Challenges in measuring and understanding biological noise

Biochemical reactions are intrinsically stochastic, leading to variation in the production of mRNAs and proteins within cells. In the scientific literature, this source of variation is typically referred to as ‘noise’. The observed variability in molecular phenotypes arises from a combination of processes that amplify and attenuate noise. Our ability to quantify cell-to-cell variability in numerous biological contexts has been revolutionized by recent advances in single-cell technology, from imaging approaches through to ‘omics’ strategies. However, defining, accurately measuring and disentangling the stochastic and deterministic components of cell-to-cell variability is challenging. In this Review, we discuss the sources, impact and function of molecular phenotypic variability and highlight future directions to understand its role.Gene expression is subjected to various random processes (referred to as ‘noise’) that contribute to variability in molecular phenotypes. As Eling, Morgan and Marioni describe, there are various challenges to studying this variability, such as disentangling its multilayered sources, distinguishing it from deterministic influences on cellular variability, modelling it with appropriate statistical methods and understanding its practical consequences.