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While the Waddington landscape offers a valuable conceptual framework for understanding cellular dynamics, its quantitative reconstruction remains a significant challenge in systems biology and biophysics. Recent methodological advances in single-cell omics technologies, computational modeling approaches, and nonlinear dynamical systems theory have facilitated progress toward quantitative reconstruction of the Waddington landscape, thereby transforming this heuristic metaphor into a predictive theoretical framework. In this review, we summarize the theoretical foundations of the Waddington landscape, categorize current computational and mathematical approaches for the Waddington landscape reconstruction. Meanwhile, we highlight the potential applications and inherent limitations of these approaches in characterizing cellular behaviors, predicting cell fate decisions, and modulating developmental trajectories.<\/jats:p>","DOI":"10.1093\/bib\/bbaf661","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T13:01:13Z","timestamp":1764075673000},"source":"Crossref","is-referenced-by-count":1,"title":["Beyond metaphor: quantitative reconstruction of Waddington landscape and exploration of cellular behavior"],"prefix":"10.1093","volume":"26","author":[{"given":"Yourui","family":"Han","sequence":"first","affiliation":[{"name":"School of Computer Science , Northwestern Polytechnical University, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 710072,","place":["China"]}]},{"given":"Bolin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Computer Science , Northwestern Polytechnical University, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 710072,","place":["China"]},{"name":"Key Laboratory of Big Data Storage and Management , Northwestern Polytechnical University, Ministry of Industry and Information Technology, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 710072,","place":["China"]}]},{"given":"Jinlei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Computer Science , Northwestern Polytechnical University, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 710072,","place":["China"]}]},{"given":"Xuequn","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Computer Science , Northwestern Polytechnical University, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 710072,","place":["China"]},{"name":"Key Laboratory of Big Data Storage and Management , Northwestern Polytechnical University, Ministry of Industry and Information Technology, 1 Dongxiang Road, Chang\u2019an District, Xi\u2019an 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