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Previous approaches utilizing the deterministic dynamics and steady-state assumption on gene expression states are insufficient to achieve favorable results for the data involving transient process. We present a dynamical approach, Storm (Stochastic models of RNA metabolic-labeling), to overcome these limitations by solving stochastic differential equations of gene expression dynamics. The derivation reveals that the new mRNA sequencing data obeys different types of cell-specific Poisson distributions when jointly considering both biological and cell-specific technical noise. Storm deals with measured counts data directly and extends the RNA velocity methodology based on metabolic labeling scRNA-seq data to transient stochastic systems. Furthermore, we relax the constant parameter assumption over genes\/cells to obtain gene-cell-specific transcription\/splicing rates and gene-specific degradation rates, thus revealing time-dependent and cell-state-specific transcriptional regulations. 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regression analysis","volume":"54","author":"S Menard","year":"2000","journal-title":"The American Statistician"},{"issue":"1","key":"pcbi.1012606.ref030","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1038\/s41467-019-10500-w","article-title":"Simulating multiple faceted variability in single cell RNA sequencing","volume":"10","author":"X Zhang","year":"2019","journal-title":"Nature communications"},{"key":"pcbi.1012606.ref031","first-page":"2021","article-title":"VeloSim: Simulating single cell gene-expression and RNA velocity","author":"Z Zhang","year":"2021","journal-title":"BioRxiv"},{"issue":"2","key":"pcbi.1012606.ref032","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.cell.2014.05.038","article-title":"Mechanism of transcriptional bursting in bacteria","volume":"158","author":"S Chong","year":"2014","journal-title":"Cell"},{"issue":"13","key":"pcbi.1012606.ref033","doi-asserted-by":"crossref","first-page":"i218","DOI":"10.1093\/bioinformatics\/bty256","article-title":"Dissecting newly transcribed and old RNA using GRAND-SLAM","volume":"34","author":"C J\u00fcrges","year":"2018","journal-title":"Bioinformatics"},{"issue":"6","key":"pcbi.1012606.ref034","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nmeth.2930","article-title":"Validation of noise models for single-cell transcriptomics","volume":"11","author":"D Gr\u00fcn","year":"2014","journal-title":"Nature methods"},{"issue":"302","key":"pcbi.1012606.ref035","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/14786440009463897","article-title":"X. On the criterion that a given system of deviations from the probable in the case of a correlated system of variables is such that it can be reasonably supposed to have arisen from random sampling","volume":"50","author":"K Pearson","year":"1900","journal-title":"The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science"},{"key":"pcbi.1012606.ref036","doi-asserted-by":"crossref","unstructured":"Benhamou E, Melot V. Seven proofs of the Pearson Chi-squared independence test and its graphical interpretation. arXiv preprint arXiv:180809171. 2018;.","DOI":"10.2139\/ssrn.3239829"},{"issue":"3","key":"pcbi.1012606.ref037","doi-asserted-by":"crossref","first-page":"e8604","DOI":"10.15252\/msb.20188604","article-title":"Evidence that the human cell cycle is a series of uncoupled, memoryless phases","volume":"15","author":"HX Chao","year":"2019","journal-title":"Molecular systems biology"},{"issue":"4","key":"pcbi.1012606.ref038","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1137\/1118101","article-title":"Calculation of the Wasserstein distance between probability distributions on the line","volume":"18","author":"S Vallender","year":"1974","journal-title":"Theory of Probability & Its Applications"},{"key":"pcbi.1012606.ref039","first-page":"279","article-title":"A review on modern computational optimal transport methods with applications in biomedical research","author":"J Zhang","year":"2021","journal-title":"Modern Statistical Methods for Health Research"},{"issue":"2","key":"pcbi.1012606.ref040","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41587-021-01031-1","article-title":"Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin","volume":"40","author":"M Tedesco","year":"2022","journal-title":"Nature Biotechnology"},{"issue":"8","key":"pcbi.1012606.ref041","doi-asserted-by":"crossref","first-page":"e1011288","DOI":"10.1371\/journal.pcbi.1011288","article-title":"The specious art of single-cell genomics","volume":"19","author":"T Chari","year":"2023","journal-title":"PLoS Computational Biology"},{"issue":"9","key":"pcbi.1012606.ref042","doi-asserted-by":"crossref","first-page":"e1010031","DOI":"10.1371\/journal.pcbi.1010031","article-title":"Towards reliable quantification of cell state velocities","volume":"18","author":"V Marot-Lassauzaie","year":"2022","journal-title":"PLoS Computational Biology"},{"issue":"1","key":"pcbi.1012606.ref043","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13059-023-03065-x","article-title":"Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates","volume":"24","author":"SC Zheng","year":"2023","journal-title":"Genome biology"},{"key":"pcbi.1012606.ref044","first-page":"2023","article-title":"Graph-Dynamo: Learning stochastic cellular state transition dynamics from single cell data","author":"Y Zhang","year":"2023","journal-title":"BioRxiv"},{"key":"pcbi.1012606.ref045","first-page":"1","article-title":"PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells","volume":"20","author":"FA Wolf","year":"2019","journal-title":"Genome biology"},{"issue":"1","key":"pcbi.1012606.ref046","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1038\/s41467-022-30545-8","article-title":"Cell cycle gene regulation dynamics revealed by RNA velocity and deep-learning","volume":"13","author":"A Riba","year":"2022","journal-title":"Nature communications"},{"key":"pcbi.1012606.ref047","first-page":"2024","article-title":"Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations","author":"AR Lederer","year":"2024","journal-title":"BioRxiv"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012606","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012606","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T14:07:40Z","timestamp":1733148460000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012606"}},"subtitle":[],"editor":[{"given":"Laleh","family":"Haghverdi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012606","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.21.545990","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]}}}