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Traditional research studies, experiments, and biochemical analyses, give rise to important insights, although they are restricted in spatiotemporal resolution and processing power, thereby precluding the understanding of dynamic cross-scale biological events . Breakthroughs in artificial intelligence (AI) have given birth to the AI virtual cell (AIVC) as a new way to do research. By integrating multi-omics data and mixing methods from multidisciplinary models, AIVC establishes a digital twin system to simulate cell functions and behaviors. AIVC still faces a number of pressing challenges that need to be addressed in its current development stage. In this review, we are proposing a unified definition and technical framework for AIVC and analyze in detail the cross-scale coupling mechanisms of the \u201cgene\u2013protein\u2013pathway\u2013cell\u201d hierarchy. Furthermore, we decompose the technical construction framework of AIVC from cross-scale representation engineering, functional submodule design, and multi-component dynamic regulation mechanisms. Additionally, we summarize the existing models and datasets in the field to provide reference resources for researchers. Finally, we deeply discuss the challenges faced by AIVC, such as data heterogeneity and model interpretability, and aim to accelerate the research progress in the AIVC field while driving the life sciences to shift from observational analysis to a paradigm that integrates predictability and innovation. Despite being in the early stage, AIVC is a trending topic that has garnered widespread interest. This review aims to integrate existing models, datasets, and technical ideas to provide a unified framework for field development.<\/jats:p>","DOI":"10.1093\/bib\/bbag104","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:19:05Z","timestamp":1771244345000},"source":"Crossref","is-referenced-by-count":0,"title":["Artificial intelligence-enabled multi-scale virtual cell: perspective, challenges, and opportunities"],"prefix":"10.1093","volume":"27","author":[{"given":"Huasen","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 ,","place":["China"]}]},{"given":"Xiaoyu","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 ,","place":["China"]}]},{"given":"Xiangpeng","family":"Bi","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-1029","authenticated-orcid":false,"given":"Wenjian","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 ,","place":["China"]}]},{"given":"Haibo","family":"Ni","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University , 22 Hankou Road, Gulou District, Nanjing 210008 ,","place":["China"]}]},{"given":"Zhiqiang","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 ,","place":["China"]},{"name":"College of Computer Science and Technology, Qingdao University , 308 Ningxia Road, Shinan District, Qingdao 266071 ,","place":["China"]}]},{"given":"Pin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Echocardiography, The Affiliated Hospital of Qingdao University , 16 Jiangsu Road, Shinan District, Qingdao 266000 ,","place":["China"]}]},{"given":"Henggui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Physics and Astronomy, University of Manchester , Oxford Road, Manchester M13 9PL ,","place":["United Kingdom"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-9709","authenticated-orcid":false,"given":"Shugang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology, Ocean University of China , 238 Songling Road, Laoshan District, Qingdao 266404 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