Recent technological developments have significantly advanced our understanding of the three-dimensional organization of the nucleus. It has also become increasingly clear that the 3D nucleome plays an important role in regulating gene expression. Large cohorts of data are being generated to investigate the impact of the temporal changes of nuclear organization (the 4D nucleome) to normal development and disease processes. The primary goal of this proposal is the creation of an effective organizational hub and web portal for the 4D nucleome. We also propose to develop an effective coordination structure for the 4D nucleome activities. First, we will develop and organize effective networking methods and consortium meetings for establishing protocols and standards. We will develop a framework for coordination of the funded 4D nucleome projects. We will organize annual consortium-wide grantees meeting. We will utilize the professional organizers who have previously worked with the PIs and the premium conference venues at Atkinson Hall in UCSD (www.calit2.net). Two major activities will be organized during the annual meeting. Second, we will develop an adaptable, scalable, and user-friendly 4DN web portal. We will build the 4DN Network community web portal and a Virtual Resource Repository. This portal will be an integrated, versatile, and inter-operable data management, retrieval, analysis, and visualization system. We will leverage the ENCODE Comparative Browser (http://encode.cepbrowser.org) for developing the 4D network portal. In addition, the portal will incorporate data generated from outside the consortium, publish E-manuals for the consortium-agreed protocols, and provide the most up-to-date information on the data clearance. Third, we will coordinate and manage the 4DN Network Opportunity Pool. The opportunity pool of funds will be distributed and managed with 100% transparency. Competitive distribution with the funds will be coordinated by a professional manager with extensive experience in managing Center and Training Grants. Fourth, we will develop a comprehensive strategy for training and outreach. The proposed unit will aim to regularly train and update 4DN research network members and collaborators in several key areas including: 1) new technologies; 2) data/sample collection protocols; 3) data analysis methods; 4) data submission protocols; 5) data retrieval methods; 6) data QA/QC; 7) data exchange standards and data ontologies; 8) the contents of different 4DN and public databases; 9) data privacy and 10) data dissemination.

Public Health Relevance

With the advent of modern technologies that directly and indirectly provide readouts of the chromatin 3D structure vis--vis specific gene-encoding and regulatory regions. Time and environmental influences add another dimension for understanding spatiotemporal organization of the nucleus. This organizational hub will be dedicated to facilitate the discovery of the pivotal role of the 4D nucleome in cell identity, organismal development and disease processes, potential roles in cognition and behavior as well as in personal variations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA200147-03
Application #
9344559
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mietz, Judy
Project Start
2015-09-01
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Calandrelli, Riccardo; Wu, Qiuyang; Guan, Jihong et al. (2018) GITAR: An Open Source Tool for Analysis and Visualization of Hi-C Data. Genomics Proteomics Bioinformatics :
Sabath, Niv; Vilborg, Anna; Steitz, Joan A et al. (2018) Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal. Hum Genomics 12:32
Cao, Xiaoyi; Yan, Zhangming; Wu, Qiuyang et al. (2018) GIVE: portable genome browsers for personal websites. Genome Biol 19:92
Chen, Weizhong; Yan, Zhangming; Li, Simin et al. (2018) RNAs as Proximity-Labeling Media for Identifying Nuclear Speckle Positions Relative to the Genome. iScience 4:204-215
Zheng, Xiaoqi; Zhong, Sheng (2017) From structure to function, how bioinformatics help to reveal functions of our genomes. Genome Biol 18:183
Dekker, Job; Belmont, Andrew S; Guttman, Mitchell et al. (2017) The 4D nucleome project. Nature 549:219-226
Mukund, Kavitha; Subramaniam, Shankar (2017) Co-expression Network Approach Reveals Functional Similarities among Diseases Affecting Human Skeletal Muscle. Front Physiol 8:980