{"lab": {"@id": "/labs/benoit-bruneau-lab/", "@type": ["Lab", "Item"], "title": "Benoit Bruneau, UCSF", "uuid": "4dfac8f5-a868-4b29-9c11-a0932130e121", "correspondence": [{"contact_email": "YmVub2l0LmJydW5lYXVAZ2xhZHN0b25lLnVjc2YuZWR1", "@id": "/users/c015dffd-4ca1-4070-905f-8a04b3754b2b/", "display_title": "Benoit Bruneau"}], "status": "current", "display_title": "Benoit Bruneau, UCSF", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.4dfac8f5-a868-4b29-9c11-a0932130e121"]}}, "award": {"description": "RT-CDF: A major unanswered question is how chromatin topology coordinates human development and cellular differentiation, and how genome folding is differentially regulated in human disease. It is thought that three- dimensional (3D) chromatin organization is driven by transcriptional regulators, but fundamental mechanisms of this regulation as it relates to disease-relevant human cells have not been well explored. We propose to elucidate the temporally dynamic 3D nucleome (4DN) that underlies human cardiac differentiation, its molecular underpinnings, and the impact of mutations that underly defective 4DN organization in human congenital heart disease (CHD). CHDs are the most common birth defect and arise from abnormal heart development. The genetic basis of CHD is largely mutations in genes encoding chromatin modifiers (e.g. WDR5, KMT2D) and transcription factors (TFs, e.g. TBX5, GATA4), many of which also cause adult-onset arrhythmias. The impact of CHD mutations on the 4DN has not been explored. We hypothesize that 3D genome folding is highly regulated during cardiac differentiation and is impacted by disease-causing mutations in transcriptional regulators and non-coding elements. We will use iPS cell models and machine learning to elucidate dynamic 3D chromatin organization in human cardiomyocytes and endothelial cells during normal and diseased cardiac differentiation. We propose 3 specific aims: Aim 1: Establish a kilobase-scale 4D map of genome folding in human cardiomyocytes (CM) and endothelial cell (EC) differentiation. We will use directed differentiation of human iPS cells towards the two major cell types of the developing heart: CMs and ECs, and using microC across a fine time course of differentiation we will define at kilobase scale the 3D organization of the genome, capturing the states of developmental intermediates and the final differentiated cells. This aim will generate an essential integrated 4DN template for discovery in cardiac differentiation. In Aim 2: we will Determine the regulatory and disease-related basis for cardiac 3D chromatin organization. We will perform microC in iPS cell lines with CHD-associated mutations in transcriptional regulators, differentiated into CMs and ECs. These findings will establish the degree to which CHD is caused by abnormal genome folding and chromatin states, with important relevance to other human cardiovascular diseases. Finally, Aim 3 will address High-throughput screening of millions of CHD and synthetic non- coding mutations with a deep-learning model of dynamic genome folding. We will build a deep-learning model predicting 3D chromatin contact frequencies across cardiac differentiation at kilobase-resolution. By introducing thousands of CHD patient deletions and other non-coding mutations in silico, we will prioritize variants likely to interact with transcriptional regulators to cause disease through disrupted genome folding. Several candidates will be validated in engineered iPS cells differentiated into CMs and ECs. These results will provide a novel platform for computational discovery of disease variant impact across diverse human diseases", "center_title": "Bruneau", "@id": "/awards/1U01HL157989-01/", "project": "4DN", "uuid": "f910add4-950f-4e01-b9ea-6d88bfd3af99", "status": "current", "display_title": "GENETIC DETERMINANTS OF 4D GENOME FOLDING IN HUMAN CARDIAC DEVELOPMENT", "name": "1U01HL157989-01", "@type": ["Award", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "files": [{"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFIQEMXFCE/@@download/4DNFIQEMXFCE.fastq.gz", "uuid": "300125eb-c7ab-46dd-9bf1-a56663868f5e", "file_type_detailed": "reads (fastq)", "upload_key": "300125eb-c7ab-46dd-9bf1-a56663868f5e/4DNFIQEMXFCE.fastq.gz", "paired_end": "1", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFIQEMXFCE", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIQEMXFCE/", "file_size": 17904107025, "display_title": "4DNFIQEMXFCE.