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DynaVelo learns a functional form of the vector field, such that the model can be perturbed in silico and not only used to draw trajectories. We show that DynaVelo recovers the bifurcating in vivo dynamics of wild-type murine germinal center (GC) B cells and reveals how these dynamics change under heterozygous loss of epigenetic regulators\n                    <jats:italic>Arid1a<\/jats:italic>\n                    and\n                    <jats:italic>Ctcf<\/jats:italic>\n                    . In silico perturbation yields dynamic and cell-state-specific gene regulatory networks (GRNs) that recover known TF-to-gene edges in the wild-type GC GRN and predicts those that are disrupted in mutants. Perturbing\n                    <jats:italic>Arid1aHet<\/jats:italic>\n                    GCs in silico identified\n                    <jats:italic>Ctcf<\/jats:italic>\n                    ,\n                    <jats:italic>Stat3<\/jats:italic>\n                    and\n                    <jats:italic>Bcl6<\/jats:italic>\n                    as rescue targets for\n                    <jats:italic>Arid1a<\/jats:italic>\n                    loss. In vivo experiments in double-heterozygous mice confirmed rescue of the\n                    <jats:italic>Arid1aHet<\/jats:italic>\n                    dark-zone phenotype in all three cases, and multiome profiling of\n                    <jats:italic>Arid1aHet<\/jats:italic>\n                    ;\n                    <jats:italic>CtcfHet<\/jats:italic>\n                    GCs validated the predicted shift toward wild-type dynamics.\n                  <\/jats:p>","DOI":"10.1038\/s41587-026-03348-1","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:02:37Z","timestamp":1792573357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep dynamical models of single-cell multiomic velocities predict loss-of-function and rescue perturbations in B cells"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4308-2582","authenticated-orcid":false,"given":"Alireza","family":"Karbalayghareh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Pelzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-3197","authenticated-orcid":false,"given":"Christopher R.","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8074-2287","authenticated-orcid":false,"given":"Ari","family":"Melnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-9138","authenticated-orcid":false,"given":"Darko","family":"Barisic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-5910","authenticated-orcid":false,"given":"Christina S.","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"3348_CR1","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1038\/s41588-024-01745-3","volume":"56","author":"T Zhou","year":"2024","unstructured":"Zhou, T. et al. 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C.S.L. is a scientific advisory board member and holds intellectual property with Episteme Prognostics, unrelated to this study. A.M. has research funding from Janssen, Epizyme and Daiichi Sankyo. A.M. has consulted for Exo Therapeutics, Treeline Biosciences, AstraZeneca and Epizyme.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}