Gene regulatory networks' dynamics are modified by transient stimuli GRNs have several different types of memory, including associative conditioning Evolution favored GRN memory, and differentiated cells have the most memory capacity Training GRNs offers a novel biomedical strategy not dependent on genetic rewiring

Brains exhibit plasticity, multi-scale integration of information, computation and memory, having evolved by specialization of non-neural cells that already possessed many of the same molecular components and functions. The emerging field of basal cognition provides many examples of decision-making throughout a wide range of non-neural systems. How can biological information processing across scales of size and complexity be quantitatively characterized and exploited in biomedical settings? We use pattern regulation as a context in which to introduce the Cognitive Lens—a strategy using well-established concepts from cognitive and computer science to complement mechanistic investigation in biology. To facilitate the assimilation and application of these approaches across biology, we review tools from various quantitative disciplines, including dynamical systems, information theory and least-action principles. We propose that these tools can be extended beyond neural settings to predict and control systems-level outcomes, and to understand biological patterning as a form of primitive cognition. We hypothesize that a cognitive-level information-processing view of the functions of living systems can complement reductive perspectives, improving efficient top-down control of organism-level outcomes. Exploration of the deep parallels across diverse quantitative paradigms will drive integrative advances in evolutionary biology, regenerative medicine, synthetic bioengineering, cognitive neuroscience and artificial intelligence. This article is part of the theme issue ‘Liquid brains, solid brains: How distributed cognitive architectures process information’.

Biological organisms learn from interactions with their environment throughout their lifetime. For artificial systems to successfully act and adapt in the real world, it is desirable to similarly be able to learn on a continual basis. This challenge is known as lifelong learning, and remains to a large extent unsolved. In this perspective article, we identify a set of key capabilities that artificial systems will need to achieve lifelong learning. We describe a number of biological mechanisms, both neuronal and non-neuronal, that help explain how organisms solve these challenges, and present examples of biologically inspired models and biologically plausible mechanisms that have been applied to artificial intelligence systems in the quest towards development of lifelong learning machines. We discuss opportunities to further our understanding and advance the state of the art in lifelong learning, aiming to bridge the gap between natural and artificial intelligence.

Living systems comprise interacting biochemical components in very large networks. Given their high connectivity, biochemical dynamics are surprisingly not chaotic but quite robust to perturbations—a feature C.H. Waddington named canalization. Because organisms are also flexible enough to evolve, they arguably operate in a critical dynamical regime between order and chaos. The established theory of criticality is based on networks of interacting automata where Boolean truth values model presence/absence of biochemical molecules. The dynamical regime is predicted using network connectivity and node bias (to be on/off) as tuning parameters. Revising this to account for canalization leads to a significant improvement in dynamical regime prediction. The revision is based on effective connectivity , a measure of dynamical redundancy that buffers automata response to some inputs. In both random and experimentally validated systems biology networks, reducing effective connectivity makes living systems operate in stable or critical regimes even though the structure of their biochemical interaction networks predicts them to be chaotic. This suggests that dynamical redundancy may be naturally selected to maintain living systems near critical dynamics, providing both robustness and evolvability. By identifying how dynamics propagates preferably via effective pathways, our approach helps to identify precise ways to design and control network models of biochemical regulation and signalling.

The extent to which the components of a biological system are (non)linearly regulated determines how amenable they are to therapy and control. To better understand this property termed “regulatory nonlinearity”, we analyzed a suite of 137 published Boolean network models, containing a variety of complex nonlinear regulatory interactions, using a probabilistic generalization of Boolean logic that George Boole himself had proposed. Leveraging the continuous-nature of this formulation, we used Taylor decomposition to approximate the models with various levels of regulatory nonlinearity. A comparison of the resulting series of approximations of the biological models with appropriate random ensembles revealed that biological regulation tends to be less nonlinear than expected, meaning that higher-order interactions among the regulatory inputs tend to be less pronounced. A further categorical analysis of the biological models revealed that the regulatory nonlinearity of cancer and disease networks could not only be sometimes higher than expected but also be relatively more variable. We show that this variation is caused by differences in the apportioning of information among the various orders of regulatory nonlinearity. Our results suggest that there may have been a weak but discernible selection pressure for biological systems to evolve linear regulation on average, but for certain systems such as cancer, on the other hand, to simultaneously evolve more nonlinear rules.