{"lab": {"status": "current", "uuid": "795847de-20b6-4f8c-ba8d-185215469cbf", "correspondence": [{"contact_email": "YmlyZW5AdWNzZC5lZHU=", "@id": "/users/e3159ffc-a5a9-43a1-8cfa-90b776c39788/", "display_title": "Bing Ren"}], "@type": ["Lab", "Item"], "display_title": "Bing Ren, UCSD", "@id": "/labs/bing-ren-lab/", "title": "Bing Ren, UCSD", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.795847de-20b6-4f8c-ba8d-185215469cbf"]}}, "award": {"name": "1U54DK107977-01", "status": "current", "@id": "/awards/1U54DK107977-01/", "display_title": "SAN DIEGO CENTER FOR 4D NUCLEOME RESEARCH", "description": "NOFIC: The complete sequencing of the human genome has provided an unprecedented opportunity for the study of the structure and function of the human genome. While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. Our highly collaborative team will draw on the diverse experiences of its members to provide a synergistic environment to push the limits of our understanding of nuclear structure. 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Analysis of the resulting paired-end short read sequences produces a matrix that shows the number of interactions between different DNA regions.\n</p>\n<p>\nAdvances in DNA sequencing depth and molecular techniques led to the development of a improved version of this technique known as in situ Hi-C that provides higher resolution, higher accuracy, and a much faster protocol. \n</p>\n<p>\nSee <a href=\"http://science.sciencemag.org/content/326/5950/289\" rel=\"noopener noreferrer\" target=\"_blank\">Lieberman-aiden et al., 2009</a> for more details on dilution Hi-C.\n</p>\n<div>\n<img src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/dHiC.png\" style=\"width: 600px;\"/>\n<br/><br/>\n<em>Image source: Lieberman-aiden et al., 2009, Figure 1A</em>\n</div></div>"}], "processed_files": [{"file_type": "contact list-combined", "file_classification": "processed file", "open_data_url": 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This duplication does not affect the higlass display of these files, howevver, downstream analyses using this file may encounter issues due to this pixel duplication.  The counts from the duplicate pixels can be aggregated to determine the correct count value at that location. If this issue is problematic for your needs you should consider regenerating the matrices from the merged pairs file of the associated dataset using a more recent version of cooler.  We are working to update the pipeline but do not yet have a predicted date for when this issue will be resolved."], "higlass_uid": "b'clA0avBcQLSdj_FOxYx_Ew'", "file_classification": "processed file", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/e6cc3f6e-71b4-4b42-91ca-11f077c0993e/4DNFI78T9N5Y.mcool", "file_format": {"@type": ["FileFormat", "Item"], "@id": "/file-formats/mcool/", "uuid": "d13d06cf-218e-4f61-ccf0-91f226248b2c", "status": "released", "display_title": "mcool", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "upload_key": "e6cc3f6e-71b4-4b42-91ca-11f077c0993e/4DNFI78T9N5Y.mcool", "genome_assembly": "GRCh38", "href": "/files-processed/4DNFI78T9N5Y/@@download/4DNFI78T9N5Y.mcool", "@type": ["FileProcessed", "File", "Item"], "accession": "4DNFI78T9N5Y", "display_title": "4DNFI78T9N5Y.mcool", "file_size": 3662890047, "file_type_detailed": "contact matrix (mcool)", "md5sum": 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"uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRX5558245"}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "last_modified": {"date_modified": "2020-10-29T22:24:21.156811+00:00"}}], "experimentset_type": "replicate", "completed_processes": ["compartments_v1.2", "insulation_scores_and_boundaries_v1", "HiC_Pipeline_0.2.7"], "other_processed_files": [], "@id": "/experiment-set-replicates/4DNESDYFTSG5/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "uuid": "c1d8ef0c-d408-4c2d-9e13-d138bcb35e81", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "4DNESDYFTSG5", "external_references": [], "produced_in_pub": {"ID": "PMID:31779666", "@id": "/publications/b8c7c5f5-c76f-457f-9a0d-6c567924b816/", "title": "Common DNA sequence variation influences 3-dimensional conformation of the human  genome.", "journal": "Genome biology", "display_title": "Gorkin DU et al. (2019) PMID:31779666", "@type": ["Publication", "Item"], "short_attribution": "Gorkin DU et al. (2019)", "uuid": "b8c7c5f5-c76f-457f-9a0d-6c567924b816", "status": "current", "date_published": "2019-11-28", "abstract": "BACKGROUND: The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. RESULTS: To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. CONCLUSION: Our  results demonstrate that common DNA sequence variants can influence 3D chromatin  conformation, pointing to a more pervasive role for 3D chromatin conformation in  human phenotypic variation than previously recognized.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/31779666", "authors": ["Gorkin DU", "Qiu Y", "Hu M", "Fletez-Brant K", "Liu T", "Schmitt AD", "Noor A", "Chiou J", "Gaulton KJ", "Sebat J", "Li Y", "Hansen KD", "Ren B"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"status": "current", "uuid": "b8c7c5f5-c76f-457f-9a0d-6c567924b816", "@type": ["Publication", "Item"], "ID": "PMID:31779666", "abstract": "BACKGROUND: The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. RESULTS: To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. CONCLUSION: Our  results demonstrate that common DNA sequence variants can influence 3D chromatin  conformation, pointing to a more pervasive role for 3D chromatin conformation in  human phenotypic variation than previously recognized.", "journal": "Genome biology", "authors": ["Gorkin DU", "Qiu Y", "Hu M", "Fletez-Brant K", "Liu T", "Schmitt AD", "Noor A", "Chiou J", "Gaulton KJ", "Sebat J", "Li Y", "Hansen KD", "Ren B"], "@id": "/publications/b8c7c5f5-c76f-457f-9a0d-6c567924b816/", "date_published": "2019-11-28", "display_title": "Gorkin DU et al. 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