{"lab": {"status": "current", "display_title": "Danwei Huangfu, MSKCC", "correspondence": [{"contact_email": "aHVhbmdmdWRAbXNrY2Mub3Jn", "@id": "/users/b9ddcafc-fc2d-401d-98a6-dd1cb39b2982/", "display_title": "Danwei Huangfu"}], "uuid": "bd4a15cf-e3f4-4938-933e-787883a48d7c", "title": "Danwei Huangfu, MSKCC", "@id": "/labs/danwei-huangfu-lab/", "@type": ["Lab", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.bd4a15cf-e3f4-4938-933e-787883a48d7c"]}}, "award": {"status": "current", "name": "1U01DK128852-01", "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.", "@id": "/awards/1U01DK128852-01/", "center_title": "OFHHD - Huangfu", "uuid": "8432a44c-4da7-446b-9080-f4fae299ebd6", "@type": ["Award", "Item"], "project": "4DN", "display_title": "DISCOVERY OF DIABETES-RELEVANT BETA CELL ENHANCERS THROUGH 4D ENHANCER MAPPING, INTEGRATIVE ANALYSIS, AND LARGE-SCALE CRISPRI PERTURBATION SCREENS", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "md5sum": "fb585b93070eadc28ffababce6d689c6", "status": "released", "aliases": ["danwei-huang-lab:filefastq_hi-c_pdx1-GFP_idCAS9-KRAB_H1_DE_B1_T1_f1_r1"], "filename": "PDX1GFP_IGO_11002_5_S5_R1_001.fastq.gz", "accession": "4DNFIVXGC95R", "file_size": 6621259248, "file_type": "reads", "paired_end": "1", "file_format": {"uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "@type": ["FileFormat", "Item"], "display_title": "fastq", "file_format": "fastq", "status": "released", "@id": "/file-formats/fastq/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "read_length": 100, "date_created": "2023-05-31T15:10:41.642553+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-08-07T21:25:04.893380+00:00"}, "related_files": [{"file": {"@type": ["FileFastq", "File", "Item"], "status": "released", "uuid": "383fe654-ca5d-406f-96c9-f144147251ed", "display_title": "4DNFIF9I4KUA.fastq.gz", "accession": "4DNFIF9I4KUA", "@id": "/files-fastq/4DNFIF9I4KUA/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "relationship_type": "paired with"}], "content_md5sum": "f64bc045a7c3626712c146bb9c1a1628", "public_release": "2023-06-09", "quality_metric": {"@id": "/quality-metrics-fastqc/2900f7a4-d5c7-41bf-8f2f-83b4cf7fc48b/", "uuid": "2900f7a4-d5c7-41bf-8f2f-83b4cf7fc48b", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "overall_quality_status": "PASS", "status": "released", "Sequence length": "100", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIVXGC95R/fastqc_report.html", "display_title": "QualityMetricFastqc from 2023-06-01", "Total Sequences": 115366414, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "schema_version": "2", "file_first_line": "@K00217:451:HHWNLBBXY:7:1101:2118:1226 1:N:0:NTGTCAGA", "project_release": "2023-06-09", "contributing_labs": [{"correspondence": [{"contact_email": "Y2hyaXN0aW5hLmxlc2xpZUBnbWFpbC5jb20=", "@id": "/users/ddfc10d3-eea9-4183-9841-2c7e2e9f29bf/", "display_title": "Christina Leslie"}], "display_title": "Christina Leslie, MSKCC", "uuid": "b533abb2-66ea-4f89-b34f-22ba1954b38a", "@type": ["Lab", "Item"], "@id": "/labs/christina-leslie-lab/", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b533abb2-66ea-4f89-b34f-22ba1954b38a"]}}, {"correspondence": [{"contact_email": "ZWZhcG9zdG9sb3VAZ21haWwuY29t", "@id": "/users/9c7b948f-bc3e-40ee-8e23-c42b30268d03/", "display_title": "Effie Apostolou"}], "display_title": "Effie Apostolou, CORNELL", "uuid": "25604a5f-772b-43e2-a004-136ce41d0090", "@type": ["Lab", "Item"], "@id": "/labs/effie-apostolou-lab/", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.25604a5f-772b-43e2-a004-136ce41d0090"]}}], "file_classification": "raw