{"lab": {"@id": "/labs/erez-liebermanaiden-lab/", "title": "Erez Lieberman Aiden, BCM", "display_title": "Erez Lieberman Aiden, BCM", "uuid": "5771d772-1d10-43ea-bec1-0ea8c5a58503", "correspondence": [{"contact_email": "ZXJlekBlcmV6LmNvbQ==", "@id": "/users/60938b2e-e120-4c4f-9ddb-001296021df7/", "display_title": "Erez Lieberman Aiden"}], "status": "current", "@type": ["Lab", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.5771d772-1d10-43ea-bec1-0ea8c5a58503"]}}, "award": {"description": "Biological systems contain a large number of components whose physical interactions bring about cellular processes. A fundamental problem in molecular biology is to catalog these interactions and to decipher their functional consequences. High throughput sequencing has made it possible to characterize some of these interactions rapidly, at high-resolution, and in vivo (e.g., protein-DNA binding via ChIP-Seq and protein-RNA binding via RIP-Seq). But many interactions are not susceptible to these methods (e.g., RNA- RNA complexes, ncRNA-DNA binding, and - aside from recent work described below - DNA-DNA contacts and genome folding.) This gap may be bridged by coupling high-throughput sequencing with proximity-ligation-based methods. In proximity ligation, spatially proximate nucleic acids ligate to one another, forming a chimeric oligo. Observation of a chimera composed of X and Y suggests that X and Y must have been near one another in the original sample. As a result, questions about spatial arrangement become questions about sequence composition, making it possible to take advantage of high-throughput sequencing. Nevertheless, the development of these approaches is challenging: they involve subtle molecular biology and produce massive high-dimensional datasets requiring wholly new analytical paradigms including extensive physical modeling. We recently developed Hi-C, the first technology that couples proximity ligation and high-throughput sequencing in an unbiased, genome-wide fashion (Lieberman-Aiden et al., Science, 2009). Hi-C uses a DNA-DNA proximity ligation step to identify long-range physical contacts between genomic DNA loci in vivo. We used Hi-C to create a low-resolution three-dimensional map of the human genome, and made two significant discoveries: (1) genetic regulation is accompanied by the three-dimensional movement of genes from an 'on' compartment to an 'off' compartment, and vice-versa; (2) a never-before-seen macromolecular state, the fractal globule, which couples extraordinary spatial density and a total absence of knots. Here, we propose to dramatically extend the above work, by building a new generation of tools for systematically exploring the spatial organization of genomes, RNAs, and proteins, and by applying these tools to explore how RNAs and proteins establish and regulate the three-dimensional architecture of the genome. We will accomplish this through three specific research aims: (1) We will create an ensemble of new technologies combining proximity ligation and sequencing to enable comprehensive mapping of (a) DNA-RNA contacts [via DNA-RNA proximity ligation]; (b) RNA-RNA complexes [via RNA-RNA proximity ligation]; (c) selected protein-protein complexes [via probe-coupled proximity ligation]. We will use these methods to generate maps of biomolecular contacts in vivo. (2) We will create high-resolution Hi-C maps of mammalian genomes, comprehensively mapping promoter-enhancer contacts and exploring large-scale organizational features such as transcription factories. (3) We will develop new analytical approaches that combine the data produced by (1) and (2) with new (a) informatic tools, (b) computational analyses, (c) physical simulations, and (d) rigorous theoretical methods. We will characterize how physical interactions change during differentiation and tumorigenesis; identify the RNAs, proteins and pathways that that are most crucial in regulating genome folding, and produce detailed physical models of these pathways and how they modulate the physical structure of the genome. We plan to initially apply these techniques to characterize murine