{"lab": {"status": "current", "title": "Rafael Casellas, NIH", "display_title": "Rafael Casellas, NIH", "correspondence": [{"contact_email": "Y2FzZWxsYXJAbWFpbC5uaWguZ292", "@id": "/users/68b09572-0c3e-48c7-90a9-7bad21d6bac1/", "display_title": "Rafael Casellas"}], "uuid": "ce54a7f7-af8a-4505-8327-e430634f494b", "@type": ["Lab", "Item"], "@id": "/labs/rafael-casellas-lab/", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.ce54a7f7-af8a-4505-8327-e430634f494b"]}}, "award": {"center": "External", "@type": ["Award", "Item"], "@id": "/awards/external-award/", "display_title": "EXTERNAL AWARD", "uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "description": "Funding source is from outside 4DN.", "name": "external-award", "project": "External", "center_title": "External", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "study": "Cohesin Protein Function", "status": "released", "aliases": ["4dn-dcic-lab:HCT-116_HCT-116-RAD21-mAC_olig_30_minute_in_situ_Hi-C"], "dbxrefs": ["GEO:GSE98119"], "accession": "4DNESJ5Y5ZN8", "condition": "no ATP", "description": "in situ Hi-C on HCT-116 (HCT-116-RAD21-mAC), treated with oligomycin (30 minute) to deplete ATP", "study_group": "Disrupted or Atypical Cells", "date_created": "2018-11-27T18:26:51.767854+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Hi-C on RAD21-AID tagged HCT-116", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-07-16T15:55:59.049925+00:00"}, "public_release": "2019-11-25", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"@id": "/experiments-hi-c/4DNEX4WKN1IH/", "uuid": "97902071-17c5-46ab-9a12-3f2a487afef6", "status": "released", "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEX4WKN1IH", "@type": ["ExperimentHiC", "Experiment", "Item"], "accession": "4DNEX4WKN1IH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXTINTVGR/", "uuid": "c124d9d9-e1a8-4f6e-8809-00ec1a849f8e", "status": "released", "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEXTINTVGR", "@type": ["ExperimentHiC", "Experiment", "Item"], "accession": "4DNEXTINTVGR", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_content": [{"content": {"@id": "/higlass-view-configs/efcd7a4c-69f5-4c9a-9272-467157bb2f98/", "status": "released", "display_title": "4DNESJ5Y5ZN8 - Processed files", "award": {"@type": ["Award", "Item"], "display_title": "EXTERNAL AWARD", "status": "current", "@id": "/awards/external-award/", "uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "contributing_labs": [], "title": "4DNESJ5Y5ZN8 - Processed files", "lab": {"display_title": "Rafael Casellas, NIH", "@id": "/labs/rafael-casellas-lab/", "@type": ["Lab", "Item"], "status": "current", "uuid": "ce54a7f7-af8a-4505-8327-e430634f494b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.ce54a7f7-af8a-4505-8327-e430634f494b"]}}, "@type": ["HiglassViewConfig", "UserContent", "Item"], "name": "efcd7a4c-69f5-4c9a-9272-467157bb2f98", "uuid": "efcd7a4c-69f5-4c9a-9272-467157bb2f98", "description": "4DNESJ5Y5ZN8 (in situ Hi-C on HCT-116 (HCT-116-RAD21-mAC), treated with oligomycin (30 minute) to deplete ATP): 4DNFITRU4CYZ, 4DNFIO6VYTYE", "filetype": "HiglassViewConfig", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267307e3a"]}}, "location": "tab:processed-files", "description": "auto_generated_higlass_view_config"}], "static_headers": [{"lab": {"display_title": "4DN DCIC, HMS", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "<b>In Situ Hi-C</b>\n\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. 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>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\">Rao et al., 2014</a> for more details.\n</p>\n\n<div>\n<img style=\"width: 600px;max-width:100%;\" src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\"/>\n  <br/><br/>\n  <em>Image source: Rao et al., 2014, Figure 1A</em>\n</div>", "name": "item-page-headers.ExperimentType.insituhic", "award": {"@type": ["Award", "Item"], "status": "current", "@id": "/awards/1U01CA200059-01/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Assay Description", "status": "released", "aliases": ["4dn-dcic-lab:experiment_infobox_hic"], "options": {"filetype": "html", "collapsible": false, "default_open": false, "convert_ext_links": true}, "date_created": "2018-09-07T18:19:43.777198+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-11-09T14:48:01.220007+00:00"}, "schema_version": "2", "@id": "/static-sections/298554ad-20e2-4449-a752-ac190123dab7/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "298554ad-20e2-4449-a752-ac190123dab7", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.56c9c683-bb11-471b-b590-c656f7dc03c1"]}, "display_title": "Assay Description", "external_references": [], "content": "<b>In Situ Hi-C</b>\n\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. 