file", "@id": "/files-fastq/4DNFIVXGC95R/", "@type": ["FileFastq", "File", "Item"], "uuid": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "4DNFIVXGC95R.fastq.gz", "external_references": [], "experiments": [{"display_title": "in situ Hi-C on PDX1-eGFP dCAS9-KRAB H1 differentiated to definitive endoderm with Arima - A1, A2 - 4DNEXNDOLHY1", "status": "released", "@id": "/experiments-hi-c/4DNEXNDOLHY1/", "@type": ["ExperimentHiC", "Experiment", "Item"], "accession": "4DNEXNDOLHY1", "uuid": "3aa126e6-dad3-47c7-92f2-69a2808be7c9", "biosample": {"biosource_summary": "PDX1-eGFP dCAS9-KRAB H1 differentiated to definitive endoderm", "@type": ["Biosample", "Item"], "uuid": "2dd821b9-b8b0-4621-a8f8-8d6b2128d2bd", "@id": "/biosamples/4DNBSE3F5ADT/", "status": "released", "modifications_summary": "None", "display_title": "4DNBSE3F5ADT", "accession": "4DNBSE3F5ADT", "treatments_summary": "None", "biosource": [{"biosource_type": "stem cell derived cell line", "cell_line_tier": "Unclassified", "status": "released", "@id": "/biosources/4DNSRFCDHG7X/", "@type": ["Biosource", "Item"], "uuid": "760c778e-cd2b-4cd9-9eac-b1dd8e3024de", "display_title": "PDX1-eGFP dCAS9-KRAB H1 - 4DNSRFCDHG7X", "override_biosource_name": "PDX1-eGFP dCAS9-KRAB H1", "tissue": {"term_name": "stem cell", "preferred_name": "stem cell", "@type": ["OntologyTerm", "Item"], "term_id": "CL:0000034", "display_title": "stem cell", "status": "released", "uuid": "082f5be3-3617-4d3e-9ee9-78df53a71802", "@id": "/ontology-terms/CL:0000034/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "cell_line": {"display_title": "H1-hESC", "preferred_name": "H1-hESC", "@id": "/ontology-terms/EFO:0003042/", "status": "released", "term_name": "H1-hESC", "uuid": "c3f6e06f-900e-45f9-9c23-983c5673f58d", "@type": ["OntologyTerm", "Item"], "term_id": "EFO:0003042", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "organism": {"status": "released", "scientific_name": "Homo sapiens", "name": "human", "display_title": "H. sapiens", "uuid": "7745b647-ff15-4ff3-9ced-b897d4e2983c", "@type": ["Organism", "Item"], "@id": "/organisms/9606/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "individual": {"@type": ["IndividualHuman", "Individual", "Item"], "display_title": "4DNIN3RG3ZKE", "status": "released", "uuid": "c97775b7-3d00-4132-9598-863797b8ef14", "protected_data": false, "@id": "/individuals-human/4DNIN3RG3ZKE/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "cell_culture_details": [{"in_vitro_differentiated": "Yes", "@type": ["BiosampleCellCulture", "Item"], "display_title": "BiosampleCellCulture from 2023-05-31", "@id": "/biosample-cell-cultures/094dee69-8d49-4336-b665-8db21358a128/", "uuid": "094dee69-8d49-4336-b665-8db21358a128", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "digestion_enzyme": {"display_title": "Arima - A1, A2", "@type": ["Enzyme", "Item"], "status": "released", "@id": "/enzymes/Arima%20-%20A1,%20A2/", "uuid": "1b967af3-f275-4480-93d7-c6ce62a908c6", "name": "Arima - A1, A2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "last_modified": {"date_modified": "2024-07-19T13:21:44.793534+00:00"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "experiment_type": {"title": "in situ Hi-C", "@type": ["ExperimentType", "Item"], "display_title": "in situ Hi-C", "uuid": "a2920a38-cdba-4ff0-b4f0-c6bb53257747", "status": "released", "@id": "/experiment-types/in-situ-hi-c/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "experiment_sets": [{"status": "released", "uuid": "cd7fb574-df77-4e2b-b923-f1805fa7f683", "display_title": "4DNESI1DNSGF", "experimentset_type": "replicate", "accession": "4DNESI1DNSGF", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESI1DNSGF/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}]}], "file_type_detailed": "reads (fastq)", "track_and_facet_info": {"experimental_lab": "Danwei Huangfu, MSKCC", "experiment_type": "in situ Hi-C", "experiment_bucket": "raw file", "assay_info": "Arima - A1, A2", "dataset": "in situ Hi-C on hESCs differentiated toward pancreatic cells", "condition": "definitive endoderm - H1", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "PDX1-eGFP dCAS9-KRAB H1 differentiated to definitive endoderm", "lab_name": "Danwei Huangfu, MSKCC"}, "title": "4DNFIVXGC95R", "href": "/files-fastq/4DNFIVXGC95R/@@download/4DNFIVXGC95R.fastq.gz", "upload_key": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b/4DNFIVXGC95R.fastq.gz", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/files/b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b/4DNFIVXGC95R.fastq.gz", "tsv_notes": "", "workflow_run_inputs": [{"@type": ["WorkflowRunAwsem", "WorkflowRun", "Item"], "uuid": "846fb33e-6e85-4f6e-8c1e-f53539991962", "status": "released", "@id": "/workflow-runs-awsem/846fb33e-6e85-4f6e-8c1e-f53539991962/", "display_title": "md5 0.2.6 run 2023-06-01 14:27:33.485895", "input_files": [{"workflow_argument_name": "input_file", "value": {"status": "released", "uuid": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b", "accession": "4DNFIVXGC95R", "@type": ["FileFastq", "File", "Item"], "display_title": "4DNFIVXGC95R.fastq.gz", "filename": "PDX1GFP_IGO_11002_5_S5_R1_001.fastq.gz", "@id": "/files-fastq/4DNFIVXGC95R/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "file_format": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "workflow": {"display_title": "md5 0.2.6 - 4DNWF2HFF82B", "uuid": "c77a117b-9a58-477e-aaa5-291a109a99f6", "status": "released", "title": "md5 0.2.6", "@id": "/workflows/4DNWF2HFF82B/", "@type": ["Workflow", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "output_files": [{"workflow_argument_name": "report"}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["WorkflowRunAwsem", "WorkflowRun", "Item"], "uuid": "234204ef-f964-4987-a029-bd93caa56b3d", "status": "released", "@id": "/workflow-runs-awsem/234204ef-f964-4987-a029-bd93caa56b3d/", "display_title": "fastqc v2 run 2023-06-01 15:06:51.972809", "input_files": [{"workflow_argument_name": "input_fastq", "value": {"status": "released", "uuid": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b", "accession": "4DNFIVXGC95R", "@type": ["FileFastq", "File", "Item"], "display_title": "4DNFIVXGC95R.fastq.gz", "filename": "PDX1GFP_IGO_11002_5_S5_R1_001.fastq.gz", "@id": "/files-fastq/4DNFIVXGC95R/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "file_format": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "workflow": {"display_title": "FastQC v2 - 4DNWFAEU2GB7", "uuid": "49e96b51-ed6c-4418-a693-d0e9f79adfa5", "status": "released", "title": "FastQC v2", "@id": "/workflows/4DNWFAEU2GB7/", "@type": ["Workflow", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "output_files": [{"workflow_argument_name": "report_zip", "value_qc": {"uuid": "2900f7a4-d5c7-41bf-8f2f-83b4cf7fc48b", "status": "released", "@id": "/quality-metrics-fastqc/2900f7a4-d5c7-41bf-8f2f-83b4cf7fc48b/", "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIVXGC95R/fastqc_report.html", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "display_title": "QualityMetricFastqc from 2023-06-01", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["WorkflowRunAwsem", "WorkflowRun", "Item"], "uuid": "f4c8d6d4-0cfa-410a-a05b-78307e7cff5d", "status": "released", "@id": "/workflow-runs-awsem/f4c8d6d4-0cfa-410a-a05b-78307e7cff5d/", "display_title": "fastq-first-line