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 256366540, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIQEMXFCE/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/ad1ca7ed-1701-4412-a42e-7404ef7cee44/", "uuid": "ad1ca7ed-1701-4412-a42e-7404ef7cee44", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIRHQKS8A", "display_title": "4DNFIRHQKS8A.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "2", "@id": "/files-fastq/4DNFIRHQKS8A/", "uuid": "15447d33-76fd-4c43-8d84-99ecc5d3be7f", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}, {"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFIRHQKS8A/@@download/4DNFIRHQKS8A.fastq.gz", "uuid": "15447d33-76fd-4c43-8d84-99ecc5d3be7f", "file_type_detailed": "reads (fastq)", "upload_key": "15447d33-76fd-4c43-8d84-99ecc5d3be7f/4DNFIRHQKS8A.fastq.gz", "paired_end": "2", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFIRHQKS8A", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIRHQKS8A/", "file_size": 18174064590, "display_title": "4DNFIRHQKS8A.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 256366540, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIRHQKS8A/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/005ab60c-04d5-4bd4-8dfc-f24f70f36937/", "uuid": "005ab60c-04d5-4bd4-8dfc-f24f70f36937", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIQEMXFCE", "display_title": "4DNFIQEMXFCE.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "1", "@id": "/files-fastq/4DNFIQEMXFCE/", "uuid": "300125eb-c7ab-46dd-9bf1-a56663868f5e", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}, {"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFINSVSTD2/@@download/4DNFINSVSTD2.fastq.gz", "uuid": "60abdd00-038a-4047-83b4-6195b79632a4", "file_type_detailed": "reads (fastq)", "upload_key": "60abdd00-038a-4047-83b4-6195b79632a4/4DNFINSVSTD2.fastq.gz", "paired_end": "1", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFINSVSTD2", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFINSVSTD2/", "file_size": 10508291401, "display_title": "4DNFINSVSTD2.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 152116058, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFINSVSTD2/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/f2f5ab6f-89e8-43fa-8508-f647c7d2dad7/", "uuid": "f2f5ab6f-89e8-43fa-8508-f647c7d2dad7", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIO8JBQIM", "display_title": "4DNFIO8JBQIM.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "2", "@id": "/files-fastq/4DNFIO8JBQIM/", "uuid": "185c02eb-27e8-4f71-9f19-4bc76a454222", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}, {"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFIO8JBQIM/@@download/4DNFIO8JBQIM.fastq.gz", "uuid": "185c02eb-27e8-4f71-9f19-4bc76a454222", "file_type_detailed": "reads (fastq)", "upload_key": "185c02eb-27e8-4f71-9f19-4bc76a454222/4DNFIO8JBQIM.fastq.gz", "paired_end": "2", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFIO8JBQIM", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIO8JBQIM/", "file_size": 10626948874, "display_title": "4DNFIO8JBQIM.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 152116058, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIO8JBQIM/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/84457899-8cd1-4000-81cd-1a1240036146/", "uuid": "84457899-8cd1-4000-81cd-1a1240036146", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFINSVSTD2", "display_title": "4DNFINSVSTD2.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "1", "@id": "/files-fastq/4DNFINSVSTD2/", "uuid": "60abdd00-038a-4047-83b4-6195b79632a4", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}, {"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFIPWI8OC7/@@download/4DNFIPWI8OC7.fastq.gz", "uuid": "a434edfa-53b5-4662-8665-927e2b56c0f2", "file_type_detailed": "reads (fastq)", "upload_key": "a434edfa-53b5-4662-8665-927e2b56c0f2/4DNFIPWI8OC7.fastq.gz", "paired_end": "1", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFIPWI8OC7", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIPWI8OC7/", "file_size": 10576781431, "display_title": "4DNFIPWI8OC7.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 153657947, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIPWI8OC7/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/d5634dca-2681-4152-8e52-b757cfe68e3d/", "uuid": "d5634dca-2681-4152-8e52-b757cfe68e3d", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIXSX2DHD", "display_title": "4DNFIXSX2DHD.