{"lab": {"@id": "/labs/danwei-huangfu-lab/", "title": "Danwei Huangfu, MSKCC", "status": "current", "correspondence": [{"contact_email": "aHVhbmdmdWRAbXNrY2Mub3Jn", "@id": "/users/b9ddcafc-fc2d-401d-98a6-dd1cb39b2982/", "display_title": "Danwei Huangfu"}], "uuid": "bd4a15cf-e3f4-4938-933e-787883a48d7c", "@type": ["Lab", "Item"], "display_title": "Danwei Huangfu, MSKCC", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.bd4a15cf-e3f4-4938-933e-787883a48d7c"]}}, "award": {"display_title": "DISCOVERY OF DIABETES-RELEVANT BETA CELL ENHANCERS THROUGH 4D ENHANCER MAPPING, INTEGRATIVE ANALYSIS, AND LARGE-SCALE CRISPRI PERTURBATION SCREENS", "name": "1U01DK128852-01", "status": "current", "@id": "/awards/1U01DK128852-01/", "uuid": "8432a44c-4da7-446b-9080-f4fae299ebd6", "project": "4DN", "@type": ["Award", "Item"], "description": "OFHHD: Enhancers are essential regulatory elements that together with transcription factors (TFs) instruct cell- type specific transcriptional programs during development, tissue homeostasis and regeneration. Initiatives such as the ENCODE project, revealed tens of thousands putative enhancers based on linear proximity, using criteria like chromatin accessibility, TF binding, and histone modifications such as H3K27ac. However, a main challenge of uncovering functional enhancers and assigning them to target genes lies in the complexity of the 3D chromatin organization, which can influence enhancer specificity and activity. Using an advanced chromosome conformation capture assay, we recently captured the dynamic rewiring of 3D enhancer networks during mouse somatic cell reprogramming and discovered multi-connected enhancers that we named \u201c3D enhancer hubs\u201d. Here we extend the 3D mapping approach to human primary islets, and compare islets from healthy and type 2 diabetes (T2D) donors to assemble a 4D atlas to capture the rewiring of 3D enhancer network in disease progression. At the same time, we plan to compare the enhancer network in adult islets to earlier stages of development by using human pluripotent stem cells (hPSCs) to generate early \u03b2 cells and their developmental precursors. Utilizing these 4D genomic data, we will computationally nominate core \u03b2-cell specific enhancers relevant to \u03b2 cell development, function, and T2D, and then interrogate these putative enhancers through large-scale CRISPRi mediated perturbation screens using hPSC-\u03b2 cells. Enhancers identified from the screening effort will be further validated in an established human \u03b2 cell line and primary human islet \u03b2 cells. This proposal addresses a critical gap in the 4DN initiative, that is how to translate 3D genomics data into functional data with respect to gene expression in the context of human health. Successful completion of our aims will establish a paradigm for the discovery and interrogation of functional enhancers that instruct transcriptional programs specific to a cell type of interest, reveal unique insights into their mechanisms of action, and identify enhancers with relevance to human development and disease. For instance, uncovering functional enhancers could assist the identification of noncoding causal variants identified in genome-wide association studies.", "center_title": "OFHHD - Huangfu", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "files": [{"file_type": "reads", "href": "/files-fastq/4DNFI9AG96CB/@@download/4DNFI9AG96CB.fastq.gz", "file_size": 7195513925, "status": "released", "accession": "4DNFI9AG96CB", "@type": ["FileFastq", "File", "Item"], "upload_key": "a5b3935a-c220-422a-8eda-bcbff2433aaa/4DNFI9AG96CB.fastq.gz", "uuid": "a5b3935a-c220-422a-8eda-bcbff2433aaa", "@id": "/files-fastq/4DNFI9AG96CB/", "file_classification": "raw