{"lab": {"status": "current", "uuid": "abd48785-b0e5-4453-be14-30d37a516bf3", "display_title": "Yijun Ruan, JAX", "title": "Yijun Ruan, JAX", "@id": "/labs/yijun-ruan-lab/", "@type": ["Lab", "Item"], "correspondence": [{"contact_email": "eWlqdW4ucnVhbkBqYXgub3Jn", "@id": "/users/d8ac229e-ec08-4411-be38-dc779520ea62/", "display_title": "Yijun Ruan"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.abd48785-b0e5-4453-be14-30d37a516bf3"]}}, "award": {"uuid": "029a2578-43dc-4343-8f41-694518cce304", "center_title": "NOFIC - Ruan", "@type": ["Award", "Item"], "description": "NOFIC: This proposal seeks to fulfill a community need for a comprehensive, high-resolution genome-mapping platform that will enable investigation of the structural, functional and spatiotemporal organization of the human genome. Our ultimate goal is to deliver complex chromatin interaction network maps in the context of 3D genome structures from which the dynamics of individual genomic elements can be monitored and referenced. Here, we propose to develop a Nucleome Positioning System (NPS)-comprised of 1) a robust genome- wide mapping technology platform, 2) advanced computational modeling algorithms and 3) state-of-the-art nuclear imaging methods-that will allow users community-wide to uncover the regulatory functions of 3D genome organization in human cells. NPS will be based upon the established ChIA-PET method (1,2), enhanced by process optimizations-i.e., microfluidic-based miniaturization and Tn5-transposase-based library preparation-to facilitate the study of chromatin interactions mediated by protein factors across a broader range of human cell types (Aim 1, see also Mapping Technology Development Component). We will also optimize RICh-PET for the comprehensive mapping of chromatin interactions mediated by non-coding RNAs (Aim 1). The high-quality mapping data generated through these optimization efforts will be analyzed by a new computational platform (Three-Dimensional Nucleome Modeling Engine, or 3D-NOME) that makes use of hierarchical multi-scaling to model 3D genome structures (Aim 2, Data Analysis and Modeling component). We will also complement the 3D modeling with transcriptome, epigenome and SNP data associated with genetic diseases (GWAS) to provide functional annotation to structural units (Aim 2). We will continue by developing strategies to validate the nucleome geometry predicted by 3D-NOME both structurally, using new nuclear imaging technologies, and functionally, using cutting-edge genome- and epigenome-editing approaches, in both human cell lines and mouse models (Aim 3, Biological Validation Component). Finally, we will implement NPS to generate pilot 3D genome maps from a wide range of human cell lines and primary immune cells sorted from whole blood, to elucidate the spatiotemporal dynamics of human genome organization over major developmental and hematopoietic cell lineages, as well as among differentiating lymphocytes involved in the immune response (Aim 4, Data Generation Component). Together, these efforts will yield a powerful set of sophisticated, high-quality tools and mapping data for the larger research community, and will help establish the standards for future 3D/4D nucleome studies. They will also provide insights into the broad mechanisms that organize the structure and regulate the function of the human genome, as well as the specific mechanisms by which immune responses are regulated at the nuclear level.", "project": "4DN", "display_title": "NUCLEOME POSITIONING SYSTEM FOR SPATIOTEMPORAL GENOME ORGANIZATION AND REGULATION", "name": "1U54DK107967-01", "status": "current", "@id": "/awards/1U54DK107967-01/", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "aliases": ["ruan-lab:HFFc6_RNAPII"], "accession": "4DNESI1WZ5HT", "condition": "RNA PolII", "description": "RNAPII ChIA-PET in HFFc6", "date_created": "2019-02-14T00:50:12.594986+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "ChIA-PET in HFFc6", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2020-06-17T10:05:21.566395+00:00"}, "public_release": "2019-12-03", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"display_title": "in situ ChIA-PET against RNA Pol II on HFFc6 (Tier 1) - 4DNEXCVA77CO", "@id": "/experiments-chiapet/4DNEXCVA77CO/", "@type": ["ExperimentChiapet", "Experiment", "Item"], "status": "released", "uuid": "376889ab-31d2-402d-8cdb-e9b60513811a", "accession": "4DNEXCVA77CO", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"display_title": "in situ ChIA-PET against RNA Pol II on HFFc6 (Tier 1) - 4DNEXFRRS436", "@id": "/experiments-chiapet/4DNEXFRRS436/", "@type": ["ExperimentChiapet", "Experiment", "Item"], "status": "released", "uuid": "3115d106-4a8e-4bc4-ad32-f532624ec360", "accession": "4DNEXFRRS436", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_headers": [{"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "\n**Data Use Guidelines:** This is a data set generated by the \n4DN Network and made freely available to the scientific \ncommunity. If you are intending to use these data for a \npublication, we ask that you please contact the data \ngenerating lab to discuss possible