Adaptive information processing of network modules to dynamic and spatial stimuli

Abstract

BackgroundAdaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts. Much of the current understanding of adaptation in network modules/motifs is based on their response to simple stimuli. Recently, there have also been studies of adaptation in dynamic stimuli. However a broader synthesis of how different circuits of adaptation function, and which circuits enable a broader adaptive behaviour in classes of more complex and spatial stimuli is largely missing.ResultsWe study the response of a variety of adaptive circuits to time-varying stimuli such as ramps, periodic stimuli and static and dynamic spatial stimuli. We find that a variety of responses can be seen in ramp stimuli, making this a basis for discriminating between even similar circuits. We also find that a number of circuits adapt exactly to ramp stimuli, and dissect these circuits to pinpoint what characteristics (architecture, feedback, biochemical aspects, information processing ingredients) allow for this. These circuits include incoherent feedforward motifs, inflow-outflow motifs and transcritical circuits. We find that changes in location in such circuits where a signal acts can result in non-adaptive behaviour in ramps, even though the location was associated with exact adaptation in step stimuli. We also demonstrate that certain augmentations of basic inflow-outflow motifs can alter the behaviour of the circuit from exact adaptation to non-adaptive behaviour. When subject to periodic stimuli, some circuits (inflow-outflow motifs and transcritical circuits) are able to maintain an average output independent of the characteristics of the input. We build on this to examine the response of adaptive circuits to static and dynamic spatial stimuli. We demonstrate how certain circuits can exhibit a graded response in spatial static stimuli with an exact maintenance of the spatial mean-value. Distinct features which emerge from the consideration of dynamic spatial stimuli are also discussed. Finally, we also build on these results to show how different circuits which show any combination of presence or absence of exact adaptation in ramps, exact mainenance of time average output in periodic stimuli and exact maintenance of spatial average of output in static spatial stimuli may be realized.ConclusionsBy studying a range of network circuits/motifs on one hand and a range of stimuli on the other, we isolate characteristics of these circuits (structural) which enable different degrees of exact adaptive and homeostatic behaviour in such stimuli, how they may be combined, and also identify cases associated with non-homeostatic behaviour. We also reveal constraints associated with locations where signals may act to enable homeostatic behaviour and constraints associated with augmentations of circuits. This consideration of multiple experimentally/naturally relevant stimuli along with circuits of adaptation of relevance in natural and engineered biology, provides a platform for deepening our understandin...

Frequency switching between oscillatory homeostats and the regulation of p53

“…To achieve robustness of feedback controllers by integral control it became clear that certain reaction kinetic conditions need to be met. These conditions include zero-order kinetics [9,10,[14][15][16][17][18][19], autocatalysis [20][21][22], and secondorder (bimolecular/antithetic) reactions [23,24], which were implemented into various controller motifs, synthetic gene networks, and other negative feedback structures [18,[25][26][27].…”

Symmetry breaking meets multisite modification

“…(iv) There are different ways in which ACR may be obtained (for instance, in bifunctional enzymes Batchelor and Goulian, 2003 ; Krishnan et al, 2020 ). The mechanism seen here shares a feature of ACR observed in autocatalytic networks, arising from a transcritical bifurcation ( Shinar and Feinberg, 2011 ; Krishnan and Floros, 2019 ) as being intimately tied to a nonlinear dynamic transition arising from the biochemistry. In both cases, there is more than one steady state possible, and one of the steady states exhibits the ACR.…”

An amplified derepression controller with multisite inhibition and positive feedback

“…It became evident that certain kinetic conditions within a negative feedback loop, such as zero-order kinetics [18][19][20][22][23][24], autocatalysis [25][26][27], or second-order (bimolecular/antithetic) kinetics [28,29] can lead to robust adaptation [30,31] by integral control where an intrinsic integration of the error between set-point and the actual value of the controlled variable is automatically performed. When these feedback motifs were investigated towards timedependent perturbations, it turned out that controller performances can differ significantly, either due to the structure of the feedback loop or due to the kinetics of how the integral controller is implemented [32,33].…”