file", "paired_end": "1", "file_type_detailed": "reads (fastq)", "display_title": "4DNFI9AG96CB.fastq.gz", "file_format": {"file_format": "fastq", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"uuid": "ebffe254-f32e-492e-b926-0fac0835091d", "status": "released", "overall_quality_status": "PASS", "Sequence length": "100", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFI9AG96CB/fastqc_report.html", "Total Sequences": 124120580, "display_title": "QualityMetricFastqc from 2023-06-01", "@id": "/quality-metrics-fastqc/ebffe254-f32e-492e-b926-0fac0835091d/", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIYQY94PS", "uuid": "32d8e2f8-4242-45fe-83c1-3d677255ecc5", "status": "released", "display_title": "4DNFIYQY94PS.fastq.gz", "paired_end": "2", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIYQY94PS/", "file_type_detailed": "reads (fastq)", "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": []}, {"file_type": "reads", "href": "/files-fastq/4DNFIYQY94PS/@@download/4DNFIYQY94PS.fastq.gz", "file_size": 7850161472, "status": "released", "accession": "4DNFIYQY94PS", "@type": ["FileFastq", "File", "Item"], "upload_key": "32d8e2f8-4242-45fe-83c1-3d677255ecc5/4DNFIYQY94PS.fastq.gz", "uuid": "32d8e2f8-4242-45fe-83c1-3d677255ecc5", "@id": "/files-fastq/4DNFIYQY94PS/", "file_classification": "raw file", "paired_end": "2", "file_type_detailed": "reads (fastq)", "display_title": "4DNFIYQY94PS.fastq.gz", "file_format": {"file_format": "fastq", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"uuid": "55e63d64-70af-4309-a961-d4fe1bed1811", "status": "released", "overall_quality_status": "PASS", "Sequence length": "100", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIYQY94PS/fastqc_report.html", "Total Sequences": 124120580, "display_title": "QualityMetricFastqc from 2023-06-01", "@id": "/quality-metrics-fastqc/55e63d64-70af-4309-a961-d4fe1bed1811/", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFI9AG96CB", "uuid": "a5b3935a-c220-422a-8eda-bcbff2433aaa", "status": "released", "display_title": "4DNFI9AG96CB.fastq.gz", "paired_end": "1", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFI9AG96CB/", "file_type_detailed": "reads (fastq)", "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": []}, {"file_type": "reads", "href": "/files-fastq/4DNFII8QMLYK/@@download/4DNFII8QMLYK.fastq.gz", "file_size": 13065406021, "status": "released", "accession": "4DNFII8QMLYK", "@type": ["FileFastq", "File", "Item"], "upload_key": "ebfad9c6-85b0-4952-bd65-7c65903de526/4DNFII8QMLYK.fastq.gz", "uuid": "ebfad9c6-85b0-4952-bd65-7c65903de526", "@id": "/files-fastq/4DNFII8QMLYK/", "file_classification": "raw file", "paired_end": "1", "file_type_detailed": "reads (fastq)", "display_title": "4DNFII8QMLYK.fastq.gz", "file_format": {"file_format": "fastq", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"uuid": "30154581-d927-413a-a9a8-15a575adc1aa", "status": "released", "overall_quality_status": "PASS", "Sequence length": "100", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFII8QMLYK/fastqc_report.html", "Total Sequences": 216834998, "display_title": "QualityMetricFastqc from 2023-06-01", "@id": "/quality-metrics-fastqc/30154581-d927-413a-a9a8-15a575adc1aa/", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFI46MSH3U", "uuid": "14cfcc13-15ec-49f7-a2fc-db5d85dabdae", "status": "released", "display_title": "4DNFI46MSH3U.fastq.gz", "paired_end": "2", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFI46MSH3U/", "file_type_detailed": "reads (fastq)", "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": []}, {"file_type": "reads", "href": "/files-fastq/4DNFI46MSH3U/@@download/4DNFI46MSH3U.fastq.gz", "file_size": 