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "2", "@id": "/files-fastq/4DNFIXSX2DHD/", "uuid": "ad7f6a45-64c2-4132-9ec9-fad58646b319", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}, {"file_classification": "raw file", "status": "released", "href": "/files-fastq/4DNFIXSX2DHD/@@download/4DNFIXSX2DHD.fastq.gz", "uuid": "ad7f6a45-64c2-4132-9ec9-fad58646b319", "file_type_detailed": "reads (fastq)", "upload_key": "ad7f6a45-64c2-4132-9ec9-fad58646b319/4DNFIXSX2DHD.fastq.gz", "paired_end": "2", "dbxrefs": ["SRA:SRR31752331"], "file_type": "reads", "accession": "4DNFIXSX2DHD", "@type": ["FileFastq", "File", "Item"], "@id": "/files-fastq/4DNFIXSX2DHD/", "file_size": 10677988185, "display_title": "4DNFIXSX2DHD.fastq.gz", "quality_metric": {"display_title": "QualityMetricFastqc from 2024-12-19", "Total Sequences": 153657947, "overall_quality_status": "PASS", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIXSX2DHD/fastqc_report.html", "Sequence length": "151", "status": "released", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "@id": "/quality-metrics-fastqc/df57514e-ef01-496b-b459-9b448512bfe2/", "uuid": "df57514e-ef01-496b-b459-9b448512bfe2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"accession": "4DNFIPWI8OC7", "display_title": "4DNFIPWI8OC7.fastq.gz", "file_type_detailed": "reads (fastq)", "file_type": "reads", "paired_end": "1", "@id": "/files-fastq/4DNFIPWI8OC7/", "uuid": "a434edfa-53b5-4662-8665-927e2b56c0f2", "@type": ["FileFastq", "File", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"file_format": "fastq", "@type": ["FileFormat", "Item"], "status": "released", "@id": "/file-formats/fastq/", "uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "external_references": [{"ref": "SRA:SRR31752331", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR31752331"}]}], "status": "released", "aliases": ["bruneau-lab:experiment_hi-c-wtc11-TBX5het-atrial-diff-day20_B1_T1"], "dbxrefs": ["SRA:SRX27114209", "GEO:GSM8699827"], "protocol": {"status": "released", "uuid": "c27ea7a8-a56e-4538-b79a-f42b62d11214", "@id": "/protocols/c27ea7a8-a56e-4538-b79a-f42b62d11214/", "@type": ["Protocol", "Item"], "display_title": "Bruneau lab Hi-C 3.0 with Arima Kit", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNEXSRQ5AH2", "biosample": {"modifications_summary": "Crispr insertion for TBX5 gene", "@id": "/biosamples/4DNBSVQE38DT/", "accession": "4DNBSVQE38DT", "treatments_summary": "None", "biosource_summary": "WTC-11 differentiated to cardiac muscle cell", "display_title": "4DNBSVQE38DT", "uuid": "5f3dad74-4e3c-4472-b9aa-1ea449444ce1", "@type": ["Biosample", "Item"], "status": "released", "biosample_type": "in vitro differentiated cells", "biosource": [{"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "display_title": "4DN DCIC, HMS", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "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"]}}, "status": "released", "tissue": {"status": "released", "term_id": "CL:0000034", "uuid": "082f5be3-3617-4d3e-9ee9-78df53a71802", "display_title": "stem cell", "@id": "/ontology-terms/CL:0000034/", "@type": ["OntologyTerm", "Item"], "preferred_name": "stem cell", "slim_terms": [{"status": "current", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "@id": "/ontology-terms/GO:0005623/", "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "released", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "@id": "/ontology-terms/CL:0000000/", "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "synonyms": ["animal stem cell"], "term_name": "stem cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "aliases": ["4dn-dcic-lab:wtc-11-conklin-non-tier1"], "accession": "4DNSR19CALE3", "cell_line": {"@id": "/ontology-terms/EFO:0009747/", "status": "released", "uuid": "648cb723-fc6f-44b1-81a3-796c5d3e7868", "display_title": "WTC-11", "@type": ["OntologyTerm", "Item"], "slim_terms": [{"@id": "/ontology-terms/GO:0005623/", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@id": "/ontology-terms/CL:0000000/", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "synonyms": ["WTC-11", "WTC11"], "term_name": "GM25256", "term_id": "EFO:0009747", "preferred_name": "WTC-11", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "individual": {"@type": ["IndividualHuman", "Individual", "Item"], "@id": "/individuals-human/4DNINKRIXJE2/", "uuid": "c5a25acb-fad0-4f15-a909-677b1eed995d", "status": "released", "display_title": "4DNINKRIXJE2", "protected_data": false, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "description": "Induced