Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping
使用表位靶向 DNA 甲基化作图的超灵敏多组学平台
基本信息
- 批准号:10758061
- 负责人:
- 金额:$ 103.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY
Gene expression is regulated by the complex molecular cross-talk between DNA methylation (DNAme)
and other chromatin features: e.g. histone post-translational modifications (PTMs) and chromatin associated
proteins (ChAPs; transcription factors and chromatin remodelers). Significantly, changes in the chromatin
landscape can have a profound impact on DNAme patterning (and vice versa), and these changes are connected
to development as well as a broad range of diseases (from cancer to neurological disorders). However, our
understanding of how DNAme co-occurs / coordinates with additional chromatin features to control gene
expression is limited by a lack of reliable genomic tools. Here, EpiCypher is partnering with New England Biolabs
(NEB) to develop Targeted Enzymatic Methylation-sequencing (TEM-seqTM), an ultra-sensitive multiomic
mapping technology that delivers high resolution DNAme profiles (5mC/5hmC) at epitope-defined
chromatin features. EpiCypher is leading the development of ultra-sensitive genomic mapping assays that use
CUT&RUN / CUT&Tag methods (under the CUTANA® platform) to generate truly quantitative data using
dramatically reduced cell input and sequencing depth (>10-fold savings on each parameter vs. ChIP-seq).
CUTANA assays are supported by EpiCypher’s proprietary spike-in designer nucleosome (dNuc) technology to
enable technical monitoring and quantitative normalization. The key innovation of the TEM-seq project is the
development of a novel multiomic workflow that marries EpiCypher’s quantitative CUTANA CUT&RUN
technology with unbiased DNAme analysis using NEB’s enzymatic methyl-seq (EM-seq) approach. EM-seq
utilizes the enzymatic conversion of DNAme (5mC / 5hmC) and provides a much-needed alternative to bisulfite
sequencing (BS; a chemical treatment that degrades DNA and has systemic sequence biases) to generate high
resolution, unbiased DNAme profiles with ~10-fold less sample input (vs. BS). In Phase I Aim 1, we will rigorously
validate our TEM-seq workflow in three cell lines, benchmark results against standard CUT&RUN and EM-seq
assays, and further develop EpiCypher’s spike-in controls for compatibility with TEM-seq. We will advance to
Phase II when we demonstrate that TEM-seq generates highly reliable DNAme maps associated with histone
PTMs and ChAPs using <50k cells and <10M reads. In Phase II Aim 2, we will expand development of spike-in
control panels and develop robust protocols for a wide panel of chromatin features (using validated antibodies)
and sample processing methods (fresh, frozen, and fixed), including drug treatment time-course experiments to
enable clinical applications. In Phase II Aim 3, we will develop / validate a TEM-seq beta kit, and also create a
data analysis portal and automated assays to accelerate commercial adoption and enable a high-throughput
service offering. TEM-seq will provide a powerful new tool to expand our understanding of complex chromatin
signaling, further unlocking the potential of epigenetics-targeted drugs and diagnostics.
项目总结
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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Michael-Christopher Keogh其他文献
Michael-Christopher Keogh的其他文献
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{{ truncateString('Michael-Christopher Keogh', 18)}}的其他基金
Scalable and quantitative chromatin profiling from formalin-fixed paraffin-embedded samples
对福尔马林固定石蜡包埋样品进行可扩展和定量的染色质分析
- 批准号:
10696343 - 财政年份:2023
- 资助金额:
$ 103.57万 - 项目类别:
Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping
使用表位靶向 DNA 甲基化作图的超灵敏多组学平台
- 批准号:
10833236 - 财政年份:2023
- 资助金额:
$ 103.57万 - 项目类别:
High-resolution genomic mapping of ssDNA and associated proteins for Alzheimer's disease research
用于阿尔茨海默病研究的 ssDNA 和相关蛋白的高分辨率基因组图谱
- 批准号:
10382044 - 财政年份:2022
- 资助金额:
$ 103.57万 - 项目类别:
Quantitative mapping of dynamic epigenetic states in rare and stimulated immune cells
稀有和刺激免疫细胞动态表观遗传状态的定量图谱
- 批准号:
10481225 - 财政年份:2022
- 资助金额:
$ 103.57万 - 项目类别:
Quantitative mapping of dynamic epigenetic states in rare and stimulated immune cells
稀有和刺激免疫细胞动态表观遗传状态的定量图谱
- 批准号:
10686135 - 财政年份:2022
- 资助金额:
$ 103.57万 - 项目类别:
Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping
使用表位靶向 DNA 甲基化作图的超灵敏多组学平台
- 批准号:
10384022 - 财政年份:2022
- 资助金额:
$ 103.57万 - 项目类别:
Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping
使用表位靶向 DNA 甲基化作图的超灵敏多组学平台
- 批准号:
10622310 - 财政年份:2022
- 资助金额:
$ 103.57万 - 项目类别:
A new epigenetic toolbox for inflammation research and drug discovery
用于炎症研究和药物发现的新表观遗传学工具箱
- 批准号:
10610898 - 财政年份:2021
- 资助金额:
$ 103.57万 - 项目类别:
A new epigenetic toolbox for inflammation research and drug discovery
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- 批准号:
10401943 - 财政年份:2021
- 资助金额:
$ 103.57万 - 项目类别:
A new epigenetic toolbox for inflammation research and drug discovery
用于炎症研究和药物发现的新表观遗传学工具箱
- 批准号:
10257054 - 财政年份:2021
- 资助金额:
$ 103.57万 - 项目类别:
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