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Published March 15, 2022 | Supplemental Material + Accepted Version + Submitted
Journal Article Open

Modeling bursty transcription and splicing with the chemical master equation

Abstract

Splicing cascades that alter gene products posttranscriptionally also affect expression dynamics. We study a class of processes and associated distributions that emerge from models of bursty promoters coupled to directed acyclic graphs of splicing. These solutions provide full time-dependent joint distributions for an arbitrary number of species with general noise behaviors and transient phenomena, offering qualitative and quantitative insights about how splicing can regulate expression dynamics. Finally, we derive a set of quantitative constraints on the minimum complexity necessary to reproduce gene coexpression patterns using synchronized burst models. We validate these findings by analyzing long-read sequencing data, where we find evidence of expression patterns largely consistent with these constraints.

Additional Information

© 2022 Biophysical Society. Received 30 July 2021, Accepted 3 February 2022, Available online 7 February 2022. The spectral solution was derived by Meichen Fang. G.G. and L.P. were partially funded by NIH U19MH114830. The DNA illustration used in Figs. S1, S2, and S4, modified from (70), is a derivative of the DNA Twemoji by Twitter, Inc., used under CC-BY 4.0. The directed acyclic graph generation code was adapted from the IPython Parallel reference documentation: https://ipyparallel.readthedocs.io/en/latest/dag_dependencies.html. Author contributions. L.P. and G.G. designed the research and wrote the article. G.G. derived and implemented the analytical solutions, validated them against simulations, and performed the sequencing data analysis. Code availability. Google Colab Python notebooks that reproduce the analyses and benchmarking are available at https://github.com/pachterlab/GP_2021_2.

Attached Files

Accepted Version - 1-s2.0-S0006349522001047-main_acc.pdf

Submitted - 2021.03.24.436847v2.full.pdf

Supplemental Material - 1-s2.0-S0006349522001047-mmc1.pdf

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Additional details

Created:
August 20, 2023
Modified:
December 22, 2023