pluripotent stem cells WTC-11 (GM25256)", "date_created": "2020-03-31T18:08:26.518658+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2020-03-31T18:08:26.578598+00:00"}, "biosource_type": "induced pluripotent stem cell", "cell_line_tier": "Unclassified", "public_release": "2020-03-31", "schema_version": "2", "project_release": "2020-03-31", "biosource_vendor": {"status": "released", "@id": "/vendors/bruce-conklin-gladstone/", "display_title": "Bruce Conklin, GLADSTONE", "@type": ["Vendor", "Item"], "uuid": "bcc25206-2f29-45dc-9a2e-c65d69fd00cb", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "@id": "/biosources/4DNSR19CALE3/", "@type": ["Biosource", "Item"], "uuid": "e1a1a9c3-c927-46f3-9975-12ad1671e04f", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "WTC-11 - 4DNSR19CALE3", "external_references": [], "biosource_name": "WTC-11", "biosource_category": ["WTC-11", "Human stem cell"], "organism": {"uuid": "7745b647-ff15-4ff3-9ced-b897d4e2983c", "@id": "/organisms/9606/", "status": "released", "@type": ["Organism", "Item"], "display_title": "H. sapiens", "name": "human", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "modifications": [{"modification_type": "Crispr", "@id": "/modifications/36146a01-2346-42b7-a8f2-5646833690dc/", "uuid": "36146a01-2346-42b7-a8f2-5646833690dc", "display_title": "Crispr insertion for TBX5 gene", "status": "released", "@type": ["Modification", "Item"], "genomic_change": "insertion", "description": "p.M51fs*16 - a 2 bp insertion in TBX5 that makes the ORF out of frame and causes a premature stop.", "target_of_mod": [{"organism_name": "human", "status": "released", "@id": "/bio-features/ac958a19-6717-46e3-9409-27cd361fbb94/", "feature_type": {"@id": "/ontology-terms/SO:0000704/", "@type": ["OntologyTerm", "Item"], "display_title": "gene", "status": "released", "uuid": "0231da78-1adc-4b8a-89b9-4f91908412a3", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "ac958a19-6717-46e3-9409-27cd361fbb94", "relevant_genes": [{"@type": ["Gene", "Item"], "uuid": "c684ac98-144f-4c3f-b928-b2beef8a2595", "@id": "/genes/6910/", "status": "released", "display_title": "TBX5", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@type": ["BioFeature", "Item"], "display_title": "TBX5 gene", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "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", "Biosample is a stem cell line with unknown passage number missing karyotype"], "badge": {"warning": "Biosample Metadata Incomplete", "badge_classification": "Warning", "title": "Biosample Metadata Incomplete", "display_title": "Biosample Metadata Incomplete", "badge_icon": "/static/img/badges/biosample-icon.svg", "@id": "/badges/biosample-metadata-incomplete/", "@type": ["Badge", "Item"], "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", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pcr_cycles": 9, "sop_mapping": {"has_sop": "No"}, "date_created": "2024-12-18T17:03:51.811496+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-01-23T19:59:50.186430+00:00"}, "ligation_time": 15, "digestion_time": 60, "public_release": "2025-01-16", "schema_version": "2", "experiment_type": {"display_title": "in situ Hi-C", "experiment_category": "Sequencing", "uuid": "a2920a38-cdba-4ff0-b4f0-c6bb53257747", "status": "released", "title": "in situ Hi-C", "@id": "/experiment-types/in-situ-hi-c/", "@type": ["ExperimentType", "Item"], "assay_subclass_short": "Hi-C", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "ligation_volume": 0.2, "processed_files": [{"accession": "4DNFIOPN7AWK", "file_size": 113415793866, "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/0cce0b9a-b99f-4c9c-b01d-11fa03af7943/4DNFIOPN7AWK.bam", "display_title": "4DNFIOPN7AWK.bam", "file_format": {"uuid": "d13d06cf-218e-4f61-aaf0-91f226248b3c", "file_format": "bam", "status": "released", "@id": "/file-formats/bam/", "@type": ["FileFormat", "Item"], "display_title": "bam", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "href": "/files-processed/4DNFIOPN7AWK/@@download/4DNFIOPN7AWK.bam", "status": "released", "@id": "/files-processed/4DNFIOPN7AWK/", "@type": ["FileProcessed", "File", "Item"], "file_type": "alignments", "file_type_detailed": "alignments (bam)", "uuid": "0cce0b9a-b99f-4c9c-b01d-11fa03af7943", "file_classification": "processed