{"id":{"repo_id":"uic","oai_identifier":"oai:figshare.com:article/31451299"},"canonical_url":"https://search.dev.ndltd.org/etd/uic/oai:figshare.com:article/31451299","repository":{"repo_id":"uic","name":"University of Illinois - Chicago","base_url":"https://api.figshare.com/v2/oai"},"display":{"title":"3D Chromatin Structure and Gene Regulation: Integrated Genome Structure, Transcriptomics and Epigenetics","abstract":"The three-dimensional (3D) organization of the genome is essential for regulating gene expression, replication, and stability. Chromatin folding mediates enhancer–promoter communication, but bulk Hi-C data obscure single-cell variability, while sparse single-cell Hi-C limits structural resolution. This dissertation develops computational approaches to reconstruct single-cell chromatin conformations, integrate them with functional genomics, and make them broadly accessible. I present a framework that combines Hi-C with expression quantitative trait loci (eQTL) data to identify statistically significant contacts and reconstruct ensembles of single-cell structures. These analyses reveal that spatial proximity between eQTL–eGene pairs enhances regulatory effects and that many-body interactions underpin tissue-specific expression. To enable systematic exploration, I created ChromPolymerDB, a high-resolution public database of ~10⁸ reconstructed chromatin structures at 5 kb resolution across 50 human cell types. With interactive visualization and multi-omics integration, ChromPolymerDB supports investigations of enhancer–promoter contacts, structural rewiring, and disease-associated remodeling. Finally, I demonstrate that FoldRec promoter–enhancer interactions strongly correlate with cell-type-specific expression and that chromatin heterogeneity gives rise to distinct structural subpopulations with different regulatory potential. Together, these advances provide methodological innovations, community resources, and biological insights into how genome architecture encodes regulatory logic at the single-cell level, laying foundations for studies in development, disease, and precision medicine.","abstract_html":"The three-dimensional (3D) organization of the genome is essential for regulating gene expression, replication, and stability. Chromatin folding mediates enhancer–promoter communication, but bulk Hi-C data obscure single-cell variability, while sparse single-cell Hi-C limits structural resolution. This dissertation develops computational approaches to reconstruct single-cell chromatin conformations, integrate them with functional genomics, and make them broadly accessible. I present a framework that combines Hi-C with expression quantitative trait loci (eQTL) data to identify statistically significant contacts and reconstruct ensembles of single-cell structures. These analyses reveal that spatial proximity between eQTL–eGene pairs enhances regulatory effects and that many-body interactions underpin tissue-specific expression. To enable systematic exploration, I created ChromPolymerDB, a high-resolution public database of ~10⁸ reconstructed chromatin structures at 5 kb resolution across 50 human cell types. With interactive visualization and multi-omics integration, ChromPolymerDB supports investigations of enhancer–promoter contacts, structural rewiring, and disease-associated remodeling. Finally, I demonstrate that FoldRec promoter–enhancer interactions strongly correlate with cell-type-specific expression and that chromatin heterogeneity gives rise to distinct structural subpopulations with different regulatory potential. Together, these advances provide methodological innovations, community resources, and biological insights into how genome architecture encodes regulatory logic at the single-cell level, laying foundations for studies in development, disease, and precision medicine.","abstract_has_math":false,"creators":["Lin Du (311554)"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-12-01T00:00:00Z","date_published":"2025-12-01T00:00:00Z","updated_at":"2026-07-27T21:34:24Z","subjects":["Biology","Bioinformatics"],"languages":[],"rights":["In Copyright"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.25417/uic.31451299.v1","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Lin Du (311554)"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-12-01T00:00:00Z"]},{"key":"dc:relation","label":"Dc Relation","values":["https://figshare.com/articles/thesis/3D_Chromatin_Structure_and_Gene_Regulation_Integrated_Genome_Structure_Transcriptomics_and_Epigenetics/31451299"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Bioinformatics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.25417/uic.31451299.v1"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The three-dimensional (3D) organization of the genome is essential for regulating gene expression, replication, and stability. Chromatin folding mediates enhancer–promoter communication, but bulk Hi-C data obscure single-cell variability, while sparse single-cell Hi-C limits structural resolution. This dissertation develops computational approaches to reconstruct single-cell chromatin conformations, integrate them with functional genomics, and make them broadly accessible. I present a framework that combines Hi-C with expression quantitative trait loci (eQTL) data to identify statistically significant contacts and reconstruct ensembles of single-cell structures. These analyses reveal that spatial proximity between eQTL–eGene pairs enhances regulatory effects and that many-body interactions underpin tissue-specific expression. To enable systematic exploration, I created ChromPolymerDB, a high-resolution public database of ~10⁸ reconstructed chromatin structures at 5 kb resolution across 50 human cell types. With interactive visualization and multi-omics integration, ChromPolymerDB supports investigations of enhancer–promoter contacts, structural rewiring, and disease-associated remodeling. Finally, I demonstrate that FoldRec promoter–enhancer interactions strongly correlate with cell-type-specific expression and that chromatin heterogeneity gives rise to distinct structural subpopulations with different regulatory potential. Together, these advances provide methodological innovations, community resources, and biological insights into how genome architecture encodes regulatory logic at the single-cell level, laying foundations for studies in development, disease, and precision medicine."]},{"key":"dc:title","label":"Title","values":["3D Chromatin Structure and Gene Regulation: Integrated Genome Structure, Transcriptomics and Epigenetics"]}]}],"canonical_facts":{"dc:creator":["Lin Du (311554)"],"dc:date":["2025-12-01T00:00:00Z"],"dc:description":["The three-dimensional (3D) organization of the genome is essential for regulating gene expression, replication, and stability. Chromatin folding mediates enhancer–promoter communication, but bulk Hi-C data obscure single-cell variability, while sparse single-cell Hi-C limits structural resolution. This dissertation develops computational approaches to reconstruct single-cell chromatin conformations, integrate them with functional genomics, and make them broadly accessible. I present a framework that combines Hi-C with expression quantitative trait loci (eQTL) data to identify statistically significant contacts and reconstruct ensembles of single-cell structures. These analyses reveal that spatial proximity between eQTL–eGene pairs enhances regulatory effects and that many-body interactions underpin tissue-specific expression. To enable systematic exploration, I created ChromPolymerDB, a high-resolution public database of ~10⁸ reconstructed chromatin structures at 5 kb resolution across 50 human cell types. With interactive visualization and multi-omics integration, ChromPolymerDB supports investigations of enhancer–promoter contacts, structural rewiring, and disease-associated remodeling. Finally, I demonstrate that FoldRec promoter–enhancer interactions strongly correlate with cell-type-specific expression and that chromatin heterogeneity gives rise to distinct structural subpopulations with different regulatory potential. Together, these advances provide methodological innovations, community resources, and biological insights into how genome architecture encodes regulatory logic at the single-cell level, laying foundations for studies in development, disease, and precision medicine."],"dc:identifier":["10.25417/uic.31451299.v1"],"dc:relation":["https://figshare.com/articles/thesis/3D_Chromatin_Structure_and_Gene_Regulation_Integrated_Genome_Structure_Transcriptomics_and_Epigenetics/31451299"],"dc:rights":["In Copyright"],"dc:subject":["Biology","Bioinformatics"],"dc:title":["3D Chromatin Structure and Gene Regulation: Integrated Genome Structure, Transcriptomics and Epigenetics"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T21:34:24Z"}