14841110723, "status": "released", "accession": "4DNFI46MSH3U", "@type": ["FileFastq", "File", "Item"], "upload_key": "14cfcc13-15ec-49f7-a2fc-db5d85dabdae/4DNFI46MSH3U.fastq.gz", "uuid": "14cfcc13-15ec-49f7-a2fc-db5d85dabdae", "@id": "/files-fastq/4DNFI46MSH3U/", "file_classification": "raw file", "paired_end": "2", "file_type_detailed": "reads (fastq)", "display_title": "4DNFI46MSH3U.fastq.gz", "file_format": {"file_format": "fastq", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"uuid": "b8a95c1f-9cbc-465c-8144-c8875ae02ff0", "status": "released", "overall_quality_status": "PASS", "Sequence length": "100", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFI46MSH3U/fastqc_report.html", "Total Sequences": 216834998, "display_title": "QualityMetricFastqc from 2023-06-01", "@id": "/quality-metrics-fastqc/b8a95c1f-9cbc-465c-8144-c8875ae02ff0/", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFII8QMLYK", "uuid": "ebfad9c6-85b0-4952-bd65-7c65903de526", "status": "released", "display_title": "4DNFII8QMLYK.fastq.gz", "paired_end": "1", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFII8QMLYK/", "file_type_detailed": "reads (fastq)", "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": []}], "status": "released", "aliases": ["danwei-huang-lab:experiment_hi-c_sox17-eGFP_idCAS9-KRAB_HUES8_DE_B1_T1"], "protocol": {"@type": ["Protocol", "Item"], "display_title": "Arima Hi-C Protocol v01", "uuid": "1686012d-09fd-44e5-b01b-14789205a091", "status": "released", "@id": "/protocols/1686012d-09fd-44e5-b01b-14789205a091/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNEX143ONJ6", "biosample": {"biosample_type": "in vitro differentiated cells", "@id": "/biosamples/4DNBSN9IPIX5/", "@type": ["Biosample", "Item"], "accession": "4DNBSN9IPIX5", "treatments_summary": "None", "display_title": "4DNBSN9IPIX5", "uuid": "813477bc-011c-4fd3-894e-013ae24ce10f", "status": "released", "modifications_summary": "None", "biosource_summary": "SOX17-eGFP idCAS9-KRAB HUES8 differentiated to definitive endoderm", "biosource": [{"lab": {"status": "current", "display_title": "4DN DCIC, HMS", "@type": ["Lab", "Item"], "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "award": {"status": "current", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE II", "@id": "/awards/2U01CA200059-06/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "tissue": {"@type": ["OntologyTerm", "Item"], "synonyms": ["animal stem cell"], "uuid": "082f5be3-3617-4d3e-9ee9-78df53a71802", "term_name": "stem cell", "display_title": "stem cell", "status": "released", "term_id": "CL:0000034", "preferred_name": "stem cell", "@id": "/ontology-terms/CL:0000034/", "slim_terms": [{"@id": "/ontology-terms/GO:0005623/", "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "display_title": "cell", "status": "current", "@type": ["OntologyTerm", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@id": "/ontology-terms/CL:0000000/", "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "display_title": "cell", "status": "released", "@type": ["OntologyTerm", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "aliases": ["4dn-dcic-lab:SOX17-eGFP_idCAS9_KRAB_HUES8"], "accession": "4DNSRNFGSF8Z", "cell_line": {"@type": ["OntologyTerm", "Item"], "preferred_name": "HUES8", "status": "released", "term_name": "HUES8", "slim_terms": [{"uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "status": "current", "@id": "/ontology-terms/GO:0005623/", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "status": "released", "@id": "/ontology-terms/CL:0000000/", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "uuid": "02f9ae7e-c6cb-4e6b-9702-11e758dd5992", "display_title": "HUES8", "term_id": "EFO:0007093", "@id": "/ontology-terms/EFO:0007093/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "individual": {"protected_data": false, "display_title": "4DNINY4RLELC", "uuid": "e5c8280b-229d-4acb-97c2-e6b09a430614", "@type": ["IndividualHuman", "Individual", "Item"], "status": "released", "@id": "/individuals-human/4DNINY4RLELC/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "description": "HUES8 