A stochastic vs deterministic perspective on the timing of cellular events.

Cells are the fundamental units of life, and like all life forms, they change over time. Changes in cell state are driven by molecular processes; of these many are initiated when molecule numbers reach and exceed specific thresholds, a characteristic that can be described as "digital cellular logic". Here we show how molecular and cellular noise profoundly influence the time to cross a critical threshold-the first-passage time-and map out scenarios in which stochastic dynamics result in shorter or longer average first-passage times compared to noise-less dynamics.

The chemical Langevin equation for biochemical systems in dynamic environments.

Modeling and simulation of complex biochemical reaction networks form cornerstones of modern biophysics. Many of the approaches developed so far capture temporal fluctuations due to the inherent stochasticity of the biophysical processes, referred to as intrinsic noise. Stochastic fluctuations, however, predominantly stem from the interplay of the network with many other-and mostly unknown-fluctuating processes, as well as with various random signals arising from the extracellular world; these sources contribute extrinsic noise.

Pathway dynamics can delineate the sources of transcriptional noise in gene expression.

Single-cell expression profiling opens up new vistas on cellular processes. Extensive cell-to-cell variability at the transcriptomic and proteomic level has been one of the stand-out observations. Because most experimental analyses are destructive we only have access to snapshot data of cellular states.

Noise distorts the epigenetic landscape and shapes cell-fate decisions.

The Waddington epigenetic landscape has become an iconic representation of the cellular differentiation process. Recent single-cell transcriptomic data provide new opportunities for quantifying this originally conceptual tool, offering insight into the gene regulatory networks underlying cellular development. While many methods for constructing the landscape have been proposed, by far the most commonly employed approach is based on computing the landscape as the negative logarithm of the steady-state probability distribution.

Exactly solvable models of stochastic gene expression.

Stochastic models are key to understanding the intricate dynamics of gene expression. However, the simplest models that only account for active and inactive states of a gene fail to capture common observations in both prokaryotic and eukaryotic organisms. Here, we consider multistate models of gene expression that generalize the canonical Telegraph process and are capable of capturing the joint effects of transcription factors, heterochromatin state, and DNA accessibility (or, in prokaryotes, sigma-factor activity) on transcript abundance.

Extrinsic Noise and Heavy-Tailed Laws in Gene Expression.

Noise in gene expression is one of the hallmarks of life at the molecular scale. Here we derive analytical solutions to a set of models describing the molecular mechanisms underlying transcription of DNA into RNA. Our ansatz allows us to incorporate the effects of extrinsic noise-encompassing factors external to the transcription of the individual gene-and discuss the ramifications for heterogeneity in gene product abundance that has been widely observed in single cell data.