Stochastic dynamics of chemotactic colonies with logistic growth

The interplay between cellular growth and cell-cell signaling is essential for the aggregation and proliferation of bacterial colonies, as well as for the self-organization of cell tissues. To investigate this interplay, we focus here on the collective properties of dividing chemotactic cell colonies by studying their long-time and large-scale dynamics through a renormalization group (RG) approach. The RG analysis reveals that a relevant but unconventional chemotactic interaction -- corresponding to a polarity-induced mechanism -- is generated by fluctuations at macroscopic scales, even when an underlying mechanism is absent at the microscopic level. This emerges from the interplay of the well-known Keller--Segel (KS) chemotactic nonlinearity and cell birth and death processes. At one-loop order, we find no stable fixed point of the RG flow equations. We discuss a connection between the dynamics investigated here and the celebrated Kardar--Parisi--Zhang (KPZ) equation with long-range correlated noise, which points at the existence of a strong-coupling, nonperturbative fixed point.

Optimal Neighborhood Selection for AR-ARCH Random Fields with Application to Mortality

This article proposes an optimal and robust methodology for model selection. The model of interest is a parsimonious alternative framework for modeling the stochastic dynamics of mortality improvement rates introduced recently in the literature. The approach models mortality improvements using a random field specification with a given causal structure instead of the commonly used factor-based decomposition framework. It captures some well-documented stylized facts of mortality behavior including: dependencies among adjacent cohorts, the cohort effects, cross-generation correlations, and the conditional heteroskedasticity of mortality. Such a class of models is a generalization of the now widely used AR-ARCH models for univariate processes. A the framework is general, it was investigated and illustrated a simple variant called the three-level memory model. However, it is not clear which is the best parameterization to use for specific mortality uses. In this paper, we investigate the optimal model choice and parameter selection among potential and candidate models. More formally, we propose a methodology well-suited to such a random field able to select thebest model in the sense that the model is not only correct but also most economical among all thecorrectmodels. Formally, we show that a criterion based on a penalization of the log-likelihood, e.g., the using of the Bayesian Information Criterion, is consistent. Finally, we investigate the methodology based on Monte-Carlo experiments as well as real-world datasets.

A multi-state dynamical process underpins mechano-adaptation in the bacterial flagellar motor

Adaptation is a defining feature of living systems. The bacterial flagellar motor adapts to changes in external mechanical environment by adding or removing torque-generating stator units. However, the molecular mechanism for mechanosensitive motor remodeling remains unclear. Here, we induced stator disassembly using electrorotation, followed by the time-dependent assembly of the individual stator units into the motor. From these experiments, we extracted detailed statistics of the dwell times underlying the stochastic dynamics of stator unit binding and unbinding. The dwell time distribution contains multiple timescales, indicating the existence of multiple stator unit states. Based on these results, we propose a minimal model with four stator unit states – two bound states with different unbinding rates, a diffusive unbound state, and a recently described transiently detached state. Our minimal model quantitatively explains multiple features of the experimental data and allows us to determine the transition rates between all four states. Our experiments and modeling point towards an emergent picture for mechano-adaptive remodeling of the bacterial flagellar motor in which torque generated by bound stator units controls their effective unbinding rate by modulating the transition between the two bound states. Furthermore, the binding rate of stator units with the motor has a non-monotonic dependence on the number of bound units, likely due to two counter-acting effects of motor’s rotation on the binding process.

A hybrid stochastic-deterministic approach to explore multiple infection and evolution in HIV

To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small sub-populations coexist. Here, we describe a hybrid stochastic-deterministic algorithm to simulate mutant evolution in large viral populations, such as acute HIV-1 infection, and further include the multiple infection of cells. We demonstrate that the hybrid method can approximate the fully stochastic dynamics with sufficient accuracy at a fraction of the computational time, and quantify evolutionary end points that cannot be expressed by deterministic models, such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We apply this method to study the role of multiple infection and intracellular interactions among different virus strains (such as complementation and interference) for mutant evolution. Multiple infection is predicted to increase the number of mutants at a given infected cell population size, due to a larger number of infection events. We further find that viral complementation can significantly enhance the spread of disadvantageous mutants, but only in select circumstances: it requires the occurrence of direct cell-to-cell transmission through virological synapses, as well as a substantial fitness disadvantage of the mutant, most likely corresponding to defective virus particles. This, however, likely has strong biological consequences because defective viruses can carry genetic diversity that can be incorporated into functional virus genomes via recombination. Through this mechanism, synaptic transmission in HIV might promote virus evolvability.