coordinated publication. \nIn your manuscript, please cite the 4DN White Paper \n([doi:10.1038/nature23884](https://doi.org/10.1038/nature23884)) \nand the 4DN Data Portal paper \n([doi:10.1038/s41467-022-29697-4](https://doi.org/10.1038/s41467-022-29697-4)), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the [Data Coordination and Integration Center](mailto:support@4dnucleome.org).", "name": "item-page-headers.ExperimentSet.data-usage-guidelines", "award": {"uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "status": "current", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Data Usage Guidelines", "status": "released", "aliases": [], "options": {"filetype": "md", "title_icon": "exclamation-circle", "collapsible": false, "default_open": true}, "date_created": "2018-08-06T03:09:55.543206+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2022-05-09T09:31:34.537494+00:00"}, "schema_version": "2", "@id": "/static-sections/621e8359-3885-40ce-965d-91894aa7b758/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "621e8359-3885-40ce-965d-91894aa7b758", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267228139"]}, "display_title": "Data Usage Guidelines", "external_references": [], "content": "\n**Data Use Guidelines:** This is a data set generated by the \n4DN Network and made freely available to the scientific \ncommunity. If you are intending to use these data for a \npublication, we ask that you please contact the data \ngenerating lab to discuss possible coordinated publication. \nIn your manuscript, please cite the 4DN White Paper \n([doi:10.1038/nature23884](https://doi.org/10.1038/nature23884)) \nand the 4DN Data Portal paper \n([doi:10.1038/s41467-022-29697-4](https://doi.org/10.1038/s41467-022-29697-4)), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the [Data Coordination and Integration Center](mailto:support@4dnucleome.org).", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p><strong>Data Use Guidelines:</strong> This is a data set generated by the \n4DN Network and made freely available to the scientific \ncommunity. If you are intending to use these data for a \npublication, we ask that you please contact the data \ngenerating lab to discuss possible coordinated publication. \nIn your manuscript, please cite the 4DN White Paper \n(<a href=\"https://doi.org/10.1038/nature23884\" rel=\"noopener noreferrer\" target=\"_blank\">doi:10.1038/nature23884</a>) \nand the 4DN Data Portal paper \n(<a href=\"https://doi.org/10.1038/s41467-022-29697-4\" rel=\"noopener noreferrer\" target=\"_blank\">doi:10.1038/s41467-022-29697-4</a>), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the <a href=\"mailto:support@4dnucleome.org\">Data Coordination and Integration Center</a>.</p></div>"}, {"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "**ChIA-PET**\n\nChIA-PET is a method for detecting the pairwise chromatin \ninteractions mediated by a specific protein of interest, and \nLong-Read ChIA-PET is the second version of this assay (and \nis used for the ChIA-PET experiments in the 4DN data portal).\n The name \u201clong read\u201d is relative to the original ChIA-PET \nprotocol ([Fullwood et al., 2009](https://www.ncbi.nlm.nih.gov/pubmed/19890323)) \nthat used a Type IIS restriction enzyme (MmeI) to generate \n\u201cshort read\u201d (2x20 bp) paired-end tags (PET) from the \nchromatin DNA templates by proximity ligation. The key \nmodifications of Long-Read ChIA-PET from the original \nChIA-PET method are 1) the use of Tn5 transposase to cut the \nproximity-ligated chromatin DNA fragments randomly, \ngenerating longer DNA templates for sequencing analysis by \npaired-end reads (2x150 bp). Therefore, most of the PET reads\n are up to 200 bp in length by 2x200 bp paired End reading \nmodel by ILLUMINA sequencing. A minor change in the protocol \nis to use one \u201cbridge\u201d linker instead of two \u201cA-B\u201d linkers, \nfurther simplifying the protocol.  \n\nThe protocol involves dual-crosslinking the cells with \nformaldehyde and EGS to fix potential contacts between \nphysically proximal regions.  Subsequently, both the cell and \nnuclear membranes are lysed, and the fragmentation step \nfollows.  An antibody is used to pull down interactions \ninvolving a specific protein factor.  The resulting chromatin \nmaterial goes through the proximity ligation by A-tailing and \nlinker ligation.  Reverse crosslinking removes the protein, \nleaving the DNA fragments to be amplified and sequenced. \nFinally, the processed data reveal protein binding intensity, \npairwise loops, and genome-wide contact maps.