cell-type specific chromatin context using state-of-the-art
genome editing, exploiting computational and experimental CRISPR/Cas tools developed by our team.
期刊论文(14)
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DOI:
10.1038/s41467-021-23749-x
发表时间:
2021-06-07
期刊:
Nature communications
影响因子:
16.6
作者:
[Sahin M, Wong W, Zhan Y, Van Deynze K, Koche R, Leslie CS]
通讯作者:
Leslie CS
DOI:
10.1186/s13059-023-02934-9
发表时间:
2023-06-06
期刊:
Genome biology
影响因子:
12.3
作者:
[]
通讯作者:
DOI:
10.1101/gr.275870.121
发表时间:
2022-05
期刊:
Genome research
影响因子:
7
作者:
[Karbalayghareh A, Sahin M, Leslie CS]
通讯作者:
Leslie CS
DOI:
10.1186/s13059-020-02177-y
发表时间:
2020-11-19
期刊:
Genome biology
影响因子:
12.3
作者:
[Schreiber J, Singh R, Bilmes J, Noble WS]
通讯作者:
Noble WS
Linking cells across single-cell modalities by synergistic matching of neighborhood structure.
通过邻域结构的协同匹配跨单细胞模式连接细胞。
DOI:
10.1093/bioinformatics/btac481
发表时间:
2022
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
作者:
[Hristov,BorislavH, Bilmes,JeffreyA, Noble,WilliamStafford]
通讯作者:
Noble,WilliamStafford
共 8 条
The Center for Tumor-Immune Systems Biology at MSKCC
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批准号:10525190
-
项目类别:
-
资助金额:$265.5万
-
财政年份:2022
-
负责人:Christina S Leslie
-
依托单位:
Administrative Core
-
批准号:10525191
-
项目类别:
-
资助金额:$28.32万
-
财政年份:2022
-
负责人:Christina S Leslie
-
依托单位:
The Center for Tumor-Immune Systems Biology at MSKCC
-
批准号:10705726
-
项目类别:
-
资助金额:$260.19万
-
财政年份:2022
-
负责人:Christina S Leslie
-
依托单位:
Administrative Core
-
批准号:10705771
-
项目类别:
-
资助金额:$40.71万
-
财政年份:2022
-
负责人:Christina S Leslie
-
依托单位:
Deciphering the Genomics of Gene Network Regulation of T Cell and Fibroblast States in Autoimmune Inflammation
-
批准号:10472615
-
项目类别:
-
资助金额:$128.0万
-
财政年份:2021
-
负责人:Christina S Leslie
-
依托单位:
Deciphering the Genomics of Gene Network Regulation of T Cell and Fibroblast States in Autoimmune Inflammation
-
批准号:10305241
-
项目类别:
-
资助金额:$128.0万
-
财政年份:2021
-
负责人:Christina S Leslie
-
依托单位:
Deciphering the Genomics of Gene Network Regulation of T Cell and Fibroblast States in Autoimmune Inflammation
-
批准号:10621786
-
项目类别:
-
资助金额:$128.0万
-
财政年份:2021
-
负责人:Christina S Leslie
-
依托单位:
Systems biology of the tumor immune microenvironment
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批准号:10415307
-
项目类别:
-
资助金额:$33.09万
-
财政年份:2021
-
负责人:Christina S Leslie
-
依托单位:
Encoding genomic architecture in the encyclopedia: linking DNA elements, chromatin state, and gene expression in 3D
-
批准号:9247342
-
项目类别:
-
资助金额:$71.73万
-
财政年份:2017
-
负责人:Christina S Leslie
-
依托单位:
The CSBC Research Center for Cancer Systems Immunology at MSKCC
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批准号:9343109
-
项目类别:
-
资助金额:$17.14万
-
财政年份:2016
-
负责人:Christina S Leslie
-
依托单位:
The CSBC Research Center for Cancer Systems Immunology at MSKCC
-
批准号:9980798
-
项目类别:
-
资助金额:$231.25万
-
财政年份:2016
-
负责人:Christina S Leslie
-
依托单位:
The CSBC Research Center for Cancer Systems Immunology at MSKCC
-
批准号:9186246
-
项目类别:
-
资助金额:$211.91万
-
财政年份:2016
-
负责人:Christina S Leslie
-
依托单位:
Modeling the impact of mutations in ubiquitin ligase genes on transcriptional programs in endometrial cancer
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批准号:9246450
-
项目类别:
-
资助金额:$18.64万
-
财政年份:2016
-
负责人:Christina S Leslie
-
依托单位:
Administrative Core
-
批准号:9980800
-
项目类别:
-
资助金额:$33.63万
-
财政年份:2016
-
负责人:Christina S Leslie
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依托单位:
Decoding in vivo regulatory programs of CD4+ T lymphocyte populations in inflamma
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批准号:9178029
-
项目类别:
-
资助金额:$103.47万
-
财政年份:2015
-
负责人:Christina S Leslie
-
依托单位:
Decoding in vivo regulatory programs of CD4+ T lymphocyte populations in inflamma
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批准号:8770949
-
项目类别:
-
资助金额:$103.44万
-
财政年份:2015
-
负责人:Christina S Leslie
-
依托单位:
Decoding in vivo regulatory programs of CD4+ T lymphocyte populations in inflamma
-
批准号:8991719
-
项目类别:
-
资助金额:$103.33万
-
财政年份:2015
-
负责人:Christina S Leslie
-
依托单位:
Integrative analysis tools to dissect cell-type specific transcriptional programs
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批准号:8628862
-
项目类别:
-
资助金额:$52.07万
-
财政年份:2012
-
负责人:Christina S Leslie
-
依托单位:
Integrative analysis tools to dissect cell-type specific transcriptional programs
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批准号:8311335
-
项目类别:
-
资助金额:$55.63万
-
财政年份:2012
-
负责人:Christina S Leslie
-
依托单位:
Integrative analysis tools to dissect cell-type specific transcriptional programs
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批准号:8463019
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项目类别:
-
资助金额:$49.35万
-
财政年份:2012
-
负责人:Christina S Leslie
-
依托单位:
国内基金
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