{"lab": {"display_title": "Mitchell Guttman, CALTECH", "title": "Mitchell Guttman, CALTECH", "uuid": "c17e88b5-912a-496a-acc7-28dd71215a7d", "@type": ["Lab", "Item"], "@id": "/labs/mitchell-guttman-lab/", "status": "current", "correspondence": [{"contact_email": "bWd1dHRtYW5AY2FsdGVjaC5lZHU=", "@id": "/users/ac3920c8-caa6-444b-be8a-48b52a1dcb3e/", "display_title": "Mitchell Guttman"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.c17e88b5-912a-496a-acc7-28dd71215a7d"]}}, "award": {"uuid": "4de1cf81-1ea0-4a19-bc7a-dd3343b34438", "center_title": "NBC - Guttman", "@id": "/awards/1U01DA040612-01/", "@type": ["Award", "Item"], "name": "1U01DA040612-01", "project": "4DN", "description": "NBC: The nucleus of each cell is a complex arrangement of DNA, RNA, and protein that is dynamically organized into various nuclear bodies and compartments that are often arranged around shared functional and regulatory roles. Yet, while many of these nuclear compartments were first identified several decades ago a major challenge with characterizing these compartments is that there are currently no biochemical methods for isolating individual nuclear compartments. Importantly, many nuclear bodies are marked and maintained by nuclear retained long non-coding RNAs (lncRNAs). Here we aim to develop several novel technologies to purify the molecular constituents of nuclear domains and their necessity and sufficiency in forming these compartments. Together these technologies will allow us to systematically address the following questions: Aim 1: What are the optimal biochemical conditions in which to specifically and accurately purify specific nuclear bodies and compartments in order to identify their DNA, RNA and protein components? A critical aspect of biochemical purifications is the fine balance between cross-linking conditions that identify direct molecular interactions while not over-crosslinking that could result in indirect interactions. Usin known nuclear compartments such as the nucleolus, nuclear speckles, and paraspeckles we will optimize RAP for isolating DNA-RNA, RNA-RNA, RNA-protein interactions. We aim to identify universally applicable purification conditions to identify molecular interactions within nuclear and other subcellular structures. Aim 2: What are the DNA, RNA and protein factors involved in nuclear compartments? Although most known nuclear bodies are characterized by lncRNAs the other RNA, DNA and protein factors remain less well defined. Here we will develop technologies to catalog the molecular factors that comprise various nuclear bodies. We will further validate these components through colocalization of these components within a nuclear domain using visualization approaches (e.g. RNA-DNA Co-FISH). Overall we aim to apply new technologies to systematic and comprehensive catalog of RNA, DNA and Proteins in nuclear bodies. Aim 3: Are lncRNAs and proteins necessary and/or sufficient for nuclear compartmentalization? Here we will develop a novel technology platform, termed CRISPR-Display, which allows long RNA cargos to be appended and delivered by CRISPR-Cas9 systems to a desired site in the genome. We will develop this technology to test if lncRNA molecules are sufficient to drive nuclear organization. We will also use CRISPR-Display to multiplex several RNA aptamers that can be used to recruit proteins (with reciprocal protein epitopes that bind RNA aptamers) and test if they are sufficient to form nuclear compartments. In parallel we will perform loss-of- function approaches to identify protein and or RNA components are required for establishing nuclear domains. Collectively our proposal aims to develop powerful and multifaceted technologies to catalog the molecular components of subnuclear structures, validate these interactions and test their biological importance.", "display_title": "DECIPHERING THE FUNCTION AND MECHANISMS OF LNCRNA-MEDIATED ORGANIZATION OF NUCLEAR COMPARTMENTS", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "md5sum": "8a1589cb2a4d6efa6b0638b4d737e150", "status": "released", "aliases": ["4dn-dcic-lab:human-sprite-mcool-2-1000"], "filename": "all_GRCh38_2-1000clusters_n2_5000.mcool", "accession": "4DNFIUOOYQC3", "file_size": 48278032236, "file_type": "contact matrix", "description": "mcool file generated