{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:09:26Z","timestamp":1790096966151,"version":"4.0.1"},"reference-count":67,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62302007"],"award-info":[{"award-number":["62302007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["62302007"],"award-info":[{"award-number":["62302007"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Genome-wide association studies (GWASs) have identified numerous loci associated with Alzheimer\u2019s disease (AD), yet the effector genes and regulatory mechanisms underlying many of these associations remain unresolved. This challenge is particularly pronounced for non-coding variants, whose regulatory effects may extend over long genomic distances and cannot be reliably inferred from the nearest gene alone. Here, we developed an integrative computational framework that incorporates three-dimensional chromatin interactions, expression quantitative trait loci (eQTL), and sequence-level regulatory annotations to identify candidate effector genes at AD-associated loci. AD-associated lead single-nucleotide polymorphisms (SNPs) and variants in strong linkage disequilibrium were mapped to enhancer elements and promoter-interacting regions using publicly available Hi-C and promoter capture Hi-C data from the hippocampus and cerebral cortex. Hi-C-derived enhancer\u2013promoter relationships were inferred using PSYCHIC, whereas significant promoter-centered interactions from promoter capture Hi-C were used to connect variant-containing regions with candidate effector genes. The resulting SNP\u2013gene relationships were further evaluated using brain-relevant eQTL evidence and predicted allele-dependent alterations in transcription factor binding motifs. This integrative analysis identified 608 unique candidate regulatory target genes supported by spatial chromatin contacts and complementary regulatory evidence, including genes not necessarily assigned by conventional nearest-gene annotation. Functional enrichment analysis indicated that the prioritized genes were involved in biological processes relevant to AD pathophysiology. Detailed analyses of three representative SNP\u2013gene pairs, rs2373115\u2013NARS2, rs6656401\u2013CR1, and rs3776011\u2013ACSL6, further illustrated how chromatin interaction, expression-associated, and sequence-level evidence can be combined to formulate locus-specific regulatory hypotheses. These findings represent computationally inferred and associative regulatory relationships rather than experimentally validated causal effects. They provide a structured framework for refining post-GWAS interpretation of non-coding AD risk loci and prioritizing candidate targets for further experimental validation.<\/jats:p>","DOI":"10.3390\/ijms27188396","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Annotation of Alzheimer\u2019s Disease-Associated SNPs Based on Three-Dimensional Chromatin Structure"],"prefix":"10.3390","volume":"27","author":[{"given":"Haitao","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, School of Artificial Intelligence, Anhui University, 111 Jiulong Road, Economic and Technological Development Zone, Hefei 230601, China"},{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, School of Artificial Intelligence, Anhui University, 111 Jiulong Road, Economic and Technological Development Zone, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, School of Artificial Intelligence, Anhui University, 111 Jiulong Road, Economic and Technological Development Zone, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-7775","authenticated-orcid":false,"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D1001","DOI":"10.1093\/nar\/gkt1229","article-title":"The NHGRI GWAS Catalog, a Curated Resource of SNP-Trait Associations","volume":"42","author":"Welter","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of Published Genome-Wide Association Studies, Targeted Arrays and Summary Statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.ajhg.2013.10.012","article-title":"Beyond GWASs: Illuminating the Dark Road from Association to Function","volume":"93","author":"Edwards","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ng.3538","article-title":"Integration of Summary Data from GWAS and eQTL Studies Predicts Complex Trait Gene Targets","volume":"48","author":"Zhu","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6046","DOI":"10.1093\/nar\/gkw500","article-title":"How Far from the SNP May the Causative Genes Be?","volume":"44","author":"Brodie","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1056\/NEJMoa1502214","article-title":"FTO Obesity Variant Circuitry and Adipocyte Browning in Humans","volume":"373","author":"Claussnitzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature13138","article-title":"Obesity-Associated Variants within FTO Form Long-Range Functional Connections with IRX3","volume":"507","author":"Smemo","year":"2014","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41588-019-0472-1","article-title":"Mapping Cis-Regulatory Chromatin Contacts in Neural Cells Links Neuropsychiatric Disorder Risk Variants to Target Genes","volume":"51","author":"Song","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"La Cognata, V., Morello, G., and Cavallaro, S. (2021). Omics Data and Their Integrative Analysis to Support Stratified Medicine in Neurodegenerative Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094820"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00401-009-0536-x","article-title":"Synaptic Degeneration in Alzheimer\u2019s Disease","volume":"118","author":"Arendt","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000452256","article-title":"From Common to Rare Variants: The Genetic Component of Alzheimer Disease","volume":"81","author":"Nicolas","year":"2016","journal-title":"Hum. Hered."