file", "upload_key": "0cce0b9a-b99f-4c9c-b01d-11fa03af7943/4DNFIOPN7AWK.bam", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "external_references": [], "track_and_facet_info": {"experimental_lab": "Benoit Bruneau, UCSF", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "DdeI and DpnII", "dataset": "Hi-C on WTC-11 differentiated to cardiac muscle cell", "condition": "20 day differentiatiation to cardiac cells - TBX5 heterozygous", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "WTC-11 differentiated to cardiac muscle cell", "lab_name": "4DN DCIC, HMS"}}, {"accession": "4DNFIAVDPHUH", "file_size": 7722199961, "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/900e64b0-538b-499c-9401-fa9000f4a907/4DNFIAVDPHUH.pairs.gz", "display_title": "4DNFIAVDPHUH.pairs.gz", "file_format": {"uuid": "d13d06cf-218e-4f61-aaf0-91f226248b2c", "file_format": "pairs", "status": "released", "@id": "/file-formats/pairs/", "@type": ["FileFormat", "Item"], "display_title": "pairs", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "href": "/files-processed/4DNFIAVDPHUH/@@download/4DNFIAVDPHUH.pairs.gz", "status": "released", "@id": "/files-processed/4DNFIAVDPHUH/", "@type": ["FileProcessed", "File", "Item"], "file_type": "contact list-replicate", "file_type_detailed": "contact list-replicate (pairs)", "uuid": "900e64b0-538b-499c-9401-fa9000f4a907", "file_classification": "processed file", "upload_key": "900e64b0-538b-499c-9401-fa9000f4a907/4DNFIAVDPHUH.pairs.gz", "quality_metric": {"url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIAVDPHUH/pairsqc_report.html", "uuid": "37f9b0e0-208a-4dce-b0e1-6fa560b5f1e5", "overall_quality_status": "PASS", "@type": ["QualityMetricPairsqc", "QualityMetric", "Item"], "@id": "/quality-metrics-pairsqc/37f9b0e0-208a-4dce-b0e1-6fa560b5f1e5/", "Total reads": 416369993, "display_title": "QualityMetricPairsqc from 2025-01-05", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "quality_metric_summary": [{"title": "Filtered Reads", "value": "416369993", "numberType": "integer"}, {"title": "Cis reads (>20kb)", "value": "43.177", "tooltip": "Percent of filtered reads (=179.78m)", "numberType": "percent"}, {"title": "Short cis reads", "value": "41.18", "tooltip": "Percent of filtered reads (=171.46m)", "numberType": "percent"}, {"title": "Trans Reads", "value": "15.643", "tooltip": "Percent of filtered reads (=65.13m)", "numberType": "percent"}]}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "external_references": [], "track_and_facet_info": {"experimental_lab": "Benoit Bruneau, UCSF", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "DdeI and DpnII", "dataset": "Hi-C on WTC-11 differentiated to cardiac muscle cell", "condition": "20 day differentiatiation to cardiac cells - TBX5 heterozygous", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "WTC-11 differentiated to cardiac muscle cell", "lab_name": "4DN DCIC, HMS"}}], "project_release": "2025-01-16", "digestion_enzyme": {"name": "DdeI and DpnII", "uuid": "d2c07cb7-930d-4eed-a1c0-6ba2767ec9ea", "display_title": "DdeI and DpnII", "status": "released", "@id": "/enzymes/DdeI%20and%20DpnII/", "@type": ["Enzyme", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "library_prep_kit": "KAPA Hyper Prep Kit (Roche #7962347001)", "contributing_labs": [{"@type": ["Lab", "Item"], "uuid": "bae16ec7-6e90-48ec-ba27-fa4f6510489c", "@id": "/labs/katherine-pollard-lab/", "correspondence": [{"contact_email": "a2F0aGVyaW5lLnBvbGxhcmRAZ2xhZHN0b25lLnVjc2YuZWR1", "@id": "/users/9b476d96-70d4-4eae-b12f-c0f55d849831/", "display_title": "Katherine Pollard"}], "display_title": "Katherine Pollard, UCSF", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.bae16ec7-6e90-48ec-ba27-fa4f6510489c"]}}], "crosslinking_time": 50, "enzyme_lot_number": "DdeI = NEB #R0175L (lot #10095805), DpnII = NEB #R0543M (lot #10104549)", "biosample_quantity": 5000000, "crosslinking_method": "1% Formaldehyde and 3mM DSG", "fragment_size_range": "200-600", "fragmentation_method": "sonication", "ligation_temperature": 25, "average_fragment_size": 400, "digestion_temperature": 37, "biosample_quantity_units": "cells", "crosslinking_temperature": 23, "library_preparation_date": "2023-05-25", "fragment_size_selection_method": "SPRI beads", "@id": "/experiments-hi-c/4DNEXSRQ5AH2/", "@type": ["ExperimentHiC", "Experiment", "Item"], "uuid": "feeda2de-6d16-44d6-8985-f57a8d8538e1", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "in situ Hi-C on WTC-11 differentiated to cardiac muscle cell with DdeI and