from sprite clusters of size 2-1000 with 2/n cluster size normalization", "file_format": {"@type": ["FileFormat", "Item"], "uuid": "d13d06cf-218e-4f61-ccf0-91f226248b2c", "display_title": "mcool", "status": "released", "file_format": "mcool", "@id": "/file-formats/mcool/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "higlass_uid": "IVPFZ06uSAysusV4I8fEjw", "date_created": "2019-01-03T16:09:29.417788+00:00", "notes_to_tsv": ["This file contains processed results performed outside of the 4DN-DCIC standardized pipelines. The file and the information about its provenance, i.e. which files were used as input to generate this output was provided by or done in collaboration with the lab that did the experiments to generate the raw data. For more information about the specific analysis performed, please contact the submitting lab or refer to the relevant publication if available.", "WARNING - Due to a bug in the version of cooler (0.8.3) used in the current 4DN standard Hi-C processing pipeline some pixels may occur mulitple times at a single resolution with different counts being reported for each occurence.  This duplication does not affect the higlass display of these files, howevver, downstream analyses using this file may encounter issues due to this pixel duplication.  The counts from the duplicate pixels can be aggregated to determine the correct count value at that location. If this issue is problematic for your needs you should consider regenerating the matrices from the merged pairs file of the associated dataset using a more recent version of cooler.  We are working to update the pipeline but do not yet have a predicted date for when this issue will be resolved."], "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-08-25T17:54:41.478799+00:00"}, "produced_from": ["4dn-dcic-lab:all_GRCh38.clusters.gz"], "content_md5sum": "8a1589cb2a4d6efa6b0638b4d737e150", "public_release": "2019-02-15", "quality_metric": {"status": "released", "display_title": "QualityMetricMcool from 2021-05-21", "uuid": "fd6fdca1-803d-48ea-a32e-c1ca6948ecbb", "@type": ["QualityMetricMcool", "QualityMetric", "Item"], "@id": "/quality-metrics-mcool/fd6fdca1-803d-48ea-a32e-c1ca6948ecbb/", "quality_metric_summary": [{"title": "Failed Balancing", "value": "None", "tooltip": "Resolutions where balancing failed", "numberType": "string"}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "schema_version": "3", "static_content": [{"content": {"name": "58deab45-8b95-45a5-b98d-098da61ad160", "award": {"uuid": "4de1cf81-1ea0-4a19-bc7a-dd3343b34438", "display_title": "DECIPHERING THE FUNCTION AND MECHANISMS OF LNCRNA-MEDIATED ORGANIZATION OF NUCLEAR COMPARTMENTS", "status": "current", "@type": ["Award", "Item"], "@id": "/awards/1U01DA040612-01/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "4DNFIUOOYQC3 - contact matrix for GM12878 DNA SPRITE", "uuid": "58deab45-8b95-45a5-b98d-098da61ad160", "description": "", "status": "released", "display_title": "4DNFIUOOYQC3 - contact matrix for GM12878 DNA SPRITE", "contributing_labs": [], "@id": "/higlass-view-configs/58deab45-8b95-45a5-b98d-098da61ad160/", "@type": ["HiglassViewConfig", "UserContent", "Item"], "filetype": "HiglassViewConfig", "lab": {"status": "current", "display_title": "Mitchell Guttman, CALTECH", "@type": ["Lab", "Item"], "@id": "/labs/mitchell-guttman-lab/", "uuid": "c17e88b5-912a-496a-acc7-28dd71215a7d", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.c17e88b5-912a-496a-acc7-28dd71215a7d"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267307e3a"]}}, "location": "tab:higlass", "description": "auto_generated_higlass_view_config"}], "genome_assembly": "GRCh38", "project_release": "2019-02-15", "file_classification": "processed file", "@id": "/files-processed/4DNFIUOOYQC3/", "@type": ["FileProcessed", "File", "Item"], "uuid": "146e467e-6226-41b3-a286-fec72ea82eee", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "4DNFIUOOYQC3.mcool", "external_references": [], "experiments": [], "file_type_detailed": "contact matrix (mcool)", "track_and_facet_info": {"dataset": "DNA SPRITE on GM12878", "experimental_lab": "Mitchell Guttman, CALTECH", "replicate_info": "merged replicates", "experiment_bucket": "processed file", "experiment_type": "DNA SPRITE", "biosource_name": "GM12878", "lab_name": "Mitchell