A Comprehensive Genomic Community Resource of Transcriptional Regulation

转录调控的综合基因组群落资源

基本信息

  • 批准号:
    10625529
  • 负责人:
  • 金额:
    $ 80.94万
  • 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:
    2022-06-01 至 2027-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract The Human Genome Project (HGP) completed the first draft human genome sequence two decades ago. The HGP revealed that human complexity arises from only approximately 20,000 coding genes, roughly the same number as much simpler organisms such as nematodes. Intricate patterns of transcriptional regulation mediated by non-coding regulatory elements specify the myriad cell types and states required for human complexity. Genome-wide association studies have subsequently identified thousands of disease-associated variants, many of which interrupt the function of these non-coding elements to disrupt transcriptional regulation. Thus, in order to better understand human physiology and pathophysiology, comprehensive atlases of regulatory elements are essential. Many previous efforts, including the International Human Epigenome Consortium (IHEC), the FANTOM Consortium, the Roadmap Epigenomics Project, and the ENCODE Project, have aimed to build comprehensive collections of regulatory elements, as well as computational models to better predict regulatory activity and understand the sequence features underlying regulatory function. ENCODE (2003-2022) is a large- scale consortium effort which aims to annotate every functional non-coding element of the human genome; during our work on the project, we built a Registry of approximately 1 million human candidate cis-regulatory elements (cCREs). We further developed deep-learning approaches which model the transcription factor motif syntax that underlies element function at base-pair resolution and built two web-based resources, SCREEN and Factorbook, to make our results accessible to the scientific community. Here, we propose to extend this framework to build the Community Resource for Transcriptional Regulation (CRTR), a comprehensive atlas of non-coding regulatory elements and machine-learning models which will encompass community and consortium deep-sequencing data, both bulk and single cell, across a broad array of cell types and states. Our project has five aims. First, we aim to curate community and consortium data for inclusion in CRTR and perform uniform processing and quality control. Second, we aim to train deep-learning sequence models on bulk epigenetic datasets to identify transcription factor motif syntax driving regulatory element activity in distinct tissues and cell types. Third, we aim to train sequence models on single cell datasets to identify transcription factor motif syntax driving transcriptional regulation in high-resolution cell states and during cell state transitions. Fourth, we aim to use the aforementioned results to build comprehensive benchmark datasets and machine-learning model collections, which will aid future analysts in designing new models to predict regulatory readouts. Fifth, we aim to build a state-of-the-art web-based user interface to enable users to perform integrative analyses and in silico experimentation with CRTR, and hold workshops and other outreach to maximize the impact of the resource and its accessibility to the broader scientific community.
项目总结/文摘

项目成果

期刊论文数量(0)
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Anshul Kundaje其他文献

Anshul Kundaje的其他文献

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{{ truncateString('Anshul Kundaje', 18)}}的其他基金

Multi-Omics DACC: The Data Analysis and Coordination Center for the collaborative multi-omics for health and disease initiative
多组学 DACC:健康和疾病协作多组学计划的数据分析和协调中心
  • 批准号:
    10744561
  • 财政年份:
    2023
  • 资助金额:
    $ 80.94万
  • 项目类别:
A Comprehensive Genomic Community Resource of Transcriptional Regulation
转录调控的综合基因组群落资源
  • 批准号:
    10411262
  • 财政年份:
    2022
  • 资助金额:
    $ 80.94万
  • 项目类别:
A Comprehensive Genomic Community Resource of Transcriptional Regulation
转录调控的综合基因组群落资源
  • 批准号:
    10842047
  • 财政年份:
    2022
  • 资助金额:
    $ 80.94万
  • 项目类别:
Identifying causal genetic variants and molecular mechanisms impacting mental health
识别影响心理健康的因果遗传变异和分子机制
  • 批准号:
    10571911
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Identifying causal genetic variants and molecular mechanisms impacting mental health
识别影响心理健康的因果遗传变异和分子机制
  • 批准号:
    10380573
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory code
通过顺式调控密码的视角预测遗传变异的特定背景分子和表型效应
  • 批准号:
    10659170
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory code
通过顺式调控密码的视角预测遗传变异的特定背景分子和表型效应
  • 批准号:
    10297562
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory code
通过顺式调控密码的视角预测遗传变异的特定背景分子和表型效应
  • 批准号:
    10474459
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologies
使用高通量和单细胞技术对新型 AD 变体进行多组学功能评估
  • 批准号:
    10684210
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologies
使用高通量和单细胞技术对新型 AD 变体进行多组学功能评估
  • 批准号:
    10217784
  • 财政年份:
    2021
  • 资助金额:
    $ 80.94万
  • 项目类别:

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