embryonic stem cell line engineered with inducible dead CAS9-KRAB  and SOX17-eGFP", "date_created": "2022-12-15T21:18:35.114102+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-06-09T14:49:29.227131+00:00"}, "biosource_type": "stem cell derived cell line", "cell_line_tier": "Unclassified", "public_release": "2023-06-09", "schema_version": "2", "project_release": "2023-06-09", "contributing_labs": [{"display_title": "Danwei Huangfu, MSKCC", "status": "current", "uuid": "bd4a15cf-e3f4-4938-933e-787883a48d7c", "@type": ["Lab", "Item"], "@id": "/labs/danwei-huangfu-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.bd4a15cf-e3f4-4938-933e-787883a48d7c"]}}, {"display_title": "Effie Apostolou, CORNELL", "status": "current", "uuid": "25604a5f-772b-43e2-a004-136ce41d0090", "@type": ["Lab", "Item"], "@id": "/labs/effie-apostolou-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.25604a5f-772b-43e2-a004-136ce41d0090"]}}, {"display_title": "Christina Leslie, MSKCC", "status": "current", "uuid": "b533abb2-66ea-4f89-b34f-22ba1954b38a", "@type": ["Lab", "Item"], "@id": "/labs/christina-leslie-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b533abb2-66ea-4f89-b34f-22ba1954b38a"]}}], "override_biosource_name": "SOX17-eGFP idCAS9-KRAB HUES8", "@id": "/biosources/4DNSRNFGSF8Z/", "@type": ["Biosource", "Item"], "uuid": "7353cd9a-1a70-47f2-821f-eafd51b1ac5c", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "SOX17-eGFP idCAS9-KRAB HUES8 - 4DNSRNFGSF8Z", "external_references": [], "biosource_name": "SOX17-eGFP idCAS9-KRAB HUES8", "biosource_category": ["Human stem cell"], "organism": {"uuid": "7745b647-ff15-4ff3-9ced-b897d4e2983c", "@type": ["Organism", "Item"], "@id": "/organisms/9606/", "display_title": "H. sapiens", "name": "human", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "badges": [{"messages": ["Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing culture_duration", "Biosample missing morphology_image"], "badge": {"description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group.", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "status": "released", "title": "Biosample Metadata Incomplete", "@type": ["Badge", "Item"], "badge_icon": "/static/img/badges/biosample-icon.svg", "@id": "/badges/biosample-metadata-incomplete/", "badge_classification": "Warning", "display_title": "Biosample Metadata Incomplete", "warning": "Biosample Metadata Incomplete", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "sop_mapping": {"has_sop": "No"}, "date_created": "2023-05-31T15:11:27.031654+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-06-09T14:47:56.952423+00:00"}, "ligation_time": 15.0, "biotin_removed": "No", "digestion_time": 30.0, "public_release": "2023-06-09", "schema_version": "2", "experiment_type": {"assay_subclass_short": "Hi-C", "display_title": "in situ Hi-C", "@id": "/experiment-types/in-situ-hi-c/", "status": "released", "title": "in situ Hi-C", "@type": ["ExperimentType", "Item"], "uuid": "a2920a38-cdba-4ff0-b4f0-c6bb53257747", "experiment_category": "Sequencing", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "ligation_volume": 0.082, "processed_files": [{"file_type": "alignments", "@id": "/files-processed/4DNFIH6D46DE/", "@type": ["FileProcessed", "File", "Item"], "file_type_detailed": "alignments (bam)", "uuid": "60c6a06a-1d84-43bf-95da-98aaf428f357", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/60c6a06a-1d84-43bf-95da-98aaf428f357/4DNFIH6D46DE.bam", "status": "released", "file_classification": "processed file", "file_format": {"uuid": "d13d06cf-218e-4f61-aaf0-91f226248b3c", "status": "released", "@id": "/file-formats/bam/", "@type": ["FileFormat", "Item"], "file_format": "bam", "display_title": "bam", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "href": "/files-processed/4DNFIH6D46DE/@@download/4DNFIH6D46DE.bam", "display_title": "4DNFIH6D46DE.bam", "accession": "4DNFIH6D46DE", "file_size": 63365676062, "upload_key": "60c6a06a-1d84-43bf-95da-98aaf428f357/4DNFIH6D46DE.bam", "quality_metric": {"status": "released", "@id": "/quality-metrics-bamqc/1bb202b7-af6c-4d69-b2fa-1d8269da8ce1/", "display_title": "QualityMetricBamqc from 2023-06-02", "uuid": "1bb202b7-af6c-4d69-b2fa-1d8269da8ce1", "@type": ["QualityMetricBamqc", "QualityMetric", "Item"], "overall_quality_status": "PASS", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "quality_metric_summary": [{"title": "Total Reads", "value": "340955578", "numberType": "integer"}, {"title": "Unmapped Reads", "value": "6.808", "tooltip": "Percent of total reads (=23.21m)", "numberType": "percent"}, {"title": "Multimapped Reads", "value": "10.075", "tooltip": "Percent of total reads (=34.35m)", "numberType": "percent"}, {"title": "Duplicate Reads", "value": "3.907", "tooltip": "Percent of total reads (=13.32m)", "numberType": "percent"}, {"title": "Walks", "value": "7.4", "tooltip": "Percent of total reads (=25.23m)", "numberType": "percent"}, {"title": "Minor Contigs", "value": "0.172", "tooltip": "Percent of total reads (=0.58m)", "numberType": "percent"}]}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "external_references": [], "track_and_facet_info": {"experimental_lab": "Danwei Huangfu, MSKCC", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "Arima - A1, A2", "dataset": "in situ Hi-C on hESCs differentiated toward pancreatic cells", "condition": "definitive endoderm - HUES8", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "SOX17-eGFP idCAS9-KRAB HUES8 differentiated to definitive endoderm", "lab_name": "4DN DCIC, HMS"}}, {"file_type": "contact list-replicate", "@id": "/files-processed/4DNFIL7OOS69/", "@type": ["FileProcessed", "File", "Item"], "file_type_detailed": "contact list-replicate (pairs)", "uuid": "a4714a03-e874-42bd-aeb6-3eded4f60a89", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/a4714a03-e874-42bd-aeb6-3eded4f60a89/4DNFIL7OOS69.pairs.gz", "status": "released", "file_classification": "processed file", "file_format": {"uuid": "d13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "@id": "/file-formats/pairs/", "@type": ["FileFormat", "Item"], "file_format": "pairs", "display_title": "pairs", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "href": "/files-processed/4DNFIL7OOS69/@@download/4DNFIL7OOS69.pairs.gz", "display_title": "4DNFIL7OOS69.pairs.gz", "accession": "4DNFIL7OOS69", "file_size": 5047773836, "upload_key": "a4714a03-e874-42bd-aeb6-3eded4f60a89/4DNFIL7OOS69.pairs.gz", "quality_metric": {"status": "released", "@id": "/quality-metrics-pairsqc/47b98e83-6860-415a-825e-9fc0f5a52440/", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIL7OOS69/pairsqc_report.html", "display_title": "QualityMetricPairsqc from 2023-06-02", "uuid": "47b98e83-6860-415a-825e-9fc0f5a52440", "Total reads": 244836368, "@type": ["QualityMetricPairsqc", "QualityMetric", "Item"], "overall_quality_status": "PASS", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "quality_metric_summary": [{"title": "Filtered Reads", "value": "244836368", "numberType": "integer"}, {"title": "Cis reads (>20kb)", "value": "51.242", "tooltip": "Percent of filtered reads (=125.46m)", "numberType": "percent"}, {"title": "Short cis reads", "value": "26.94", "tooltip": "Percent of filtered reads (=65.96m)", "numberType": "percent"}, {"title": "Trans Reads", "value": "21.818", "tooltip": "Percent of filtered reads (=53.42m)", "numberType": "percent"}]}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "external_references": [], "track_and_facet_info": {"experimental_lab": "Danwei Huangfu, MSKCC", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "Arima - A1, A2", "dataset": "in situ Hi-C on hESCs differentiated toward pancreatic cells", "condition": "definitive endoderm - HUES8", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "SOX17-eGFP idCAS9-KRAB HUES8 differentiated to definitive endoderm", "lab_name": "4DN DCIC, HMS"}}], "project_release": "2023-06-09", "digestion_enzyme": {"name": "Arima - A1, A2", "display_title": "Arima - A1, A2", "@type": ["Enzyme", "Item"], "status": "released", "@id": "/enzymes/Arima%20-%20A1,%20A2/", "uuid": "1b967af3-f275-4480-93d7-c6ce62a908c6", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "library_prep_kit": "KAPA HyperPrep kit", "contributing_labs": [{"@id": "/labs/christina-leslie-lab/", "@type": ["Lab", "Item"], "status": "current", "uuid": "b533abb2-66ea-4f89-b34f-22ba1954b38a", "display_title": "Christina Leslie, MSKCC", "correspondence": [{"contact_email": "Y2hyaXN0aW5hLmxlc2xpZUBnbWFpbC5jb20=", "@id": "/users/ddfc10d3-eea9-4183-9841-2c7e2e9f29bf/", "display_title": "Christina Leslie"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b533abb2-66ea-4f89-b34f-22ba1954b38a"]}}, {"@id": "/labs/effie-apostolou-lab/", "@type": ["Lab", "Item"], "status": "current", "uuid": "25604a5f-772b-43e2-a004-136ce41d0090", "display_title": "Effie Apostolou, CORNELL", "correspondence": [{"contact_email": "ZWZhMjAwMUBtZWQuY29ybmVsbC5lZHU=", "@id": "/users/9c7b948f-bc3e-40ee-8e23-c42b30268d03/", "display_title": "Effie Apostolou"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.25604a5f-772b-43e2-a004-136ce41d0090"]}}], "crosslinking_time": 10.0, "biosample_quantity": 2000000.0, "crosslinking_method": "1% Formaldehyde", "fragment_size_range": "200-600", "fragmentation_method": "sonication", "ligation_temperature": 23.0, "digestion_temperature": 37.0, "biosample_quantity_units": "cells", "crosslinking_temperature": 23.0, "fragment_size_selection_method": "SPRI beads", "@id": "/experiments-hi-c/4DNEX143ONJ6/", "@type": ["ExperimentHiC", "Experiment", "Item"], "uuid": "9310ff99-0d5b-43c2-89c3-a1b5960ff2ce", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "in situ Hi-C on SOX17-eGFP idCAS9-KRAB HUES8 differentiated to definitive endoderm with Arima - A1, A2 - 4DNEX143ONJ6", "external_references": [], "experiment_sets": [{"@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "display_title": "4DNESW8SIXN7", "accession": "4DNESW8SIXN7", "status": "released", "@id": "/experiment-set-replicates/4DNESW8SIXN7/", "uuid": "ef736e59-6e41-48d9-a307-0772e120a565", "experimentset_type": "replicate", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "produced_in_pub": {"status": "current", "display_title": "Luo R et al. (2023) PMID:37488417", "short_attribution": "Luo R et al. (2023)", "journal": "Nature genetics", "title": "Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear  enhancer gene regulatory activity during cell state transitions.", "@id": "/publications/9c7ecd32-9f21-45b7-b0d2-f2a2c1646ce9/", "date_published": "2023-08", "ID": "PMID:37488417", "abstract": "Comprehensive enhancer discovery is challenging because most enhancers,  especially those contributing to complex diseases, have weak effects on gene  expression. Our gene regulatory network modeling identified that nonlinear  enhancer gene regulation during