{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:03:05Z","timestamp":1789718585627,"version":"4.0.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Science and Technology","award":["2022ZD0115001"],"award-info":[{"award-number":["2022ZD0115001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92353304"],"award-info":[{"award-number":["92353304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2495221"],"award-info":[{"award-number":["T2495221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Cornerstone Science Foundation","award":["NCI202305"],"award-info":[{"award-number":["NCI202305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The non-coding genome operates through a complex, multiscale regulatory system where regulated gene expressions are closely associated with cell-type-specific histone modifications, transcription factor binding, and 3D conformation. Developing computational models that can integrate these patterns to predict and interpret the regulatory system remains challenging. Here, we present GenoME, a Mixture of Experts (MoE)-based generative model that uses DNA sequence and cell-type-specific ATAC-seq signals to predict a unified genomic profiles encompassing epigenomics, transcriptomics, and chromatin architecture at base-pair to kilobase resolutions. GenoME enables multiscale predictions for held-out genomic regions and, critically, generalizes to predict the full regulatory landscape of unseen or individualized cell types from a single ATAC-seq input. We equip GenoME with an in silico perturbation framework that accurately forecasts the multimodal consequences of genetic perturbations and identifies functional enhancer\u2013promoter connections, outperforming specialized models like Activity-by-Contact. These predictions can also be used to decipher the transcription factor grammar of cell-type-specific enhancers. GenoME thus provides a versatile, all-in-one platform for generative modeling, cross-cell-type generalization, and causal mechanistic investigation of the multiscale regulatory genome.<\/jats:p>","DOI":"10.1093\/nar\/gkag902","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:24:09Z","timestamp":1788780249000},"source":"Crossref","is-referenced-by-count":0,"title":["GenoME: a MoE-based generative model for individualized, multimodal prediction and perturbation of genomic profiles"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3802-5310","authenticated-orcid":false,"given":"Jiachen","family":"Wei","sequence":"first","affiliation":[{"name":"Changping Laboratory , Beijing 102206 ,","place":["China"]},{"name":"School of Science, Westlake University , Hangzhou 310030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xue","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University , Beijing 100871 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chai","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University , Beijing 100871 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4309-9376","authenticated-orcid":false,"given":"Yi Qin","family":"Gao","sequence":"additional","affiliation":[{"name":"Changping Laboratory , Beijing 102206 ,","place":["China"]},{"name":"School of Science, Westlake University , Hangzhou 310030 ,","place":["China"]},{"name":"Beijing National Laboratory for 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