150550 20251017144647.0 doi 10.1103/PhysRevResearch.7.013010 sideral 142627 ART-2025-142627 eng Le Treut, Guillaume Markov-bridge generation of transition paths and its application to cell-fate choice 2025 Access copy available to the general public Unrestricted We present a method to sample Markov-chain trajectories constrained to both the initial and final conditions, which we term Markov bridges. The trajectories are conditioned to end in a specific state at a given time. We derive the master equation for Markov bridges, which exhibits the original transition rates scaled by a time-dependent factor. Trajectories can then be generated using a refined version of the Gillespie algorithm. We illustrate the benefits of our method by sampling trajectories in the Müller-Brown potential. This allows us to generate transition paths which would otherwise be obtained at a high computational cost with standard kinetic Monte Carlo methods because commitment to a transition path is essentially a rare event. We then apply our method to a single-cell RNA sequencing dataset from mouse pancreatic cells to investigate the cell differentiation pathways of endocrine-cell precursors. By sampling Markov bridges for a specific differentiation pathway, we obtain a time-resolved dynamics that can reveal features such as cell types which behave as bottlenecks. The ensemble of trajectories also gives information about the fluctuations around the most likely path. For example, we quantify the statistical weights of different branches in the differentiation pathway to alpha cells. info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136374NB-C21 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ancheta, Sarah Huber, Greg Orland, Henri Yllanes, David (orcid)0000-0001-7276-2942 7, 1 (2025), 013010 [12 pp.] Phys. rev. res. Physical Review Research 2643-1564 2844255 http://zaguan.unizar.es/record/150550/files/texto_completo.pdf Versión publicada 3075061 http://zaguan.unizar.es/record/150550/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:150550 articulos driver 2025-10-17-14:34:35 ARTICLE