Inference of plasmid copy number mean and noise from single cell gene expression data

TL;DR

This paper develops a comprehensive model to infer plasmid copy number mean and noise from single-cell gene expression data, accounting for various biological sources of fluorescence variability.

Contribution

It introduces a detailed calculation linking fluorescence fluctuations to plasmid noise, improving accuracy over previous simplified models.

Findings

Accurate estimation of plasmid copy number noise from fluorescence data.

Inclusion of bacterial growth, division, and partitioning effects in the model.

Use of chromosome as a reference for self-consistent noise extraction.

Abstract

Plasmids are extra-chromosomal DNA molecules which code for their own replication. We previously reported a setup using genes coding for fluorescent proteins of two colors that allowed us, using a simple model, to extract the plasmid copy number noise in a monoclonal population of bacteria [J. Wong Ng et al., Phys. Rev. E, 81, 011909 (2010)]. Here we present a detailed calculation relating this noise to the measured levels of fluorescence, taking into account all sources of fluorescence fluctuations: the fluctuation of gene expression as in the simple model, but also the growth and division of bacteria, the non-uniform distribution of their ages, the random partition of proteins at divisions and the replication and partition of plasmids and chromosome. We show how using the chromosome as a reference helps extracting the plasmid copy number noise in a self-consistent manner.