DpnII - 4DNEXSRQ5AH2", "external_references": [{"ref": "SRA:SRX27114209", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRX27114209"}, {"ref": "GEO:GSM8699827", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM8699827"}], "experiment_sets": [{"experimentset_type": "replicate", "uuid": "51a3cac2-7b6f-4f5a-b107-a201b61d8e0e", "accession": "4DNES4NO6DRP", "display_title": "4DNES4NO6DRP", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNES4NO6DRP/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "produced_in_pub": {"display_title": "Grant ZL et al. (2025) PMID:39829922", "uuid": "94bcbb78-451f-4ed7-8950-797163402ccd", "status": "current", "authors": ["Grant ZL", "Kuang S", "Zhang S", "Horrillo AJ", "Rao KS", "Kameswaran V", "Joubran C", "Lau PK", "Dong K", "Yang B", "Bartosik WM", "Zemke NR", "Ren B", "Kathiriya IS", "Pollard KS", "Bruneau BG"], "@type": ["Publication", "Item"], "abstract": "Dosage-sensitive transcription factors (TFs) underlie altered gene regulation in  human developmental disorders, and cell-type specific gene regulation is linked  to the reorganization of 3D chromatin during cellular differentiation. Here, we  show dose-dependent regulation of chromatin organization by the congenital heart  disease (CHD)-linked, lineage-restricted TF TBX5 in human cardiomyocyte  differentiation. Genome organization, including compartments, topologically  associated domains, and chromatin loops, are sensitive to reduced TBX5 dosage in  a human model of CHD, with variations in response across individual cells.  Regions normally bound by TBX5 are especially sensitive, while co-occupancy with  CTCF partially protects TBX5-bound TAD boundaries and loop anchors. These results  highlight the importance of lineage-restricted TF dosage in cell-type specific 3D  chromatin dynamics, suggesting a new mechanism for TF-dependent disease.", "@id": "/publications/94bcbb78-451f-4ed7-8950-797163402ccd/", "title": "Dose-dependent sensitivity of human 3D chromatin to a heart disease-linked  transcription factor.", "short_attribution": "Grant ZL et al. (2025)", "ID": "PMID:39829922", "date_published": "2025-01-12", "journal": "bioRxiv : the preprint server for biology", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"status": "current", "@id": "/publications/94bcbb78-451f-4ed7-8950-797163402ccd/", "journal": "bioRxiv : the preprint server for biology", "title": "Dose-dependent sensitivity of human 3D chromatin to a heart disease-linked  transcription factor.", "date_published": "2025-01-12", "abstract": "Dosage-sensitive transcription factors (TFs) underlie altered gene regulation in  human developmental disorders, and cell-type specific gene regulation is linked  to the reorganization of 3D chromatin during cellular differentiation. Here, we  show dose-dependent regulation of chromatin organization by the congenital heart  disease (CHD)-linked, lineage-restricted TF TBX5 in human cardiomyocyte  differentiation. Genome organization, including compartments, topologically  associated domains, and chromatin loops, are sensitive to reduced TBX5 dosage in  a human model of CHD, with variations in response across individual cells.  Regions normally bound by TBX5 are especially sensitive, while co-occupancy with  CTCF partially protects TBX5-bound TAD boundaries and loop anchors. These results  highlight the importance of lineage-restricted TF dosage in cell-type specific 3D  chromatin dynamics, suggesting a new mechanism for TF-dependent disease.", "authors": ["Grant ZL", "Kuang S", "Zhang S", "Horrillo AJ", "Rao KS", "Kameswaran V", "Joubran C", "Lau PK", "Dong K", "Yang B", "Bartosik WM", "Zemke NR", "Ren B", "Kathiriya IS", "Pollard KS", "Bruneau BG"], "short_attribution": "Grant ZL et al. (2025)", "uuid": "94bcbb78-451f-4ed7-8950-797163402ccd", "ID": "PMID:39829922", "@type": ["Publication", "Item"], "display_title": "Grant ZL et al. (2025) PMID:39829922", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Enzyme", "value": "DdeI and DpnII", "combined": "Enzyme: DdeI and DpnII"}, "experiment_summary": "in situ Hi-C on WTC-11 differentiated to cardiac muscle cell with DdeI and DpnII", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSVQE38DT/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing culture_duration", "Biosample missing morphology_image", "Biosample is a stem cell line with unknown passage number missing karyotype"], "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": []}