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tig.2016.10.008","article-title":"Mining the Unknown: Assigning Function to Noncoding Single Nucleotide Polymorphisms","volume":"33","author":"Nishizaki","year":"2017","journal-title":"Trends Genet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McGovern, A., Schoenfelder, S., Martin, P., Massey, J., Duffus, K., Plant, D., Yarwood, A., Pratt, A.G., Anderson, A.E., and Isaacs, J.D. (2016). Capture Hi-C Identifies a Novel Causal Gene, IL20RA, in the Pan-Autoimmune Genetic Susceptibility Region 6q23. Genome Biol., 17.","DOI":"10.1186\/s13059-016-1078-x"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1091\/mbc.e16-12-0870","article-title":"HiHiMap: Single-Cell Quantitation of Histones and Histone Posttranslational Modifications across the Cell Cycle by High-Throughput Imaging","volume":"28","author":"Zane","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2010.12.002","article-title":"Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells","volume":"143","author":"Huang","year":"2010","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.1067799","article-title":"Capturing Chromosome Conformation","volume":"295","author":"Dekker","year":"2002","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1126\/science.1181369","article-title":"Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome","volume":"326","author":"Williams","year":"2009","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/ng.2871","article-title":"Analysis of Hundreds of Cis-Regulatory Landscapes at High Resolution in a Single, High-Throughput Experiment","volume":"46","author":"Hughes","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/ng.3286","article-title":"Mapping Long-Range Promoter Contacts in Human Cells with High-Resolution Capture Hi-C","volume":"47","author":"Mifsud","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1101\/gr.185272.114","article-title":"The Pluripotent Regulatory Circuitry Connecting Promoters to Their Long-Range Interacting Elements","volume":"25","author":"Schoenfelder","year":"2015","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/s41467-018-03411-9","article-title":"Capture Hi-C Identifies Putative Target Genes at 33 Breast Cancer Risk Loci","volume":"9","author":"Baxter","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/s41588-018-0211-z","article-title":"Promoter Capture Hi-C-Based Identification of Recurrent Noncoding Mutations in Colorectal Cancer","volume":"50","author":"Orlando","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41593-020-0603-0","article-title":"A Computational Tool (H-MAGMA) for Improved Prediction of Brain-Disorder Risk Genes by Incorporating Brain Chromatin Interaction Profiles","volume":"23","author":"Sey","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41597-023-01948-z","article-title":"Three-Dimensional Chromatin Architecture Datasets for Aging and Alzheimer\u2019s Disease","volume":"10","author":"Meng","year":"2023","journal-title":"Sci. Data"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106192","DOI":"10.1016\/j.nbd.2023.106192","article-title":"Epigenomic Analysis of Alzheimer\u2019s Disease Brains Reveals Diminished CTCF Binding on Genes Involved in Synaptic Organization","volume":"184","author":"Patel","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.jalz.2019.04.014","article-title":"Bioinformatics Strategy to Advance the Interpretation of Alzheimer\u2019s Disease GWAS Discoveries: The Roads from Association to Causation","volume":"15","author":"Lutz","year":"2019","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","article-title":"Alzheimer\u2019s Disease","volume":"377","author":"Ballard","year":"2011","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1038\/s41467-017-02386-3","article-title":"Promoter-Enhancer Interactions Identified from Hi-C Data Using Probabilistic Models and Hierarchical Topological Domains","volume":"8","author":"Ron","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.celrep.2016.10.061","article-title":"A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome","volume":"17","author":"Schmitt","year":"2016","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1038\/s41588-019-0494-8","article-title":"A Compendium of Promoter-Centered Long-Range Chromatin Interactions in the Human Genome","volume":"51","author":"Jung","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-Cell Transcriptomic Analysis of Alzheimer\u2019s Disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D833","DOI":"10.1093\/nar\/gkw943","article-title":"DisGeNET: A Comprehensive Platform Integrating Information on Human Disease-Associated Genes and Variants","volume":"45","author":"Bravo","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/ng1007-1181","article-title":"The NCBI dbGaP Database of Genotypes and Phenotypes","volume":"39","author":"Mailman","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer\u2019s Disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.neuron.2007.05.022","article-title":"GAB2 Alleles Modify Alzheimer\u2019s Risk in APOE \u03b54 Carriers","volume":"54","author":"Reiman","year":"2007","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s12031-018-1144-9","article-title":"Alzheimer\u2019s Disease Risk Variant Rs2373115 Regulates GAB2 and NARS2 Expression in Human Brain Tissues","volume":"66","author":"Liu","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-Wide Association Study Identifies Variants at CLU and PICALM Associated with Alzheimer\u2019s Disease","volume":"41","author":"Harold","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ng.439","article-title":"Genome-Wide Association Study Identifies Variants at CLU and CR1 Associated with Alzheimer\u2019s Disease","volume":"41","author":"Lambert","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/imcb.12301","article-title":"The Role of Innate Immune Responses and Neuroinflammation in Amyloid Accumulation and Progression of Alzheimer\u2019s Disease","volume":"98","author":"Webers","year":"2020","journal-title":"Immunol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ana.22277","article-title":"CR1 Is Associated with Amyloid Plaque Burden and Age-Related Cognitive Decline","volume":"69","author":"Chibnik","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2011.12.059","article-title":"Alzheimer\u2019s Disease Risk Factor Complement Receptor 1 Is Associated with Depression","volume":"510","author":"Hamilton","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e004","DOI":"10.1621\/nrs.06004","article-title":"The BRG1 Transcriptional Coregulator","volume":"6","author":"Trotter","year":"2008","journal-title":"Nucl. Recept. Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1080\/19491034.2016.1276145","article-title":"The Connection between BRG1, CTCF and Topoisomerases at TAD Boundaries","volume":"8","author":"Barutcu","year":"2017","journal-title":"Nucleus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1073\/pnas.0806420106","article-title":"BRG1 Requirement for Long-Range Interaction of a Locus Control Region with a Downstream Promoter","volume":"106","author":"Kim","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/mp.2015.23","article-title":"A Novel Alzheimer Disease Locus Located near the Gene Encoding Tau Protein","volume":"21","author":"Jun","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12525","DOI":"10.1073\/pnas.1807958115","article-title":"Acyl-CoA Synthetase 6 Enriches the Neuroprotective Omega-3 Fatty Acid DHA in the Brain","volume":"115","author":"Fernandez","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Li, M.D., Burns, T.C., Morgan, A.A., and Khatri, P. (2014). Integrated Multi-Cohort Transcriptional Meta-Analysis of Neurodegenerative Diseases. Acta Neuropathol. Commun., 2.","DOI":"10.1186\/s40478-014-0093-y"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e144351","DOI":"10.1172\/jci.insight.144351","article-title":"Acyl-CoA Synthetase 6 Is Required for Brain Docosahexaenoic Acid Retention and Neuroprotection during Aging","volume":"6","author":"Fernandez","year":"2021","journal-title":"JCI Insight"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jalz.2013.12.024","article-title":"Resolution of Inflammation Is Altered in Alzheimer\u2019s Disease","volume":"11","author":"Wang","year":"2015","journal-title":"Alzheimers Dement"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1800242024","DOI":"10.1523\/JNEUROSCI.1800-24.2024","article-title":"Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer\u2019s Disease","volume":"45","author":"Dunn","year":"2025","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Konno, D., Iwashita, M., Satoh, Y., Momiyama, A., Abe, T., Kiyonari, H., and Matsuzaki, F. (2012). The Mammalian DM Domain Transcription Factor Dmrta2 Is Required for Early Embryonic Development of the Cerebral Cortex. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046577"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hu, Y.-S., Xin, J., Hu, Y., Zhang, L., and Wang, J. (2017). Analyzing the Genes Related to Alzheimer\u2019s Disease via a Network and Pathway-Based Approach. Alzheimer\u2019s Res. Ther., 9.","DOI":"10.1186\/s13195-017-0252-z"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"224","DOI":"10.14283\/jpad.2020.65","article-title":"Molecular Subtyping of Mild Cognitive Impairment Based on Genetic Polymorphism and Gene Expression","volume":"8","author":"Li","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D877","DOI":"10.1093\/nar\/gkv1340","article-title":"HaploReg v4: Systematic Mining of Putative Causal Variants, Cell Types, Regulators and Target Genes for Human Complex Traits and Disease","volume":"44","author":"Ward","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Servant, N., Varoquaux, N., Lajoie, B.R., Viara, E., Chen, C.-J., Vert, J.-P., Heard, E., Dekker, J., and Barillot, E. (2015). HiC-Pro: An Optimized and Flexible Pipeline for Hi-C Data Processing. Genome Biol., 16.","DOI":"10.1186\/s13059-015-0831-x"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.2354","article-title":"Fast and Accurate Genotype Imputation in Genome-Wide Association Studies through Pre-Phasing","volume":"44","author":"Howie","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nature14222","article-title":"Chromatin Architecture Reorganization during Stem Cell Differentiation","volume":"518","author":"Dixon","year":"2015","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/nmeth.2148","article-title":"Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization","volume":"9","author":"Imakaev","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1038\/nprot.2017.124","article-title":"Chromatin-State Discovery and Genome Annotation with ChromHMM","volume":"12","author":"Ernst","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nmeth.1906","article-title":"ChromHMM: Automating Chromatin-State Discovery and Characterization","volume":"9","author":"Ernst","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for Gene List Enrichment Analysis and Candidate Gene Prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1257601","DOI":"10.1126\/science.1257601","article-title":"Uncovering Disease-Disease Relationships through the Incomplete Interactome","volume":"347","author":"Menche","year":"2015","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"The GTEx Consortium, Ardlie, K.G., Deluca, D.S., Segr\u00e8, A.V., Sullivan, T.J., Young, T.R., Gelfand, E.T., Trowbridge, C.A., Maller, J.B., and Tukiainen, T. (2015). The Genotype-Tissue Expression (GTEx) Pilot Analysis: Multitissue Gene Regulation in Humans. Science, 348, 648\u2013660.","DOI":"10.1126\/science.1262110"},{"key":"ref_66","first-page":"D87","article-title":"JASPAR 2020: Update of the Open-Access Database of Transcription Factor Binding Profiles","volume":"48","author":"Fornes","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pro.3307","article-title":"The Human Protein Atlas: A Spatial Map of the Human Proteome","volume":"27","author":"Thul","year":"2018","journal-title":"Protein Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:35:51Z","timestamp":1790094951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":67,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188396"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188396","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}