The chemical Langevin equation for biochemical systems in dynamic environments

Modelling and simulation of complex biochemical reaction networks form cornerstones of modern biophysics. Many of the approaches developed so far capture temporal fluctuations due to the inherent stochasticity of the biophysical processes, referred to as intrinsic noise. Stochastic fluctuations, however, predominantly stem from the interplay of the network with many other - and mostly unknown - fluctuating processes, as well as with various random signals arising from the extracellular world; these sources contribute extrinsic noise. Here we provide a computational simulation method to probe the stochastic dynamics of biochemical systems subject to both intrinsic and extrinsic noise. We develop an extrinsic chemical Langevin equation - a physically motivated extension of the chemical Langevin equation - to model intrinsically noisy reaction networks embedded in a stochastically fluctuating environment. The extrinsic CLE is a continuous approximation to the Chemical Master Equation (CME) with time-varying propensities. In our approach, noise is incorporated at the level of the CME, and can account for the full dynamics of the exogenous noise process, irrespective of timescales and their mismatches. We show that our method accurately captures the first two moments of the stationary probability density when compared with exact stochastic simulation methods, while reducing the computational runtime by several orders of magnitude. Our approach provides a method that is practical, computationally efficient and physically accurate to study systems that are simultaneously subject to a variety of noise sources.

DeepCME: A deep learning framework for computing solution statistics of the chemical master equation

Stochastic models of biomolecular reaction networks are commonly employed in systems and synthetic biology to study the effects of stochastic fluctuations emanating from reactions involving species with low copy-numbers. For such models, the Kolmogorov’s forward equation is called the chemical master equation (CME), and it is a fundamental system of linear ordinary differential equations (ODEs) that describes the evolution of the probability distribution of the random state-vector representing the copy-numbers of all the reacting species. The size of this system is given by the number of states that are accessible by the chemical system, and for most examples of interest this number is either very large or infinite. Moreover, approximations that reduce the size of the system by retaining only a finite number of important chemical states (e.g. those with non-negligible probability) result in high-dimensional ODE systems, even when the number of reacting species is small. Consequently, accurate numerical solution of the CME is very challenging, despite the linear nature of the underlying ODEs. One often resorts to estimating the solutions via computationally intensive stochastic simulations. The goal of the present paper is to develop a novel deep-learning approach for computing solution statistics of high-dimensional CMEs by reformulating the stochastic dynamics using Kolmogorov’s backward equation. The proposed method leverages superior approximation properties of Deep Neural Networks (DNNs) to reliably estimate expectations under the CME solution for several user-defined functions of the state-vector. This method is algorithmically based on reinforcement learning and it only requires a moderate number of stochastic simulations (in comparison to typical simulation-based approaches) to train the “policy function”. This allows not just the numerical approximation of various expectations for the CME solution but also of its sensitivities with respect to all the reaction network parameters (e.g. rate constants). We provide four examples to illustrate our methodology and provide several directions for future research.

Quantum computing for classical problems: Variational Quantum Eigensolver for activated processes

The theory of stochastic processes impacts both physical and social sciences. At the molecular scale, stochastic dynamics is ubiquitous because of thermal fluctuations. The Fokker-Plank-Smoluchowski equation models the time evolution of the probability density of selected degrees of freedom in the diffusive regime and it is a workhorse of physical chemistry. In this paper, we report the development and implementation of a Variational Quantum Eigensolver procedure to solve the Fokker-Planck-Smoluchowski eigenvalue problem. We show that such an algorithm, typically adopted to address quantum chemistry problems, can be applied effectively to classical systems paving the way to new applications of quantum computers. We compute the conformational transition rate in a linear chain of rotors experiencing nearest-neighbor interaction. We provide a method to encode on the quantum computer the probability distribution for a given conformation of the chain and assess its scalability in terms of operations. Performance analysis on noisy quantum emulators and quantum devices (IBMQ Santiago) is provided for a small chain showing results in good agreement with the classical benchmark without further addition of any error mitigation technique.

Free energy landscape and kinetics of phase transition in two coupled SYK models and the corresponding wormhole-two black hole switching

We propose that the thermodynamics and the kinetics of the phase transition between wormhole and two black hole described by the two coupled SYK model can be investigated in terms of the stochastic dynamics on the underlying free energy landscape. We assume that the phase transition is a stochastic process under the thermal fluctuations. By quantifying the underlying free energy landscape, we study the phase diagram, the kinetic time and its fluctuations in details, which reveal the underlying thermodynamics and kinetics. It is shown that the first order phase transition between wormhole and two black hole described by two coupled SYK model is analogous to the Van der Waals phase transition. Therefore, the emergence of wormhole and two black hole phases, the phase transition and associated kinetics can be quantitatively addressed in our free energy landscape and kinetic framework through the dependence on the barrier height and the temperature.