ES cells differentiating down a neural lineage, and later to differentiating human ES cells and to primary tumors. This effort will produce powerful new molecular methods which will dramatically improve our ability to assess the spatial arrangement of cellular components. It will transform our understanding of how mammalian genomes fold inside the nucleus. It will reveal how specific physical interactions between DNA, RNA, and protein play a role in differentiation, tumorigenesis, and genome folding, and suggest new drug targets in the process. Finally, this work will generate a series of datasets that will serve as valuable resources for the scientific community as a whole. Public Health Relevance: Biological systems contain a large number of components whose physical interactions bring about cellular processes, but our tools for identifying many of these biomolecular interactions are laborious and slow. We recently developed the Hi-C method for reconstructing the architecture of the human genome, and will extend this technological approach to map interactions between DNA, RNA, and protein in vivo and at high-throughput. We will use these maps to study how genome folding regulates cell function, and to characterize the process of cellular differentiation and tumorigenesis, identifying crucial biomolecular pathways and potential drug targets.", "name": "OD008540-01", "@id": "/awards/OD008540-01/", "project": "External", "status": "current", "uuid": "36a06537-7831-494d-b10d-3e9fea931021", "center_title": "Lieberman Aiden", "@type": ["Award", "Item"], "display_title": "EXPLORING HOW THE GENOME FOLDS THROUGH PROXIMITY LIGATION AND SEQUENCING", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "files": [{"display_title": "4DNFIKVOAG6P.fastq.gz", "href": "/files-fastq/4DNFIKVOAG6P/@@download/4DNFIKVOAG6P.fastq.gz", "@type": ["FileFastq", "File", "Item"], "upload_key": "f7ede7ed-a440-47ec-b681-b742bb635f48/4DNFIKVOAG6P.fastq.gz", "status": "released", "file_type_detailed": "reads (fastq)", "dbxrefs": ["SRA:SRR1658814"], "@id": "/files-fastq/4DNFIKVOAG6P/", "accession": "4DNFIKVOAG6P", "file_classification": "raw file", "uuid": "f7ede7ed-a440-47ec-b681-b742bb635f48", "paired_end": "1", "file_size": 39283971, "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "status": "released", "file_format": "fastq", "@id": "/file-formats/fastq/", "@type": ["FileFormat", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIKVOAG6P/fastqc_report.html", "display_title": "QualityMetricFastqc from 2017-08-11", "uuid": "4c4ca141-c7e4-4eee-a01c-48f0805df5d4", "overall_quality_status": "PASS", "@id": "/quality-metrics-fastqc/4c4ca141-c7e4-4eee-a01c-48f0805df5d4/", "status": "released", "Total Sequences": 617683, "Sequence length": "95", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"file_type_detailed": "reads (fastq)", "@type": ["FileFastq", "File", "Item"], "file_type": "reads", "paired_end": "2", "accession": "4DNFI9TW5LR8", "uuid": "58c8e297-2396-404d-973f-3cfa7c7bcb18", "@id": "/files-fastq/4DNFI9TW5LR8/", "status": "released", "display_title": "4DNFI9TW5LR8.fastq.gz", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": [{"ref": "SRA:SRR1658814", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR1658814"}]}, {"display_title": "4DNFI9TW5LR8.fastq.gz", "href": "/files-fastq/4DNFI9TW5LR8/@@download/4DNFI9TW5LR8.fastq.gz", "@type": ["FileFastq", "File", "Item"], "upload_key": "58c8e297-2396-404d-973f-3cfa7c7bcb18/4DNFI9TW5LR8.fastq.gz", "status": "released", "file_type_detailed": "reads (fastq)", "dbxrefs": ["SRA:SRR1658814"], "@id": "/files-fastq/4DNFI9TW5LR8/", "accession": "4DNFI9TW5LR8", "file_classification": "raw file", "uuid": "58c8e297-2396-404d-973f-3cfa7c7bcb18", "paired_end": "2", "file_size": 43847018, "file_type": "reads", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "file_format": {"uuid": "c13d06cf-218e-4f61-aaf0-91f226248b2c", "display_title": "fastq", "status": "released", "file_format": "fastq", "@id": "/file-formats/fastq/", "@type": ["FileFormat", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFI9TW5LR8/fastqc_report.html", "display_title": "QualityMetricFastqc