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• W3125096507 abstract "The discrete chemical master equation (dCME) provides a fundamental framework for studying stochasticity in mesoscopic networks. Because of the multi-scale nature of many networks where reaction rates have large disparity, directly solving dCMEs is intractable due to the exploding size of the state space. It is important to truncate the state space effectively with quantified errors, so accurate solutions can be computed. It is also important to know if all major probabilistic peaks have been computed. Here we introduce the Accurate CME (ACME) algorithm for obtaining direct solutions to dCMEs. With multi-finite buffers for reducing the state space by O(n!), exact steady-state and time-evolving network probability landscapes can be computed. We further describe a theoretical framework of aggregating microstates into a smaller number of macrostates by decomposing a network into independent aggregated birth and death processes, and give an a priori method for rapidly determining steady-state truncation errors. The maximal sizes of the finite buffers for a given error tolerance can also be pre-computed without costly trial solutions of dCMEs. We show exactly computed probability landscapes of three multi-scale networks, namely, a 6-node toggle switch, 11-node phage-lambda epigenetic circuit, and 16-node MAPK cascade network, the latter two with no known solutions. We also show how probabilities of rare events can be computed from first-passage times, another class of unsolved problems challenging for simulation-based techniques due to large separations in time scales. Overall, the ACME method enables accurate and efficient solutions of the dCME for a large class of networks." @default.
• W3125096507 created "2021-02-01" @default.
• W3125096507 creator A5058408763 @default.
• W3125096507 creator A5078913227 @default.
• W3125096507 creator A5091558783 @default.
• W3125096507 date "2016-01-01" @default.
• W3125096507 modified "2023-09-25" @default.
• W3125096507 title "Accurate Chemical Master Equation Solution Using Multi-Finite Buffers" @default.
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• W3125096507 doi "https://doi.org/10.1137/15m1034180" @default.
• W3125096507 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27761104" @default.
• W3125096507 hasPublicationYear "2016" @default.
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