cell state transitions can be leveraged to  improve the sensitivity of enhancer discovery. Using human embryonic stem cell  definitive endoderm differentiation as a dynamic transition system, we conducted  a mid-transition CRISPRi-based enhancer screen. We discovered a comprehensive set  of enhancers for each of the core endoderm-specifying transcription factors. Many  enhancers had strong effects mid-transition but weak effects post-transition,  consistent with the nonlinear temporal responses to enhancer perturbation  predicted by the modeling. Integrating three-dimensional genomic information, we  were able to develop a CTCF-loop-constrained Interaction Activity model that can  better predict functional enhancers compared to models that rely on Hi-C-based  enhancer-promoter contact frequency. Our study provides generalizable strategies  for sensitive and systematic enhancer discovery in both normal and pathological  cell state transitions.", "authors": ["Luo R", "Yan J", "Oh JW", "Xi W", "Shigaki D", "Wong W", "Cho HS", "Murphy D", "Cutler R", "Rosen BP", "Pulecio J", "Yang D", "Glenn RA", "Chen T", "Li QV", "Vierbuchen T", "Sidoli S", "Apostolou E", "Huangfu D", "Beer MA"], "uuid": "9c7ecd32-9f21-45b7-b0d2-f2a2c1646ce9", "@type": ["Publication", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"abstract": "Comprehensive enhancer discovery is challenging because most enhancers,  especially those contributing to complex diseases, have weak effects on gene  expression. Our gene regulatory network modeling identified that nonlinear  enhancer gene regulation during cell state transitions can be leveraged to  improve the sensitivity of enhancer discovery. Using human embryonic stem cell  definitive endoderm differentiation as a dynamic transition system, we conducted  a mid-transition CRISPRi-based enhancer screen. We discovered a comprehensive set  of enhancers for each of the core endoderm-specifying transcription factors. Many  enhancers had strong effects mid-transition but weak effects post-transition,  consistent with the nonlinear temporal responses to enhancer perturbation  predicted by the modeling. Integrating three-dimensional genomic information, we  were able to develop a CTCF-loop-constrained Interaction Activity model that can  better predict functional enhancers compared to models that rely on Hi-C-based  enhancer-promoter contact frequency. Our study provides generalizable strategies  for sensitive and systematic enhancer discovery in both normal and pathological  cell state transitions.", "date_published": "2023-08", "ID": "PMID:37488417", "uuid": "9c7ecd32-9f21-45b7-b0d2-f2a2c1646ce9", "journal": "Nature genetics", "title": "Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear  enhancer gene regulatory activity during cell state transitions.", "authors": ["Luo R", "Yan J", "Oh JW", "Xi W", "Shigaki D", "Wong W", "Cho HS", "Murphy D", "Cutler R", "Rosen BP", "Pulecio J", "Yang D", "Glenn RA", "Chen T", "Li QV", "Vierbuchen T", "Sidoli S", "Apostolou E", "Huangfu D", "Beer MA"], "@id": "/publications/9c7ecd32-9f21-45b7-b0d2-f2a2c1646ce9/", "display_title": "Luo R et al. (2023) PMID:37488417", "short_attribution": "Luo R et al. (2023)", "@type": ["Publication", "Item"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Enzyme", "value": "Arima - A1, A2", "combined": "Enzyme: Arima - A1, A2"}, "experiment_summary": "in situ Hi-C on SOX17-eGFP idCAS9-KRAB HUES8 differentiated to definitive endoderm with Arima - A1, A2", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSN9IPIX5/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing culture_duration", "Biosample missing morphology_image"], "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": []}