Fold-change detection in biological systems

TLDR

Fold‑change detection (FCD) is a property of many sensory systems in which dynamics depend only on relative input changes, featuring exact adaptation and the Weber–Fechner law, and is observed in bacterial chemotaxis, mammalian signaling pathways (NF‑κB, Wnt, TGF‑β), and sensory modalities such as vision, hearing, and olfaction. This review surveys circuit motifs that implement FCD—including incoherent type‑1 feedforward loops, nonlinear integral feedback loops, and logarithmic sensors—examines experimental strategies to test and distinguish these mechanisms, and outlines theoretical efforts to map the functional space of FCD circuits while highlighting remaining open questions. The authors detail how incoherent type‑1 feedforward loops, nonlinear integral feedback loops, and logarithmic sensors generate FCD, and describe experimental approaches that can probe and differentiate these mechanisms.

Abstract

Many sensory systems in cells and organisms share a recurring property called fold-change detection (FCD). FCD describes a system whose dynamics – including amplitude and response time – are determined only by the relative change in input signal, rather than its absolute change. FCD entails two important features – exact adaptation and the Weber–Fechner law. Systems with FCD include bacterial and eukaryotic chemotaxis, signaling pathways in mammalian cells such as NF-κB, Wnt and Tgf-β, and organismal vision, hearing and olfaction. Here, we review circuits that can provide FCD such as the incoherent type 1 feedforward loop, the non-linear integral feedback loop, and logarithmic sensor. We review experimental ways to test for FCD and differentiate between FCD mechanisms, and highlight theoretical studies that begin to map the space of FCD circuits and the functions they can provide. Finally, we discuss open questions on the structure and function of FCD systems.