Fast reactions with non-interacting species in stochastic reaction networks

<abstract><p>We consider stochastic reaction networks modeled by continuous-time Markov chains. Such reaction networks often contain many reactions, potentially occurring at different time scales, and have unknown parameters (kinetic rates, total amounts). This makes their analysis complex. We examine stochastic reaction networks with non-interacting species that often appear in examples of interest (e.g. in the two-substrate Michaelis Menten mechanism). Non-interacting species typically appear as intermediate (or transient) chemical complexes that are depleted at a fast rate. We embed the Markov process of the reaction network into a one-parameter family under a two time-scale approach, such that molecules of non-interacting species are degraded fast. We derive simplified reaction networks where the non-interacting species are eliminated and that approximate the scaled Markov process in the limit as the parameter becomes small. Then, we derive sufficient conditions for such reductions based on the reaction network structure for both homogeneous and time-varying stochastic settings, and study examples and properties of the reduction.</p></abstract>

Stationary distributions via decomposition of stochastic reaction networks

We examine reaction networks (CRNs) through their associated continuous-time Markov processes. Studying the dynamics of such networks is in general hard, both analytically and by simulation. In particular, stationary distributions of stochastic reaction networks are only known in some cases. We analyze class properties of the underlying continuous-time Markov chain of CRNs under the operation of join and examine conditions such that the form of the stationary distributions of a CRN is derived from the parts of the decomposed CRNs. The conditions can be easily checked in examples and allow recursive application. The theory developed enables sequential decomposition of the Markov processes and calculations of stationary distributions. Since the class of processes expressible through such networks is big and only few assumptions are made, the principle also applies to other stochastic models. We give examples of interest from CRN theory to highlight the decomposition.

Exact maximal reduction of stochastic reaction networks by species lumping

Motivation Stochastic reaction networks are a widespread model to describe biological systems where the presence of noise is relevant, such as in cell regulatory processes. Unfortunately, in all but simplest models the resulting discrete state-space representation hinders analytical tractability and makes numerical simulations expensive. Reduction methods can lower complexity by computing model projections that preserve dynamics of interest to the user. Results We present an exact lumping method for stochastic reaction networks with mass-action kinetics. It hinges on an equivalence relation between the species, resulting in a reduced network where the dynamics of each macro-species is stochastically equivalent to the sum of the original species in each equivalence class, for any choice of the initial state of the system. Furthermore, by an appropriate encoding of kinetic parameters as additional species, the method can establish equivalences that do not depend on specific values of the parameters. The method is supported by an efficient algorithm to compute the largest species equivalence, thus the maximal lumping. The effectiveness and scalability of our lumping technique, as well as the physical interpretability of resulting reductions, is demonstrated in several models of signaling pathways and epidemic processes on complex networks. Availability and implementation The algorithms for species equivalence have been implemented in the software tool ERODE, freely available for download from https://www.erode.eu. Supplementary information Supplementary data are available at Bioinformatics online.

Stochastic reaction networks in dynamic compartment populations

Compartmentalization of biochemical processes underlies all biological systems, from the organelle to the tissue scale. Theoretical models to study the interplay between noisy reaction dynamics and compartmentalization are sparse, and typically very challenging to analyze computationally. Recent studies have made progress toward addressing this problem in the context of specific biological systems, but a general and sufficiently effective approach remains lacking. In this work, we propose a mathematical framework based on counting processes that allows us to study dynamic compartment populations with arbitrary interactions and internal biochemistry. We derive an efficient description of the dynamics in terms of differential equations which capture the statistics of the population. We demonstrate the relevance of our approach by analyzing models inspired by different biological processes, including subcellular compartmentalization and tissue homeostasis.

Quantifying Epigenetic Stability with Minimum Action Paths

Chromatin can adopt multiple stable, heritable states with distinct histone modifications and varying levels of gene expression. Insight on the stability and maintenance of such epigenetic states can be gained by mathematical modeling of stochastic reaction networks for histone modifications. Analytical results for the kinetic networks are particularly valuable. Compared to computationally demanding numerical simulations, they often are more convenient at evaluating the robustness of conclusions with respect to model parameters. In this communication, we developed a second-quantization based approach that can be used to analyze discrete stochastic models with a fixed, finite number of particles using a representation of the SU (2) algebra. We applied the approach to a kinetic model of chromatin states that captures the feedback between nucleosomes and the enzymes conferring histone modifications. Using a path integral expression for the transition probability, we computed the epigenetic landscape that helps to identify the emergence of bistability and the most probable path connecting the two steady states. We anticipate the generalizability of the approach will make it useful for studying more complicated models that couple epigenetic modifications with transcription factors and chromatin structure.