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>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\">Rao et al., 2014</a> for more details.\n</p>\n\n<div>\n<img style=\"width: 600px;max-width:100%;\" src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\"/>\n  <br/><br/>\n  <em>Image source: Rao et al., 2014, Figure 1A</em>\n</div>", "filetype": "html", "content_as_html": "<div class=\"html-container\"><b>In Situ Hi-C</b>\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. 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>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\" rel=\"noopener noreferrer\" target=\"_blank\">Rao et al., 2014</a> for more details.\n</p>\n<div>\n<img src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\" style=\"width: 600px;max-width:100%;\"/>\n<br/><br/>\n<em>Image source: Rao et al., 2014, Figure 1A</em>\n</div></div>"}, {"lab": {"display_title": "4DN DCIC, HMS", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "Some annotated bam and pairs files generated in this Experiment Set may contain distinct reads that share the same identifier. 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This was caused by merging fastq files with integer identifiers (eg. @1, @2) during processing.", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p>Some annotated bam and pairs files generated in this Experiment Set may contain distinct reads that share the same identifier. 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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.  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(2018)", "title": "The Energetics and Physiological Impact of Cohesin Extrusion.", "@type": ["Publication", "Item"], "uuid": "89ec268b-d05c-4841-8806-a49fb0d99e78", "display_title": "Vian L et al. (2018) PMID:29706548", "ID": "PMID:29706548", "date_published": "2018-04-26", "status": "current", "authors": ["Vian L", "Pekowska A", "Rao SSP", "Kieffer-Kwon KR", "Jung S", "Baranello L", "Huang SC", "El Khattabi L", "Dose M", "Pruett N", "Sanborn AL", "Canela A", "Maman Y", "Oksanen A", "Resch W", "Li X", "Lee B", "Kovalchuk AL", "Tang Z", "Nelson S", "Di Pierro M", "Cheng RR", "Machol I", "St Hilaire BG", "Durand NC", "Shamim MS", "Stamenova EK", "Onuchic JN", "Ruan Y", "Nussenzweig A", "Levens D", "Aiden EL", "Casellas R"], "@id": "/publications/89ec268b-d05c-4841-8806-a49fb0d99e78/", "url": "https://www.ncbi.nlm.nih.gov/pubmed/29706548", "abstract": "Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in  vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for  hours without energy input. Strikingly, without ATP, we observe the emergence of  hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural \"stripes,\" where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.", "journal": "Cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"authors": ["Vian L", "Pekowska A", "Rao SSP", "Kieffer-Kwon KR", "Jung S", "Baranello L", "Huang SC", "El Khattabi L", "Dose M", "Pruett N", "Sanborn AL", "Canela A", "Maman Y", "Oksanen A", "Resch W", "Li X", "Lee B", "Kovalchuk AL", "Tang Z", "Nelson S", "Di Pierro M", "Cheng RR", "Machol I", "St Hilaire BG", "Durand NC", "Shamim MS", "Stamenova EK", "Onuchic JN", "Ruan Y", "Nussenzweig A", "Levens D", "Aiden EL", "Casellas R"], "date_published": "2018-04-26", "@type": ["Publication", "Item"], "title": "The Energetics and Physiological Impact of Cohesin Extrusion.", "display_title": "Vian L et al. (2018) PMID:29706548", "ID": "PMID:29706548", "status": "current", "uuid": "89ec268b-d05c-4841-8806-a49fb0d99e78", "@id": "/publications/89ec268b-d05c-4841-8806-a49fb0d99e78/", "journal": "Cell", "abstract": "Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in  vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for  hours without energy input. Strikingly, without ATP, we observe the emergence of  hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural \"stripes,\" where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSP7UWF2E/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}, {"parent": "/biosamples/4DNBSLU9O4R6/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}