Reconstructing dynamic molecular states from single-cell time series

J R Soc Interface. 2016 Sep;13(122):20160533. doi: 10.1098/rsif.2016.0533.

Abstract

The notion of state for a system is prevalent in the quantitative sciences and refers to the minimal system summary sufficient to describe the time evolution of the system in a self-consistent manner. This is a prerequisite for a principled understanding of the inner workings of a system. Owing to the complexity of intracellular processes, experimental techniques that can retrieve a sufficient summary are beyond our reach. For the case of stochastic biomolecular reaction networks, we show how to convert the partial state information accessible by experimental techniques into a full system state using mathematical analysis together with a computational model. This is intimately related to the notion of conditional Markov processes and we introduce the posterior master equation and derive novel approximations to the corresponding infinite-dimensional posterior moment dynamics. We exemplify this state reconstruction approach using both in silico data and single-cell data from two gene expression systems in Saccharomyces cerevisiae, where we reconstruct the dynamic promoter and mRNA states from noisy protein abundance measurements.

Keywords: chemical master equation; continuous time Markov chains; gene expression; moment dynamics; optimal filtering.

MeSH terms

  • Gene Expression Regulation, Fungal / physiology*
  • Markov Chains
  • Models, Biological*
  • Promoter Regions, Genetic / physiology*
  • RNA, Fungal / biosynthesis*
  • RNA, Messenger / biosynthesis*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*

Substances

  • RNA, Fungal
  • RNA, Messenger