- What is 4D Nucleome
- Current dilemma in understanding 4D nucleome
- Goals and Strategies
- Structure of the 4DN Network
- Data sharing and standards
To determine how the genome operates, we need to understand not only the linear encoding of information along chromosomes, but also its three-dimensional organization and its dynamics across time, that is, the ‘4D nucleome’.
- Different experimental cell systems and approaches are used that together with the absence of shared benchmarks for assay performance have led to observations that cannot be directly compared.
- Iimited ability to integrate different data types (for example, chromatin interaction data and imaging-based distance measurements)。
- Lack of approaches that can measure and account for cell-to-cell variability in chromosome and nuclear organization.
- Lack of mechanistic insights into the relationships between chromosome conformation and nuclear processes, including transcription, DNA replication and chromosome segregation.
- Develop, benchmark, validate and standardize a wide array of technologies to analyse the 4D nucleome
- Integrate, analyse and model datasets obtained with these technologies to obtain a comprehensive view of the 4D nucleome
- Investigate the functional role of various structural features of chromosome organization in transcription, DNA replication and other nuclear processes.
- A set of common cell lines will be studied to enable direct cross- validation of data that are obtained with different methods table.
- Standards for data formats and quality will be established so that data can be shared broadly.
- Computational and analytical tools will be developed to analyse individual datasets and to integrate, compare and cross-validate data obtained with different technologies.
- Develope multiple ways to measure how DNA and trans-acting factors influence on the 4D nucleosome.
- Develop a consistent terminology to describe nuclear features and biophysically derived principles guiding chromosome folding.
- Compare and integrate the wealth of information that is anticipated to be generated by the Network.
- Build a shared database and a public 4DN data browser includes all data, detailed protocols, engineered cell lines and reagents used across the Network.
Consortium | Institution Name | Objections |
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NOFIC (Nuclear Organization and Function Interdisciplinary Consortium) | UNIVERSITY OF SOUTHERN CALIFORNIAUNIV OF ILLINOIS URBANA-CHAMPAIGNUNIV OF MASSACHUSETTS MED SCH WORCESTERLUDWIG INSTITUTE FOR CANCER RESEARCH LTDJACKSON LABORATORYUNIV OF WASHINGTON | benchmark toolsFind best approachIntegrate approachesDraft model of 4DN |
Imaging Tools | YALE UNIVERSITYCALIFORNIA INSTITUTE OF TECHNOLOGYPRINCETON UNIVERSITYEUROPEAN MOLECULAR BIOLOGY LABORATORYUNIV OF MASSACHUSETTS MED SCH WORCESTERUNIVERSITY OF CALIFORNIA AT DAVISSTANFORD UNIVERSITYSALK INSTITUTE FOR BIOLOGICAL STUDIESALBERT EINSTEIN COLLEGE OF MEDICINE | High res methodHigh-throughputdynamic imagingLive cell |
DCIC (Network Data Coordination and Integration Center) | HARVARD MEDICAL SCHOOLWASHINGTON UNIVERSITY | collect, store, curate, display and analyze datadevelope efficient submission pipelineshigh-quality, well- annotated, public accessibleuser-friendly data portal |
Network Organizational Hub | UNIVERSITY OF CALIFORNIA SAN DIEGO | web portal for 4DNintegrated, bersatile data managementretrieval, analysis and vis systemtrain and update 4DN members and collaboraters |
Nuclear Bodies and Compartments | PRINCETON UNIVERSITYSCRIPPS RESEARCH INSTITUTEPRINCETON UNIVERSITYFRED HUTCHINSON CANCER RES CENTERCALIFORNIA INSTITUTE OF TECHNOLOGYUNIV OF MASSACHUSETTS MED SCH WORCESTERCOLUMBIA UNIVERSITY HEALTH SCIENCES | deciphering function of compartmentsnucleoplasmic phase transitionsreversibly disrupt nuclear bodies |
Nucleomics Tools | THE BABRAHAM INSTITUTECALIFORNIA INSTITUTE OF TECHNOLOGYBAYLOR COLLEGE OF MEDICINECORNELL UNIVERSITYUNIVERSITY OF PENNSYLVANIA | pipeline for single-cell hi-cmap dynamic organizationsplit pool barcodingdistance-Hi-Csuper resolution vis |
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Need to develope common formats to represent three-dimensional interactions.
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Efficient data structure to store sparse matrix (interaction matrix is sparse)
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Standards to unify data and metadata from different manufacturers for imaging technologies.
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Define a set of appropriate metadata fields and minimum metadata requirements such that sufficient and useful details are available to other investigators outside the Network.
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Develope a set of measures for assessing data quality and determining
appropriate thresholds.
[1] Dekker, Job, et al. "The 4D nucleome project." Nature 549.7671 (2017): 219.
[2] https://commonfund.nih.gov/4Dnucleome