v2 run 2023-06-01 14:46:58.916767", "input_files": [{"workflow_argument_name": "fastq", "value": {"status": "released", "uuid": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b", "accession": "4DNFIVXGC95R", "@type": ["FileFastq", "File", "Item"], "display_title": "4DNFIVXGC95R.fastq.gz", "filename": "PDX1GFP_IGO_11002_5_S5_R1_001.fastq.gz", "@id": "/files-fastq/4DNFIVXGC95R/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "file_format": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "workflow": {"display_title": "Getting first line of fastq file - 4DNWFASTQFO1", "uuid": "93a1a931-d55d-4623-adfb-0fa735daf6ae", "status": "released", "title": "Getting first line of fastq file", "@id": "/workflows/4DNWFASTQFO1/", "@type": ["Workflow", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "output_files": [{"workflow_argument_name": "first_line"}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["WorkflowRunAwsem", "WorkflowRun", "Item"], "uuid": "300c8040-46ec-40c7-9a07-288f71957149", "status": "released", "@id": "/workflow-runs-awsem/300c8040-46ec-40c7-9a07-288f71957149/", "display_title": "bwa-mem 0.2.6 run 2023-06-01 20:07:16.849729", "input_files": [{"workflow_argument_name": "bwa_index", "value": {"status": "released", "uuid": "1f53df95-4cf3-41cc-971d-81bb16c486dd", "accession": "4DNFIZQZ39L9", "@type": ["FileReference", "File", "Item"], "display_title": "4DNFIZQZ39L9.bwaIndex.tgz", "filename": "hg38.bwaIndex.tgz", "@id": "/files-reference/4DNFIZQZ39L9/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "bwaIndex", "@id": "/file-formats/bwaIndex/", "uuid": "d13d06cf-218e-4f61-55f0-91f226248b2c", "status": "released", "file_format": "bwaIndex", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"workflow_argument_name": "fastq1", "value": {"status": "released", "uuid": "b3a32ca3-e0a1-4c94-9b00-b9c4134c6e3b", "accession": "4DNFIVXGC95R", "@type": ["FileFastq", "File", "Item"], "display_title": "4DNFIVXGC95R.fastq.gz", "filename": "PDX1GFP_IGO_11002_5_S5_R1_001.fastq.gz", "@id": "/files-fastq/4DNFIVXGC95R/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "file_format": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"workflow_argument_name": "fastq2", "value": {"status": "released", "uuid": "383fe654-ca5d-406f-96c9-f144147251ed", "accession": "4DNFIF9I4KUA", "@type": ["FileFastq", "File", "Item"], "display_title": "4DNFIF9I4KUA.fastq.gz", "filename": "PDX1GFP_IGO_11002_5_S5_R2_001.fastq.gz", "@id": "/files-fastq/4DNFIF9I4KUA/", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "fastq", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "status": "released", "file_format": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "workflow": {"display_title": "Alignment for Hi-C using bwa-mem 0.2.6 - 4DNWF84NFOQP", "uuid": "3feedadc-50f9-4bb4-919b-09a8b731d0cc", "status": "released", "title": "Alignment for Hi-C using bwa-mem 0.2.6", "@id": "/workflows/4DNWF84NFOQP/", "@type": ["Workflow", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "output_files": [{"workflow_argument_name": "out_bam", "value": {"status": "released", "accession": "4DNFI2CG8IGH", "@id": "/files-processed/4DNFI2CG8IGH/", "uuid": "6cf2943f-296f-4dd1-a229-7949d5807159", "@type": ["FileProcessed", "File", "Item"], "display_title": "4DNFI2CG8IGH.bam", "file_format": {"uuid": "d13d06cf-218e-4f61-aaf0-91f226248b3c", "status": "released", "file_format": "bam", "@id": "/file-formats/bam/", "@type": ["FileFormat", "Item"], "display_title": "bam", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "workflow_run_outputs": [], "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}