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Assessing Markovian and Delay Models for Single-Nucleus RNA Sequencing.

Gennady Gorin1, Shawn Yoshida1,2, Lior Pachter3,4

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|October 12, 2023
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Summary

This study models RNA dynamics with delays, finding that nuclear export kinetics are consistent with standard waiting times. Our findings simplify models of gene expression and RNA processing.

Keywords:
Chemical master equationsDelay processesMarkov chain Monte CarloModel identificationSingle-cell RNA sequencingStochastic simulation

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Area of Science:

  • Molecular Biology
  • Systems Biology
  • Computational Biology

Background:

  • The RNA life-cycle involves sequential reactions, necessitating models that account for temporal delays in transcriptional dynamics.
  • Existing models often simplify reaction kinetics, potentially overlooking the impact of delays on RNA production and processing.

Purpose of the Study:

  • To develop and analyze computational models of transcriptional dynamics incorporating general sets of delayed monomolecular reactions.
  • To investigate the influence of delays on RNA copy number distributions in systems with splicing, degradation, and catalysis.
  • To analyze single-cell and single-nucleus RNA sequencing data to infer the nature of waiting times in nuclear export.

Main Methods:

  • Development of numerical strategies for calculating RNA copy number distributions from delayed reaction models.
  • Application of these models to simulate systems involving RNA splicing, degradation, and catalytic reactions.
  • Analysis of experimental single-cell and single-nucleus RNA sequencing data using the developed computational framework.

Main Results:

  • Successfully calculated RNA copy number distributions for various delayed transcriptional models.
  • Demonstrated the utility of the models in analyzing complex RNA processing pathways.
  • Analysis of RNA sequencing data indicated that nuclear export kinetics can be described by Markovian waiting times, without needing non-Markovian models.

Conclusions:

  • Models incorporating delays are crucial for accurately representing RNA life-cycle dynamics.
  • The developed numerical strategies provide a robust method for analyzing such models.
  • Experimental data suggest that nuclear export kinetics are simpler than previously assumed, adhering to standard waiting time distributions.