{"lab": {"title": "Siyuan Wang, YALE", "@type": ["Lab", "Item"], "@id": "/labs/siyuan-wang-lab/", "uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "correspondence": [{"contact_email": "c2l5dWFuLndhbmdAeWFsZS5lZHU=", "@id": "/users/774c29b8-db1e-48bc-9669-a3e380f435c2/", "display_title": "Siyuan Wang"}], "display_title": "Siyuan Wang, YALE", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.7f49b420-d2ae-4de4-820a-21403dc0749f"]}}, "tags": ["skip_processing"], "award": {"display_title": "GENOME ARCHITECTURE IN HUMAN GERMINAL CENTER B CELL DEVELOPMENT, MALIGNANCY, AND SOMATIC HYPERMUTATION", "@type": ["Award", "Item"], "name": "1U01CA260701-01", "uuid": "f959fce7-bd94-4a8d-961d-8c72a4eaa1ad", "description": "OFHHD: During the humoral immune response, somatic hypermutation (SHM) introduces point mutations in rearranged immunoglobulin (Ig) genes of activated germinal center (GC) B cells. SHM is essential for the fine-tuning of antibody affinity, the generation of B cells expressing high-affinity antibody, and the efficacy of many vaccines. Mistargeted SHM activities can lead to mutations and chromosomal translocations that contribute to the development of B cell lymphoma. Recent studies suggest that the three-dimensional (3D) organization of the genome regulates SHM targeting and mistargeting. However, it is largely unknown how the genome is spatially organized across multiple length scales in GC B cell development and lymphoma, and how 3D genome architecture mechanistically affects the targeting and mistargeting of SHM. Conventional approaches cannot address these questions in the primary GC tissue environment due to technical limitations. Here, we propose to apply a new method recently developed by our team, termed Multiplexed Imaging of Nucleome Architectures (MINA), to primary human tonsil tissue samples and malignant GC-derived human B cell lymphomas. We will investigate and test the association between SHM susceptibility and a variety of 3D nucleome architectures, including topologically associating domain (TAD) architecture, phase separation, and nuclear positioning of genomic regions relative to nuclear lamina, nucleoli, and nuclear pores. Through targeted genomic perturbations in human B cell lymphomas, we will test specific hypotheses linking SHM targeting elements to elevated chromatin looping interactions, TAD phase separation, nuclear pore proximity, and mutation vulnerability. Our study will significantly advance our understanding of the role of 3D genome architecture and nuclear organization in GC B cells undergoing SHM in both the developmental and tumorigenesis contexts. We expect this study to establish a new research paradigm and transform 3D nucleome investigations in immunobiology.", "center_title": "OFHHD - Schatz", "@id": "/awards/1U01CA260701-01/", "status": "current", "project": "4DN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "study": "Hi-C in LUAD", "badges": [{"badge": {"display_title": "Inconsistent Replicate Info", "description": "The experimental replicates belonging to this Experiment Set differ in some specific metadata fields", "uuid": "a4df9ff7-fe85-4672-86ac-7c38b5d9c853", "badge_classification": "Warning", "title": "Inconsistent Replicate Info", "warning": "Inconsistent Replicate Info", "status": "released", "@type": ["Badge", "Item"], "@id": "/badges/inconsistent-replicate-info/", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "messages": ["Inconsistent replicate information in biosource: lung - 4DNSR4FIZXGS, lung - 4DNSRNRUOWTJ"]}], "status": "released", "aliases": ["siyuan-wang-lab:expset_hic_LUAD_k_MADM"], "accession": "4DNESRNRHHPX", "condition": "LUAD (GFP+)", "description": "Hi-C in GFP+ expressing (green) homozygous mutant (Trp53 -/-)  LUAD cells from K-MADM-Trp53 mouse", "study_group": "Disrupted or Atypical Cells", "date_created": "2025-05-27T17:47:11.903455+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Hi-C in lung tissue", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-06-23T19:12:00.641925+00:00"}, "public_release": "2025-06-12", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"accession": "4DNEX8N81INM", "@id": "/experiments-hi-c/4DNEX8N81INM/", "@type": ["ExperimentHiC", "Experiment", "Item"], "status": "released", "display_title": "in situ Hi-C on lung with Arima - F1, A2, F3, F4 - 4DNEX8N81INM", "uuid": "19d88a50-bdb4-46b3-8eb3-ca7f9b4facd3", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"accession": "4DNEXPNWNXDD", "@id": "/experiments-hi-c/4DNEXPNWNXDD/", "@type": ["ExperimentHiC", "Experiment", "Item"], "status": "released", "display_title": "in situ Hi-C on lung with Arima - F1, A2, F3, F4 - 4DNEXPNWNXDD", "uuid": "cf51e304-dfac-4297-b6ad-5b93a2dca688", "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", "status": "current", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "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": {"@id": "/awards/1U01CA200059-01/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "status": "current", "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>"}], "project_release": "2025-06-12", "experiments_in_set": [{"uuid": "19d88a50-bdb4-46b3-8eb3-ca7f9b4facd3", "@type": ["ExperimentHiC", "Experiment", "Item"], "status": "released", "accession": "4DNEX8N81INM", "@id": "/experiments-hi-c/4DNEX8N81INM/", "display_title": "in situ Hi-C on lung with Arima - F1, A2, F3, F4 - 4DNEX8N81INM", "files": [{"accession": "4DNFI9TD1GBU", "display_title": "4DNFI9TD1GBU.fastq.gz", "paired_end": "1", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/files/8600092b-8c77-45a8-a1d0-4e642c8d1efa/4DNFI9TD1GBU.fastq.gz", "upload_key": "8600092b-8c77-45a8-a1d0-4e642c8d1efa/4DNFI9TD1GBU.fastq.gz", "file_type": "reads", "@type": ["FileFastq", "File", "Item"], "href": "/files-fastq/4DNFI9TD1GBU/@@download/4DNFI9TD1GBU.fastq.gz", "file_type_detailed": "reads (fastq)", "md5sum": "d73c7ab33c5980eb651e45b8cc654b34", "uuid": "8600092b-8c77-45a8-a1d0-4e642c8d1efa", "@id": "/files-fastq/4DNFI9TD1GBU/", "file_size": 1034378182, "status": "released", "file_classification": "raw file", "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFI6MGNIVG", "status": "released", "@type": ["FileFastq", "File", "Item"], "file_type": "reads", "display_title": "4DNFI6MGNIVG.fastq.gz", "@id": "/files-fastq/4DNFI6MGNIVG/", "uuid": "127f7971-f058-4764-adda-8efe9d99b6d6", "paired_end": "2", "file_type_detailed": "reads (fastq)", "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "display_title": "fastq", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@id": "/file-formats/fastq/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "file_format": {"uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "file_format": "fastq", "@type": ["FileFormat", "Item"], "@id": "/file-formats/fastq/", "status": "released", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "lab": {"display_title": "Siyuan Wang, YALE", "uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "status": "current", "@type": ["Lab", "Item"], "name": "siyuan-wang-lab", "@id": "/labs/siyuan-wang-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.7f49b420-d2ae-4de4-820a-21403dc0749f"]}}, "quality_metric": {"display_title": "QualityMetricFastqc from 2025-05-28", "@id": "/quality-metrics-fastqc/38f43678-aec8-4672-b2a5-80492d3558f7/", "overall_quality_status": "PASS", "Sequence length": "150", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFI9TD1GBU/fastqc_report.html", "status": "released", "Total Sequences": 16527555, "uuid": "38f43678-aec8-4672-b2a5-80492d3558f7", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "external_references": [], "track_and_facet_info": {"experimental_lab": "Siyuan Wang, YALE", "experiment_type": "in situ Hi-C", "experiment_bucket": "raw file", "assay_info": "Arima - 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Our data reveal stereotypical, non-monotonic, and  stage-specific alterations in 3D genome folding heterogeneity, compaction, and  compartmentalization as cancers progress from normal to preinvasive and  ultimately to invasive tumors, discovering a potential structural bottleneck in  early tumor progression. Remarkably, 3D genome architectures distinguish  histologic cancer states in single cells, despite considerable cell-to-cell  heterogeneity. Gene-level analyses of evolutionary changes in 3D genome  compartmentalization not only showed compartment-associated genes are more  homogeneously regulated, but also elucidated prognostic and dependency genes in  lung adenocarcinoma and a previously unappreciated role for polycomb-group  protein Rnf2 in 3D genome regulation. Our results demonstrate the utility of  mapping the single-cell cancer 3D genome in tissues and illuminate its potential  to identify new diagnostic, prognostic, and therapeutic biomarkers in cancer.", "@id": "/publications/e83173f7-95e4-40ad-9748-e13b2a518fc6/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"display_title": "Liu M et al. 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Our data reveal stereotypical, non-monotonic, and  stage-specific alterations in 3D genome folding heterogeneity, compaction, and  compartmentalization as cancers progress from normal to preinvasive and  ultimately to invasive tumors, discovering a potential structural bottleneck in  early tumor progression. Remarkably, 3D genome architectures distinguish  histologic cancer states in single cells, despite considerable cell-to-cell  heterogeneity. Gene-level analyses of evolutionary changes in 3D genome  compartmentalization not only showed compartment-associated genes are more  homogeneously regulated, but also elucidated prognostic and dependency genes in  lung adenocarcinoma and a previously unappreciated role for polycomb-group  protein Rnf2 in 3D genome regulation. Our results demonstrate the utility of  mapping the single-cell cancer 3D genome in tissues and illuminate its potential  to identify new diagnostic, prognostic, and therapeutic biomarkers in cancer.", "date_published": "2024-09-09", "@id": "/publications/e83173f7-95e4-40ad-9748-e13b2a518fc6/", "ID": "doi:10.1101/2023.07.23.550157", "@type": ["Publication", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/experiment-set-replicates/4DNESRNRHHPX/", "embedded_path": "badges", "item": {"messages": ["Inconsistent replicate information in biosource: lung - 4DNSR4FIZXGS, lung - 4DNSRNRUOWTJ"], "badge": {"commendation": null, "warning": "Inconsistent Replicate Info", "uuid": "a4df9ff7-fe85-4672-86ac-7c38b5d9c853", "@id": "/badges/inconsistent-replicate-info/", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "description": "The experimental replicates belonging to this Experiment Set differ in some specific metadata fields"}}}]}, "validation-errors": []}