PRODIGE: A high-throughput tool for joint profiling of protein-DNA interactions and gene expression in single cells
PRODIGE:一种高通量工具,用于联合分析单细胞中蛋白质-DNA 相互作用和基因表达
基本信息
- 批准号:10492769
- 负责人:
- 金额:$ 22.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-30 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAntibodiesBar CodesBenchmarkingBindingBiological AssayCell Differentiation processCell LineCellsChromatinClinicalComplexDNADNA-Binding ProteinsDNA-Protein InteractionDataData SetDevelopmentDiseaseDropsEpigenetic ProcessGene ExpressionGenesGenetic TranscriptionGenomeGenomicsHeterogeneityHistonesHydrogelsIndividualJointsLibrariesMaintenanceMapsMeasurementMeasuresMediatingMessenger RNAMethodsMicrofluidic MicrochipsMicrofluidicsModalityModelingMolecularOutputPatternPerformancePhenotypePlayPoly APopulationPost-Translational Protein ProcessingProcessProtein AnalysisProteinsProtocols documentationRNARegulator GenesReportingReproducibilityResearch PersonnelResolutionRoleSamplingSystemTechniquesTechnologyTestingTissuescancer cellcell fixationcell typecomputational pipelinesdata analysis pipelinedroplet sequencingepigenomicsgenetic manipulationgenome-widehistone modificationinsightinterestmethylomemultiple omicsnext generationnext generation sequencingnovelprogramsprotein profilingsingle-cell RNA sequencingtooltranscription factortranscriptome
项目摘要
PROJECT SUMMARY/ABSTRACT
Protein-DNA interactions control access to genes in chromatins and regulate the spatial- and temporal-specific
gene expression. These interactions are crucial for cell differentiation and the maintenance of cellular diversity.
Dysregulated patterns of protein-DNA interactions are often associated with disease states. Applications of next-
generation epigenomic sequencing techniques have enabled deconvolution of protein-DNA interactions at
single-cell level. However, it remains challenging to define how cell-to-cell heterogeneity in protein-DNA
interactions impacts gene expression variability. Currently available methods for joint profiling protein-DNA
interactions and gene expression from single cells require laborious genetic manipulation, suffer relatively low
throughput, and are impossible to specifically map proteins with post-translational modifications, such as histone
marks. To address these unmet needs, we propose to develop PRODIGE – a high-throughput tool for joint
profiling of protein-DNA interactions and gene expression in the same single cells without the need of genetic
manipulations. It is enabled by a strategic integration of reversible cell fixation, antibody-guided chromatin
tagmentation, novel deformable and degradable barcoded hydrogel beads, droplet microfluidics, and next-
generation sequencing technology. In Aim 1, we will develop technical components and analytical pipelines of
PRODIGE. We will prepare protein A-Tn5 transposome for antibody-guided Tn5 tagmentation, fabricate
microfluidic devices for single-cell PRODIGE assay, and synthesize a barcoded library of deformable and
degradable barcoded hydrogel beads for single-cell barcoding. In Aim 2, we will optimize the method in bulk and
single-cell levels, and assess the performance of PRODIGE (joint analysis) in comparison to other stand-alone
counterparts. In Aim 3, we will benchmark PRODIGE to established tools for joint single-cell profiling of protein-
DNA interactions and transcriptome. Successful implementation of the proposed program will deliver a high-
throughput tool to quantify how cell-to-cell heterogeneity in protein-DNA binding influences gene expression
variability, decipher cell-type-specific patterns of upstream protein-DNA interactions and their transcriptional
outputs, and identify protein-mediated mechanisms that regulate cell-type-associated transcriptional programs
in heterogeneous cell populations and under different developmental and/or disease conditions.
项目总结/文摘
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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Wei Wei其他文献
Random sampling in shift invariant spaces
平移不变空间中的随机采样
- DOI:
10.1016/j.jmaa.2012.08.030 - 发表时间:
2013-02 - 期刊:
- 影响因子:1.3
- 作者:
Yang Jianbin;Wei Wei - 通讯作者:
Wei Wei
Differential Protection for an Outgoing Transformer of Large-Scale Doubly Fed Induction Generator-Based Wind Farms
大型双馈感应发电机出线变压器差动保护
- DOI:
10.3390/en7095566 - 发表时间:
2014-08 - 期刊:
- 影响因子:3.2
- 作者:
Bingtuan Gao;Wei Wei;Luoma Zhang;Ning Chen;Yingjun Wu;Yi Tang - 通讯作者:
Yi Tang
Wei Wei的其他文献
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{{ truncateString('Wei Wei', 18)}}的其他基金
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- 批准号:
10684704 - 财政年份:2021
- 资助金额:
$ 22.88万 - 项目类别:
PRODIGE: A high-throughput tool for joint profiling of protein-DNA interactions and gene expression in single cells
PRODIGE:一种高通量工具,用于联合分析单细胞中蛋白质-DNA 相互作用和基因表达
- 批准号:
10303542 - 财政年份:2021
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Liquid biopsy-based toolkits for neoantigen and cognate TCR discovery for cancer immunotherapy
基于液体活检的工具包,用于癌症免疫治疗的新抗原和同源 TCR 发现
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Profiling fatty acid uptake and activity in single tumor cells
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Circuit mechanisms for encoding naturalistic motion in the mammalian retina
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Circuit mechanisms for encoding naturalistic motion in the mammalian retina
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Circuit mechanisms for encoding naturalistic motion in the mammalian retina
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Synaptic basis of motion detection in the retina
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- 资助金额:
$ 22.88万 - 项目类别:
Synaptic basis of motion detection in the retina
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- 批准号:
9204836 - 财政年份:2014
- 资助金额:
$ 22.88万 - 项目类别:
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