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While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. Our highly collaborative team will draw on the diverse experiences of its members to provide a synergistic environment to push the limits of our understanding of nuclear structure. 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As 4DN does **not** host the genome assembly for this organism, this bed file cannot be visualized using HiGlass tool. However, users can download HiGlass tool from [**here**](https://higlass.io) for visualization purposes. While visualizing file through HiGlass please note that peaks of a specific cell type are represented using different track colors. Additionally, a zipped folder containing individual bed files specific for each cell type is also provided. The information on track colors and associated cell type can be accessed via a key file [**here**](https://data.4dnucleome.org/documents/42b3f69f-7bf7-458d-9c4b-2b0d53636c6c/)", "name": "supp_file_peaks_noref", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE II", "@id": "/awards/2U01CA200059-06/", "@type": ["Award", "Item"], "status": "current", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Aggregated non-redundant peaks - NoRef", "status": "released", "aliases": ["4dn-dcic-lab:peak_bed_file_noref"], "options": {"filetype": "md", "collapsible": false, "default_open": true, "convert_ext_links": true}, "date_created": "2024-08-26T15:08:02.349438+00:00", "section_type": "Page Section", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-09-23T17:00:51.151860+00:00"}, "schema_version": "2", "@id": "/static-sections/84937aec-9a2a-4031-b0ea-caedd83942cc/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "84937aec-9a2a-4031-b0ea-caedd83942cc", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.6f9809b1-b9b4-4f2f-8e6d-0762bce320ef"]}, "display_title": "Aggregated non-redundant peaks - NoRef", "external_references": [], "content": "**NOTE** Non-redundant peaks aggregated from multiple donors in bed format is provided as a supplementary file. 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However, users can download HiGlass tool from <a href=\"https://higlass.io\" rel=\"noopener noreferrer\" target=\"_blank\"><strong>here</strong></a> for visualization purposes. While visualizing file through HiGlass please note that peaks of a specific cell type are represented using different track colors. Additionally, a zipped folder containing individual bed files specific for each cell type is also provided. 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We find that  conserved and divergent gene regulatory features are reflected in the evolution  of the three-dimensional genome. Transposable elements contribute to nearly 80%  of the human-specific candidate cis-regulatory elements in cortical cells.  Through machine learning, we develop sequence-based predictors of candidate  cis-regulatory elements in different species and demonstrate that the genomic  regulatory syntax is highly preserved from rodents to primates. Finally, we show  that epigenetic conservation combined with sequence similarity helps to uncover  functional cis-regulatory elements and enhances our ability to interpret genetic  variants contributing to neurological disease and traits.", "uuid": "8d4e8d7c-b98f-4857-a4c1-274dfc39817a", "status": "current", "ID": "PMID:38092918", "journal": "Nature", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"status": "current", "@id": "/publications/8d4e8d7c-b98f-4857-a4c1-274dfc39817a/", "title": "Conserved and divergent gene regulatory programs of the mammalian neocortex.", "ID": "PMID:38092918", "abstract": "Divergence of cis-regulatory elements drives species-specific traits(1), but how  this manifests in the evolution of the neocortex at the molecular and cellular  level remains unclear. Here we investigated the gene regulatory programs in the  primary motor cortex of human, macaque, marmoset and mouse using single-cell  multiomics assays, generating gene expression, chromatin accessibility, DNA  methylome and chromosomal conformation profiles from a total of over 200,000  cells. From these data, we show evidence that divergence of transcription factor  expression corresponds to species-specific epigenome landscapes. We find that  conserved and divergent gene regulatory features are reflected in the evolution  of the three-dimensional genome. Transposable elements contribute to nearly 80%  of the human-specific candidate cis-regulatory elements in cortical cells.  Through machine learning, we develop sequence-based predictors of candidate  cis-regulatory elements in different species and demonstrate that the genomic  regulatory syntax is highly preserved from rodents to primates. Finally, we show  that epigenetic conservation combined with sequence similarity helps to uncover  functional cis-regulatory elements and enhances our ability to interpret genetic  variants contributing to neurological disease and traits.", "uuid": "8d4e8d7c-b98f-4857-a4c1-274dfc39817a", "display_title": "Zemke NR et al. (2023) PMID:38092918", "journal": "Nature", "authors": ["Zemke NR", "Armand EJ", "Wang W", "Lee S", "Zhou J", "Li YE", "Liu H", "Tian W", "Nery JR", "Castanon RG", "Bartlett A", "Osteen JK", "Li D", "Zhuo X", "Xu V", "Chang L", "Dong K", "Indralingam HS", "Rink JA", "Xie Y", "Miller M", "Krienen FM", "Zhang Q", "Taskin N", "Ting J", "Feng G", "McCarroll SA", "Callaway EM", "Wang T", "Lein ES", "Behrens MM", "Ecker JR", "Ren B"], "date_published": "2023-12", "@type": ["Publication", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 1, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/experiment-set-replicates/4DNES5LUN5GF/", "embedded_path": "badges", "item": {"messages": ["Replicate set contains only a single biological replicate"], "badge": {"commendation": null, "warning": "Replicate Numbers", "uuid": "24a64a84-3c33-4d76-aaf2-e5ef45eff347", "@id": "/badges/replicate-numbers/", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "description": "Issues with replicate numbers"}}}]}, "validation-errors": []}