from 2017-08-11", "uuid": "c1007dc3-d006-42db-b540-a92b852bd486", "overall_quality_status": "PASS", "@id": "/quality-metrics-fastqc/c1007dc3-d006-42db-b540-a92b852bd486/", "status": "released", "Total Sequences": 617683, "Sequence length": "95", "@type": ["QualityMetricFastqc", "QualityMetric", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "related_files": [{"relationship_type": "paired with", "file": {"file_type_detailed": "reads (fastq)", "@type": ["FileFastq", "File", "Item"], "file_type": "reads", "paired_end": "1", "accession": "4DNFIKVOAG6P", "uuid": "f7ede7ed-a440-47ec-b681-b742bb635f48", "@id": "/files-fastq/4DNFIKVOAG6P/", "status": "released", "display_title": "4DNFIKVOAG6P.fastq.gz", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "external_references": [{"ref": "SRA:SRR1658814", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRR1658814"}]}], "status": "released", "aliases": ["erezlab:hic186"], "dbxrefs": ["SRA:SRX765117", "GEO:GSM1551731"], "protocol": {"status": "released", "@type": ["Protocol", "Item"], "@id": "/protocols/692f7810-e44b-4c1b-9e1d-a79cd9998ef2/", "uuid": "692f7810-e44b-4c1b-9e1d-a79cd9998ef2", "display_title": "InsituHiC.pdf", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNEX44V7TZG", "biosample": {"accession": "4DNBSWIMEGHA", "status": "released", "biosample_type": "immortalized cells", "treatments_summary": "None", "modifications_summary": "None", "@type": ["Biosample", "Item"], "biosource_summary": "GM12878", "uuid": "2086f60f-ce1a-4d88-a770-7f9eaf7c253d", "display_title": "4DNBSWIMEGHA", "@id": "/biosamples/4DNBSWIMEGHA/", "biosource": [{"lab": {"display_title": "4DN DCIC, HMS", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "url": "https://catalog.coriell.org/0/Sections/Search/Sample_Detail.aspx?Ref=GM12878&Product=CC", "award": {"uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@id": "/awards/1U01CA200059-01/", "status": "current", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@type": ["Award", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "tissue": {"@type": ["OntologyTerm", "Item"], "uuid": "0c98ef0b-9a03-43f3-b409-fb091e62e2f8", "term_name": "lymphocyte of B lineage", "@id": "/ontology-terms/CL:0000945/", "display_title": "B-lymphocyte", "slim_terms": [{"status": "released", "@id": "/ontology-terms/CL:0000000/", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "released", "@id": "/ontology-terms/UBERON:0002405/", "display_title": "immune system", "@type": ["OntologyTerm", "Item"], "uuid": "111133bc-8535-4448-903e-854af460a233", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "current", "@id": "/ontology-terms/GO:0005623/", "display_title": "cell", "@type": ["OntologyTerm", "Item"], "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "preferred_name": "B-lymphocyte", "term_id": "CL:0000945", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "aliases": ["dcic:gm12878", "4dn-dcic-lab:gm12878"], "accession": "4DNSRVWZS4XO", "cell_line": {"uuid": "b9668b9a-be39-47de-8eab-5bf1b0854417", "term_name": "GM12878", "slim_terms": [{"status": "current", "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "display_title": "cell", "@id": "/ontology-terms/GO:0005623/", "@type": ["OntologyTerm", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "released", "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "display_title": "cell", "@id": "/ontology-terms/CL:0000000/", "@type": ["OntologyTerm", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "term_id": "EFO:0002784", "@id": "/ontology-terms/EFO:0002784/", "preferred_name": "GM12878", "display_title": "GM12878", "@type": ["OntologyTerm", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "individual": {"@type": ["IndividualHuman", "Individual", "Item"], "status": "released", "uuid": "3ec2ff42-6f8c-42e9-a1f0-0fa69f482b85", "display_title": "4DNINGWYEI15", "@id": "/individuals-human/4DNINGWYEI15/", "protected_data": false, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "references": [], "description": "Homo sapiens\u00a0GM12878 immortalized cell