Guttman, CALTECH", "track_title": "contact matrix for GM12878 DNA SPRITE"}, "title": "4DNFIUOOYQC3", "href": "/files-processed/4DNFIUOOYQC3/@@download/4DNFIUOOYQC3.mcool", "upload_key": "146e467e-6226-41b3-a286-fec72ea82eee/4DNFIUOOYQC3.mcool", "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/146e467e-6226-41b3-a286-fec72ea82eee/4DNFIUOOYQC3.mcool", "tsv_notes": "This file contains processed results performed outside of the 4DN-DCIC standardized pipelines. The file and the information about its provenance, i.e. which files were used as input to generate this output was provided by or done in collaboration with the lab that did the experiments to generate the raw data. For more information about the specific analysis performed, please contact the submitting lab or refer to the relevant publication if available.,WARNING - Due to a bug in the version of cooler (0.8.3) used in the current 4DN standard Hi-C processing pipeline some pixels may occur mulitple times at a single resolution with different counts being reported for each occurence.  This duplication does not affect the higlass display of these files, howevver, downstream analyses using this file may encounter issues due to this pixel duplication.  The counts from the duplicate pixels can be aggregated to determine the correct count value at that location. If this issue is problematic for your needs you should consider regenerating the matrices from the merged pairs file of the associated dataset using a more recent version of cooler.  We are working to update the pipeline but do not yet have a predicted date for when this issue will be resolved.", "workflow_run_inputs": [{"@id": "/workflow-runs-awsem/675bbf90-25f6-4bc5-ae2a-c4e8320ba9fe/", "@type": ["WorkflowRunAwsem", "WorkflowRun", "Item"], "status": "released", "display_title": "mcoolQC v1 run 2021-05-21 04:57:08.085864", "uuid": "675bbf90-25f6-4bc5-ae2a-c4e8320ba9fe", "output_files": [{"workflow_argument_name": "mcool_qc", "value_qc": {"status": "released", "@id": "/quality-metrics-mcool/fd6fdca1-803d-48ea-a32e-c1ca6948ecbb/", "uuid": "fd6fdca1-803d-48ea-a32e-c1ca6948ecbb", "@type": ["QualityMetricMcool", "QualityMetric", "Item"], "overall_quality_status": "PASS", "display_title": "QualityMetricMcool from 2021-05-21", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "workflow": {"uuid": "0bf9f47a-dec1-4324-9b41-fa183880a7db", "display_title": "Quality metrics for mcool files - 4DNWFXKEC8OX", "title": "Quality metrics for mcool files", "@type": ["Workflow", "Item"], "status": "released", "@id": "/workflows/4DNWFXKEC8OX/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "input_files": [{"workflow_argument_name": "mcoolfile", "value": {"@type": ["FileProcessed", "File", "Item"], "accession": "4DNFIUOOYQC3", "status": "released", "@id": "/files-processed/4DNFIUOOYQC3/", "uuid": "146e467e-6226-41b3-a286-fec72ea82eee", "display_title": "4DNFIUOOYQC3.mcool", "filename": "all_GRCh38_2-1000clusters_n2_5000.mcool", "file_format": {"display_title": "mcool", "status": "released", "@type": ["FileFormat", "Item"], "uuid": "d13d06cf-218e-4f61-ccf0-91f226248b2c", "file_format": "mcool", "@id": "/file-formats/mcool/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"error": "no view permissions"}], "workflow_run_outputs": [], "experiment_sets": [{"@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESI1U7ZW9/", "status": "released", "display_title": "4DNESI1U7ZW9", "accession": "4DNESI1U7ZW9", "uuid": "cddd45d8-fbec-4806-a63b-6c16c5bd3138", "last_modified": {"date_modified": "2020-11-06T23:16:01.938810+00:00"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "source_experiment_sets": [{"@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "display_title": "4DNESI1U7ZW9", "@id": "/experiment-set-replicates/4DNESI1U7ZW9/", "status": "released", "uuid": "cddd45d8-fbec-4806-a63b-6c16c5bd3138", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@context": "/terms/", "aggregated-items": {"last_modified": [{"parent": "/files-processed/4DNFIUOOYQC3/", "embedded_path": "last_modified", "item": {"date_modified": "2023-08-25T17:54:41.478799+00:00"}}, {"parent": "/experiment-set-replicates/4DNESI1U7ZW9/", "embedded_path": "experiment_sets.last_modified", "item": {"date_modified": "2020-11-06T23:16:01.938810+00:00"}}]}, "validation-errors": []}