\n\nSee [Li et al., 2017](https://www.ncbi.nlm.nih.gov/pubmed/28358394)\n for more details on Long-Read ChIA-PET. \n\n![ChIA-PET](\nhttps://4dn-dcic-public.s3.amazonaws.com/static-pages/InfoBoxes/chia-pet.png)", "name": "item-page-headers.ExperimentType.chia-pet", "award": {"uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "status": "current", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Assay Description", "status": "released", "aliases": ["4dn-dcic-lab:chia-pet-description"], "options": {"filetype": "md", "collapsible": false, "default_open": false}, "date_created": "2019-11-20T15:19:36.383754+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2019-11-25T05:38:36.204590+00:00"}, "schema_version": "2", "@id": "/static-sections/8e2535fa-bee2-47fc-872f-91506135be5b/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "8e2535fa-bee2-47fc-872f-91506135be5b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}, "display_title": "Assay Description", "external_references": [], "content": "**ChIA-PET**\n\nChIA-PET is a method for detecting the pairwise chromatin \ninteractions mediated by a specific protein of interest, and \nLong-Read ChIA-PET is the second version of this assay (and \nis used for the ChIA-PET experiments in the 4DN data portal).\n The name \u201clong read\u201d is relative to the original ChIA-PET \nprotocol ([Fullwood et al., 2009](https://www.ncbi.nlm.nih.gov/pubmed/19890323)) \nthat used a Type IIS restriction enzyme (MmeI) to generate \n\u201cshort read\u201d (2x20 bp) paired-end tags (PET) from the \nchromatin DNA templates by proximity ligation. The key \nmodifications of Long-Read ChIA-PET from the original \nChIA-PET method are 1) the use of Tn5 transposase to cut the \nproximity-ligated chromatin DNA fragments randomly, \ngenerating longer DNA templates for sequencing analysis by \npaired-end reads (2x150 bp). Therefore, most of the PET reads\n are up to 200 bp in length by 2x200 bp paired End reading \nmodel by ILLUMINA sequencing. A minor change in the protocol \nis to use one \u201cbridge\u201d linker instead of two \u201cA-B\u201d linkers, \nfurther simplifying the protocol.  \n\nThe protocol involves dual-crosslinking the cells with \nformaldehyde and EGS to fix potential contacts between \nphysically proximal regions.  Subsequently, both the cell and \nnuclear membranes are lysed, and the fragmentation step \nfollows.  An antibody is used to pull down interactions \ninvolving a specific protein factor.  The resulting chromatin \nmaterial goes through the proximity ligation by A-tailing and \nlinker ligation.  Reverse crosslinking removes the protein, \nleaving the DNA fragments to be amplified and sequenced. \nFinally, the processed data reveal protein binding intensity, \npairwise loops, and genome-wide contact maps.\n\nSee [Li et al., 2017](https://www.ncbi.nlm.nih.gov/pubmed/28358394)\n for more details on Long-Read ChIA-PET. \n\n![ChIA-PET](\nhttps://4dn-dcic-public.s3.amazonaws.com/static-pages/InfoBoxes/chia-pet.png)", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p><strong>ChIA-PET</strong></p>\n<p>ChIA-PET is a method for detecting the pairwise chromatin \ninteractions mediated by a specific protein of interest, and \nLong-Read ChIA-PET is the second version of this assay (and \nis used for the ChIA-PET experiments in the 4DN data portal).\n The name \u201clong read\u201d is relative to the original ChIA-PET \nprotocol (<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/19890323\" rel=\"noopener noreferrer\" target=\"_blank\">Fullwood et al., 2009</a>) \nthat used a Type IIS restriction enzyme (MmeI) to generate \n\u201cshort read\u201d (2x20 bp) paired-end tags (PET) from the \nchromatin DNA templates by proximity ligation. The key \nmodifications of Long-Read ChIA-PET from the original \nChIA-PET method are 1) the use of Tn5 transposase to cut the \nproximity-ligated chromatin DNA fragments randomly, \ngenerating longer DNA templates for sequencing analysis by \npaired-end reads (2x150 bp). Therefore, most of the PET reads\n are up to 200 bp in length by 2x200 bp paired End reading \nmodel by ILLUMINA sequencing. A minor change in the protocol \nis to use one \u201cbridge\u201d linker instead of two \u201cA-B\u201d linkers, \nfurther simplifying the protocol.  </p>\n<p>The protocol involves dual-crosslinking the cells with \nformaldehyde and EGS to fix potential contacts between \nphysically proximal regions.  Subsequently, both the cell and \nnuclear membranes are lysed, and the fragmentation step \nfollows.  An antibody is used to pull down interactions \ninvolving a specific protein factor.  The resulting chromatin \nmaterial goes through the proximity ligation by A-tailing and \nlinker ligation.  Reverse crosslinking removes the protein, \nleaving the DNA fragments to be amplified and sequenced. \nFinally, the processed data reveal protein binding intensity, \npairwise loops, and genome-wide contact maps.</p>\n<p>See <a href=\"https://www.ncbi.nlm.nih.gov/pubmed/28358394\" rel=\"noopener noreferrer\" target=\"_blank\">Li et al., 2017</a>\n for more details on Long-Read ChIA-PET. </p>\n<p><img alt=\"ChIA-PET\" src=\"https://4dn-dcic-public.s3.amazonaws.com/static-pages/InfoBoxes/chia-pet.png\"/></p></div>"}], "project_release": "2019-02-21", "experiments_in_set": [{"files": [{"file_type_detailed": "reads (fastq)", "file_size": 903975256, "uuid": "610f479f-76e3-4f32-85a9-26d8d4c447c5", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/files/610f479f-76e3-4f32-85a9-26d8d4c447c5/4DNFI97YRQDN.fastq.gz", "file_type": "reads", "upload_key": "610f479f-76e3-4f32-85a9-26d8d4c447c5/4DNFI97YRQDN.fastq.gz", "@id": "/files-fastq/4DNFI97YRQDN/", 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