line", "date_created": "2017-04-09T17:24:19.894425+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2019-06-04T21:02:03.442329+00:00"}, "modifications": [], "biosource_type": "immortalized cell line", "cell_line_tier": "Unclassified", "public_release": "2017-07-20", "schema_version": "2", "project_release": "2017-07-20", "biosource_vendor": {"display_title": "Coriell Institute for Medical Research", "uuid": "f0e9a370-7451-40e3-9a35-c36d77ebdb4b", "status": "released", "@type": ["Vendor", "Item"], "@id": "/vendors/coriell-institute-for-medical-research/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "alternate_accessions": [], "@id": "/biosources/4DNSRVWZS4XO/", "@type": ["Biosource", "Item"], "uuid": "0f011b1e-b772-4f2a-8c24-cc55de28a994", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "GM12878 - 4DNSRVWZS4XO", "external_references": [], "biosource_name": "GM12878", "biosource_category": ["GM12878", "1000 genomes/Hap Map"], "organism": {"@id": "/organisms/9606/", "@type": ["Organism", "Item"], "uuid": "7745b647-ff15-4ff3-9ced-b897d4e2983c", "display_title": "H. sapiens", "status": "released", "name": "human", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "modifications": [], "treatments": [], "badges": [{"messages": ["Biosample missing Cell Culture Details"], "badge": {"badge_icon": "/static/img/badges/biosample-icon.svg", "@type": ["Badge", "Item"], "display_title": "Biosample Metadata Incomplete", "title": "Biosample Metadata Incomplete", "badge_classification": "Warning", "warning": "Biosample Metadata Incomplete", "@id": "/badges/biosample-metadata-incomplete/", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group.", "status": "released", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "documents": [], "references": [], "sop_mapping": {"has_sop": "No"}, "date_created": "2017-04-09T17:34:29.705843+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-07-03T15:02:20.235601+00:00"}, "ligation_time": 240.0, "digestion_time": 120.0, "public_release": "2017-04-09", "schema_version": "2", "tagging_method": "bio-dUTP (Tri-Link)", "experiment_type": {"uuid": "a2920a38-cdba-4ff0-b4f0-c6bb53257747", "display_title": "in situ Hi-C", "assay_subclass_short": "Hi-C", "@id": "/experiment-types/in-situ-hi-c/", "@type": ["ExperimentType", "Item"], "experiment_category": "Sequencing", "title": "in situ Hi-C", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "ligation_volume": 1.2, "processed_files": [{"open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/e616a9fc-a102-4dd7-8435-375abf32438e/4DNFIZDK8OUI.bam", "upload_key": "e616a9fc-a102-4dd7-8435-375abf32438e/4DNFIZDK8OUI.bam", "file_size": 124593073, "uuid": "e616a9fc-a102-4dd7-8435-375abf32438e", "file_format": {"status": "released", "@type": ["FileFormat", "Item"], "uuid": "d13d06cf-218e-4f61-aaf0-91f226248b3c", "file_format": "bam", "@id": "/file-formats/bam/", "display_title": "bam", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNFIZDK8OUI", "display_title": "4DNFIZDK8OUI.bam", "file_classification": "processed file", "href": "/files-processed/4DNFIZDK8OUI/@@download/4DNFIZDK8OUI.bam", "@id": "/files-processed/4DNFIZDK8OUI/", "status": "released", "@type": ["FileProcessed", "File", "Item"], "file_type_detailed": "alignments (bam)", "file_type": "alignments", "quality_metric": {"display_title": "QualityMetricBamqc from 2019-12-11", "@type": ["QualityMetricBamqc", "QualityMetric", "Item"], "overall_quality_status": "PASS", "status": "released", "@id": "/quality-metrics-bamqc/5b98a09f-f83d-4603-a995-6e87b587a5d7/", "uuid": "5b98a09f-f83d-4603-a995-6e87b587a5d7", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "quality_metric_summary": [{"title": "Total Reads", "value": "617683", "numberType": "integer"}, {"title": "Unmapped Reads", "value": "7.153", "tooltip": "Percent of total reads (=0.04m)", "numberType": "percent"}, {"title": "Multimapped Reads", "value": "15.376", "tooltip": "Percent of total reads (=0.09m)", "numberType": "percent"}, {"title": "Duplicate Reads", "value": "0.115", "tooltip": "Percent of total reads (=0.0m)", "numberType": "percent"}, {"title": "Walks", "value": "3.969", "tooltip": "Percent of total reads (=0.02m)", "numberType": "percent"}, {"title": "Minor