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Recent developments in synthetic biology, next-generation sequencing, and machine learning provide an unprecedented opportunity to rationally design new disease treatments based on measured responses to gene perturbations and drugs to reprogram cells. The main challenges to seizing this opportunity are the incomplete knowledge of the cellular network and the combinatorial explosion of possible interventions, both of which are insurmountable by experiments. To address these challenges, we develop a transfer learning approach to control cell behavior that is pre-trained on transcriptomic data associated with human cell fates, thereby generating a model of the network dynamics that can be transferred to specific reprogramming goals. The approach combines transcriptional responses to gene perturbations to minimize the difference between a given pair of initial and target transcriptional states. We demonstrate our approach’s versatility by applying it to a microarray dataset comprising >9,000 microarrays across 54 cell types and 227 unique perturbations, and an RNASeq dataset consisting of >10,000 sequencing runs across 36 cell types and 138 perturbations. Our approach reproduces known reprogramming protocols with an AUROC of 0.91 while innovating over existing methods by pre-training an adaptable model that can be tailored to specific reprogramming transitions. We show that the number of gene perturbations required to steer from one fate to another increases with decreasing developmental relatedness and that fewer genes are needed to progress along developmental paths than to regress. These findings establish a proof-of-concept for our approach to computationally design control strategies and provide insights into how gene regulatory networks govern phenotype. 

External flows of energy, entropy, and matter can cause sudden transitions in the stability of biological and industrial systems, fundamentally altering their dynamical function. How might we control and design these transitions in chemical reaction networks? Here, we analyze transitions giving rise to complex behavior in random reaction networks subject to external driving forces. In the absence of driving, we characterize the uniqueness of the steady state and identify the percolation of a giant connected component in these networks as the number of reactions increases. When subject to chemical driving (influx and outflux of chemical species), the steady state can undergo bifurcations, leading to multistability or oscillatory dynamics. By quantifying the prevalence of these bifurcations, we show how chemical driving and network sparsity tend to promote the emergence of these complex dynamics and increased rates of entropy production. We show that catalysis also plays an important role in the emergence of complexity, strongly correlating with the prevalence of bifurcations. Our results suggest that coupling a minimal number of chemical signatures with external driving can lead to features present in biochemical processes and abiogenesis. 

Abstract The 2021 Nobel Prize in Physics recognized the fundamental role of complex systems in the natural sciences. In order to celebrate this milestone, this editorial presents the point of view of the editorial board of JPhys Complexity on the achievements, challenges, and future prospects of the field. To distinguish the voice and the opinion of each editor, this editorial consists of a series of editor perspectives and reflections on few selected themes. A comprehensive and multi-faceted view of the field of complexity science emerges. We hope and trust that this open discussion will be of inspiration for future research on complex systems. 

A widely held assumption on network dynamics is that similar components are more likely to exhibit similar behavior than dissimilar ones and that generic differences among them are necessarily detrimental to synchronization. Here, we show that this assumption does not generally hold in oscillator networks when communication delays are present. We demonstrate, in particular, that random parameter heterogeneity among oscillators can consistently rescue the system from losing synchrony. This finding is supported by electrochemical-oscillator experiments performed on a multielectrode array network. Remarkably, at intermediate levels of heterogeneity, random mismatches are more effective in promoting synchronization than parameter assignments specifically designed to facilitate identical synchronization. Our results suggest that, rather than being eliminated or ignored, intrinsic disorder in technological and biological systems can be harnessed to help maintain coherence required for function.