Statistical inference for a quasi birth-death model of RNA transcription

BMC Bioinformatics. 2022 Mar 26;23(1):105. doi: 10.1186/s12859-022-04638-6.

Abstract

Background: A birth-death process of which the births follow a hypoexponential distribution with L phases and are controlled by an on/off mechanism, is a population process which we call the on/off-seq-L process. It is a suitable model for the dynamics of a population of RNA molecules in a single living cell. Motivated by this biological application, our aim is to develop a statistical method to estimate the model parameters of the on/off-seq-L process, based on observations of the population size at discrete time points, and to apply this method to real RNA data.

Methods: It is shown that the on/off-seq-L process can be seen as a quasi birth-death process, and an Erlangization technique can be used to approximate the corresponding likelihood function. An extensive simulation-based numerical study is carried out to investigate the performance of the resulting estimation method.

Results and conclusion: A statistical method is presented to find maximum likelihood estimates of the model parameters for the on/off-seq-L process. Numerical complications related to the likelihood maximization are identified and analyzed, and solutions are presented. The proposed estimation method is a highly accurate method to find the parameter estimates. Based on real RNA data, the on/off-seq-3 process emerges as the best model to describe RNA transcription.

Keywords: Erlangization technique; Maximum likelihood estimation; Quasi birth–death process; RNA transcription.

MeSH terms

  • Computer Simulation
  • Likelihood Functions
  • RNA* / genetics
  • Sequence Analysis, RNA / methods

Substances

  • RNA