Contigs", "value": "0.457", "tooltip": "Percent of total reads (=0.0m)", "numberType": "percent"}]}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "track_and_facet_info": {"experimental_lab": "Erez Lieberman Aiden, BCM", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "MboI", "dataset": "Hi-C on GM12878 cells - protocol variations", "condition": "in situ Hi-C on GM12878 with MboI and bio-dUTP (Tri-Link)", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "GM12878", "lab_name": "4DN DCIC, HMS"}, "external_references": []}, {"open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/4a0e9b36-e8b7-45a6-8c29-13bd6e4ab6ab/4DNFIOLKLN31.pairs.gz", "upload_key": "4a0e9b36-e8b7-45a6-8c29-13bd6e4ab6ab/4DNFIOLKLN31.pairs.gz", "file_size": 6994844, "uuid": "4a0e9b36-e8b7-45a6-8c29-13bd6e4ab6ab", "file_format": {"status": "released", "@type": ["FileFormat", "Item"], "uuid": "d13d06cf-218e-4f61-aaf0-91f226248b2c", "file_format": "pairs", "@id": "/file-formats/pairs/", "display_title": "pairs", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNFIOLKLN31", "display_title": "4DNFIOLKLN31.pairs.gz", "file_classification": "processed file", "href": "/files-processed/4DNFIOLKLN31/@@download/4DNFIOLKLN31.pairs.gz", "@id": "/files-processed/4DNFIOLKLN31/", "status": "released", "@type": ["FileProcessed", "File", "Item"], "file_type_detailed": "contact list-replicate (pairs)", "file_type": "contact list-replicate", "quality_metric": {"url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIOLKLN31/pairsqc_report.html", "Total reads": 453301, "display_title": "QualityMetricPairsqc from 2019-11-14", "@type": ["QualityMetricPairsqc", "QualityMetric", "Item"], "overall_quality_status": "PASS", "status": "released", "@id": "/quality-metrics-pairsqc/88e8dbb0-d059-45b0-9ca6-4e8beb28a5f9/", "uuid": "88e8dbb0-d059-45b0-9ca6-4e8beb28a5f9", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "quality_metric_summary": [{"title": "Filtered Reads", "value": "453301", "numberType": "integer"}, {"title": "Cis reads (>20kb)", "value": "23.242", "tooltip": "Percent of filtered reads (=0.11m)", "numberType": "percent"}, {"title": "Short cis reads", "value": "33.752", "tooltip": "Percent of filtered reads (=0.15m)", "numberType": "percent"}, {"title": "Trans Reads", "value": "43.006", "tooltip": "Percent of filtered reads (=0.19m)", "numberType": "percent"}]}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "track_and_facet_info": {"experimental_lab": "Erez Lieberman Aiden, BCM", "experiment_type": "in situ Hi-C", "experiment_bucket": "processed file", "assay_info": "MboI", "dataset": "Hi-C on GM12878 cells - protocol variations", "condition": "in situ Hi-C on GM12878 with MboI and bio-dUTP (Tri-Link)", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "GM12878", "lab_name": "4DN DCIC, HMS"}, "external_references": []}], "project_release": "2017-04-09", "digestion_enzyme": {"name": "MboI", "display_title": "MboI", "@type": ["Enzyme", "Item"], "@id": "/enzymes/MboI/", "uuid": "d8da42d0-bc20-40e5-bacf-c263b8603e03", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "crosslinking_time": 10.0, "crosslinking_method": "1% Formaldehyde", "alternate_accessions": [], "fragmentation_method": "sonication", "ligation_temperature": 25.0, "digestion_temperature": 37.0, "other_processed_files": [{"type": "preliminary", "files": [{"@type": ["FileProcessed", "File", "Item"], "display_title": "4DNFIXS4XUYP.bam", "file_size": 124857038, "accession": "4DNFIXS4XUYP", "file_type_detailed": "alignments (bam)", "file_type": "alignments", "@id": "/files-processed/4DNFIXS4XUYP/", "href": "/files-processed/4DNFIXS4XUYP/@@download/4DNFIXS4XUYP.bam", "status": "released", "uuid": "795a8175-d5af-40fb-a8a3-33e0e4af98af", "genome_assembly": "GRCh38", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/795a8175-d5af-40fb-a8a3-33e0e4af98af/4DNFIXS4XUYP.bam", "last_modified": {"date_modified": "2025-02-20T18:22:47.078468+00:00"}, "file_format": {"@type": ["FileFormat", "Item"], "display_title": "bam", "file_format": "bam", "status": "released", "@id": "/file-formats/bam/", "uuid": "d13d06cf-218e-4f61-aaf0-91f226248b3c", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "track_and_facet_info": {"experimental_lab": "Erez Lieberman Aiden, BCM", "experiment_type": "in situ Hi-C", "experiment_bucket": "HiC Processing Pipeline - v0.3.0", "assay_info": "MboI", "dataset": "Hi-C on GM12878 cells - protocol variations", "condition": "in situ Hi-C on GM12878 with MboI and bio-dUTP (Tri-Link)", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "GM12878", "lab_name": "4DN DCIC, HMS"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["FileProcessed", "File", "Item"], "display_title": "4DNFIQKQ43EC.pairs.gz", "file_size": 7089415, "accession": "4DNFIQKQ43EC", "file_type_detailed": "contact list-replicate (pairs)", "file_type": "contact list-replicate", "@id": "/files-processed/4DNFIQKQ43EC/", "href": "/files-processed/4DNFIQKQ43EC/@@download/4DNFIQKQ43EC.pairs.gz", "status": "released", "uuid": "14655335-799b-4ce8-9d93-7abc459e810a", "genome_assembly": "GRCh38", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/14655335-799b-4ce8-9d93-7abc459e810a/4DNFIQKQ43EC.pairs.gz", "last_modified": {"date_modified": "2025-02-20T18:22:42.354098+00:00"}, "file_format": {"@type": ["FileFormat", "Item"], "display_title": "pairs", "file_format": "pairs", "status": "released", "@id": "/file-formats/pairs/", "uuid": "d13d06cf-218e-4f61-aaf0-91f226248b2c", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "quality_metric": {"overall_quality_status": "PASS", "@id": "/quality-metrics-pairsqc/bae85727-8356-4134-a651-6868a4a45619/", "uuid": "bae85727-8356-4134-a651-6868a4a45619", "url": "https://s3.amazonaws.com/elasticbeanstalk-fourfront-webprod-wfoutput/4DNFIQKQ43EC/pairsqc_report.html", "@type": ["QualityMetricPairsqc", "QualityMetric", "Item"], "status": "released", "display_title": "QualityMetricPairsqc from 2024-07-02", "quality_metric_summary": [{"title": "Filtered Reads", "value": "467587", "numberType": "integer"}, {"title": "Cis reads (>20kb)", "value": "23.203", "tooltip": "Percent of filtered reads (=0.11m)", "numberType": "percent"}, {"title": "Short cis reads", "value": "32.795", "tooltip": "Percent of filtered reads (=0.15m)", "numberType": "percent"}, {"title": "Trans Reads", "value": "44.002", "tooltip": "Percent of filtered reads (=0.21m)", "numberType": "percent"}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "track_and_facet_info": {"experimental_lab": "Erez Lieberman Aiden, BCM", "experiment_type": "in situ Hi-C", "experiment_bucket": "HiC Processing Pipeline - v0.3.0", "assay_info": "MboI", "dataset": "Hi-C on GM12878 cells - protocol variations", "condition": "in situ Hi-C on GM12878 with MboI and bio-dUTP (Tri-Link)", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "GM12878", "lab_name": "4DN DCIC, HMS"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "title": "HiC Processing Pipeline - v0.3.0", "description": "These are files generated using the updated Hi-C processing pipeline. They should be largely similar to those available in the Processed Files tab, which were generated with the previous version of the standard pipeline.  One potential difference of note is that the version of cooler used to generate the mcool file has a bug fix to prevent a pixel duplication issue which is observed in some files generated by the previous version of the pipeline.  Another notable difference is that a filter is applied to remove reads with MAPQ scores below 30 prior to mcool file generation."}], "crosslinking_temperature": 25.0, "fragment_size_selection_method": "SPRI beads", "@id": "/experiments-hi-c/4DNEX44V7TZG/", "@type": ["ExperimentHiC", "Experiment", "Item"], "uuid": "64267a2b-e99f-45b1-9f1a-6c9c4b617698", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "in situ Hi-C on GM12878 with MboI - 4DNEX44V7TZG", "external_references": [{"ref": "SRA:SRX765117", "uri": "https://www.ncbi.nlm.nih.gov/sra/?term=SRX765117"}, {"ref": "GEO:GSM1551731", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1551731"}], "experiment_sets": [{"status": "released", "accession": "4DNESJNPEKZD", "@id": "/experiment-set-replicates/4DNESJNPEKZD/", "uuid": "80abb6ed-f6c3-44be-92a9-45ced677c19a", "display_title": "4DNESJNPEKZD", "experimentset_type": "replicate", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "produced_in_pub": {"status": "current", "short_attribution": "Rao SS et al. (2014)", "display_title": "Rao SS et al. (2014) PMID:25497547", "@type": ["Publication", "Item"], "authors": ["Rao SS", "Huntley MH", "Durand NC", "Stamenova EK", "Bochkov ID", "Robinson JT", "Sanborn AL", "Machol I", "Omer AD", "Lander ES", "Aiden EL"], "@id": "/publications/cf0e49aa-173c-49d1-a7c7-22acbc83c064/", "uuid": "cf0e49aa-173c-49d1-a7c7-22acbc83c064", "date_published": "2014-12-11", "title": "A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.", "journal": "Cell", "abstract": "We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells,  contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify approximately 10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs \"facing\" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.", "ID": "PMID:25497547", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"date_published": "2014-12-11", "@type": ["Publication", "Item"], "uuid": "cf0e49aa-173c-49d1-a7c7-22acbc83c064", "ID": "PMID:25497547", "authors": ["Rao SS", "Huntley MH", "Durand NC", "Stamenova EK", "Bochkov ID", "Robinson JT", "Sanborn AL", "Machol I", "Omer AD", "Lander ES", "Aiden EL"], "abstract": "We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells,  contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify approximately 10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs \"facing\" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.", "short_attribution": "Rao SS et al. (2014)", "@id": "/publications/cf0e49aa-173c-49d1-a7c7-22acbc83c064/", "display_title": "Rao SS et al. (2014) PMID:25497547", "title": "A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.", "status": "current", "journal": "Cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"date_published": "2023-02-22", "@type": ["Publication", "Item"], "uuid": "10a8b77d-571e-4442-baf4-47a8bd0fca84", "ID": "PMID:36629266", "authors": ["Kariti H", "Feld T", "Kaplan N"], "abstract": "The Hi-C method has revolutionized the study of genome organization, yet  interpretation of Hi-C interaction frequency maps remains a major challenge.  Genomic compartments are a checkered Hi-C interaction pattern suggested to  represent the partitioning of the genome into two self-interacting states  associated with active and inactive chromatin. Based on a few elementary  mechanistic assumptions, we derive a generative probabilistic model of genomic  compartments, called deGeco. Testing our model, we find it can explain observed  Hi-C interaction maps in a highly robust manner, allowing accurate inference of  interaction probability maps from extremely sparse data without any training of  parameters. Taking advantage of the interpretability of the model parameters, we  then test hypotheses regarding the nature of genomic compartments. We find clear  evidence of multiple states, and that these states self-interact with different  affinities. We also find that the interaction rules of chromatin states differ  considerably within and between chromosomes. Inspecting the molecular  underpinnings of a four-state model, we show that a simple classifier can use  histone marks to predict the underlying states with 87% accuracy. Finally, we  observe instances of mixed-state loci and analyze these loci in single-cell Hi-C  maps, finding that mixing of states occurs mainly at the cell level.", "short_attribution": "Kariti H et al. (2023)", "@id": "/publications/10a8b77d-571e-4442-baf4-47a8bd0fca84/", "display_title": "Kariti H et al. (2023) PMID:36629266", "title": "Hypothesis-driven probabilistic modelling enables a principled perspective of  genomic compartments.", "status": "current", "journal": "Nucleic acids research", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Enzyme", "value": "MboI", "combined": "Enzyme: MboI"}, "experiment_summary": "in situ Hi-C on GM12878 with MboI", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSWIMEGHA/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}