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Badal Joshi

Publications and source records attributed to Badal Joshi.

At least 19 recordsLinked to original sources

Instantaneous arithmetic computation via ratio-encoding in chemical reaction networks

We develop a general framework for instantaneous arithmetic computation using chemical reaction networks. Numerical values are encoded by ratios of species concentrations: an extended nonnegative value $a\in[0,+\infty]$ is represented by a computational pair $(A_0,A_1)$ through the ratio $a=a_1/a_0$. For this ratio encoding, our main theoretical result is a feedforward compositionality theorem: if a collection of modules satisfies two easily checked structural conditions, then any admissible finite feedforward composition computes the corresponding arithmetic expression instantaneously, meaning that every intermediate and output ratio is correct at every positive time. We make this framework concrete by constructing reaction network modules for four elementary operations---identification, inversion, multiplication, and addition---and verifying that each satisfies these structural conditions. As applications, we show that truncated power series and matrix products can be computed instantaneously using reaction networks whose size reflects the number of arithmetic operations in the underlying computation. We also extend the nonnegative ratio encoding to signed quantities by representing a real number as the difference of two nonnegative ratio-encoded values; this allows addition and multiplication over real-valued inputs. We discuss the practical implications of instantaneous computation, including its relationship to other resource constraints such as the number of chemical species required and the cost of reading out the final answer, which requires division and, in the signed case, rectified subtraction.

math.DS

Bistability, Absolute Concentration Robustness, and Hysteresis in Dual-Site Futile Cycles with Bifunctional Enzymes

Bifunctional enzymes, which catalyze both the forward and reverse steps of a substrate modification reaction, arise naturally in bacterial two-component signaling systems and metabolic regulation. Beyond their well-known role in conferring absolute concentration robustness (ACR) on substrate species, bifunctional enzymes profoundly shape the dynamical landscape of the networks in which they appear. We study a class of dual-site futile cycles in which the reverse modification steps are carried out by bifunctional enzyme-substrate compounds, and provide a complete mathematical analysis of all four such networks, characterizing the existence, number, and stability of steady states, as well as the bifurcation structure as total substrate is varied. All four networks admit boundary steady states, in contrast to the non-bifunctional case. The networks differ in the number and stability of boundary steady states, in the maximum number of positive steady states (ranging from two to four), and in whether bistability is present. In two networks, a transcritical bifurcation connects the boundary and positive steady state branches; in one case this is a backward bifurcation, producing hysteresis. Perhaps the most striking phenomenon occurs in one of the four networks, which simultaneously exhibits bistability and ACR in the final modification state, where the system can settle into either of two stable steady states with different intermediate concentrations yet identical final product concentration.

math.DS

Computing with reaction networks at input-independent speed: exponential and logarithmic functions

The concept of \textit{input-independent computational speed} for chemistry-based analog computers was introduced in Anderson-Joshi (2025), where it was shown that arithmetic operations can be computed with a convergence rate bounded below independently of the input values. Here, by inputs we mean the numerical values encoded by the initial concentrations of designated input species, with the underlying reaction network and rate constants held fixed. Combining these operations via power series to approximate transcendental functions is possible in principle, but the number of chemical species required grows with the number of terms retained, and achieving sufficient accuracy may demand many terms---a burden that is especially severe for slowly converging series such as the power series for the logarithm. In this paper, we begin the program of directly computing transcendental functions by chemical reaction networks by focusing on the exponential and logarithmic functions, two widely used transcendental functions, and constructing reaction network modules that compute them without relying on truncated power series. We show that the resulting modules are mass-action systems, and prove that they achieve arbitrary accuracy given sufficient time while operating at input-independent speed. Moreover, these modules can be combined with each other and with the arithmetic modules of Anderson-Joshi (2025): any such composite computation also runs at input-independent speed, with a convergence rate that does not depend on the length of the feedforward chain. Logarithm and exponential functions serve as foundational cases, and the constructions developed here are intended to serve as templates for the direct computation of more general transcendental functions by chemical reaction networks.

math.DS

Bifunctional enzyme action as a source of robustness in biochemical reaction networks: a novel hypergraph approach

Substrate modification networks are ubiquitous in living, biochemical systems. A higher-level hypergraph "skeleton" captures key information about which substrates are transformed in the presence of modification-specific enzymes. Many different detailed models can be associated to the same skeleton, however uncertainty related to model fitting increases with the level of detail. We show that essential dynamical properties such as existence of positive steady states and concentration robustness can be extracted directly from the skeleton independent of the detailed model. The novel formalism of directed hypergraphs is used to prove that bifunctional enzyme action plays a key role in generating robustness. Moreover, we use another novel concept of "current" on a directed hypergraph to establish a link between potentially remote network components. Current is an essential notion required for existence of positive steady states, and furthermore, current-matching combined with bifunctionality generates concentration robustness.

q-bio.MN

Chemical mass-action systems as analog computers: implementing arithmetic computations at specified speed

Recent technological advances allow us to view chemical mass-action systems as analog computers. In this context, the inputs to a computation are encoded as initial values of certain chemical species while the outputs are the limiting values of other chemical species. In this paper, we design chemical systems that carry out the elementary arithmetic computations of: identification, inversion, $m$th roots (for $m \ge 2$), addition, multiplication, absolute difference, rectified subtraction over non-negative real numbers, and partial real inversion over real numbers. We prove that these ``elementary modules'' have a speed of computation that is independent of the inputs to the computation. Moreover, we prove that finite sequences of such elementary modules, running in parallel, can carry out composite arithmetic over real numbers, also at a rate that is independent of inputs. Furthermore, we show that the speed of a composite computation is precisely the speed of the slowest elementary step. Specifically, the scale of the composite computation, i.e. the number of elementary steps involved in the composite, does not affect the overall asymptotic speed -- a feature of the parallel computing nature of our algorithm. Our proofs require the careful mathematical analysis of certain non-autonomous systems, and we believe this analysis will be useful in different areas of applied mathematics, dynamical systems, and the theory of computation. We close with a discussion on future research directions, including numerous important open theoretical questions pertaining to the field of computation with reaction networks.

math.DS

Bifunctional enzyme provides absolute concentration robustness in multisite covalent modification networks

Biochemical covalent modification networks exhibit a remarkable suite of steady state and dynamical properties such as multistationarity, oscillations, ultrasensitivity and absolute concentration robustness. This paper focuses on conditions required for a network to have a species with absolute concentration robustness. We find that the robustness in a substrate is endowed by its interaction with a bifunctional enzyme, which is an enzyme that has different roles when isolated versus when bound as a substrate-enzyme complex. When isolated, the bifunctional enzyme promotes production of more molecules of the robust species while when bound, the same enzyme facilitates degradation of the robust species. These dual actions produce robustness in the large class of covalent modification networks. For each network of this type, we find the network conditions for the presence of robustness, the species that has robustness, and its robustness value. The unified approach of simultaneously analyzing a large class of networks for a single property, i.e. absolute concentration robustness, reveals the underlying mechanism of the action of bifunctional enzyme while simultaneously providing a precise mathematical description of bifunctionality.

q-bio.MN

Prevalence of multistationarity and absolute concentration robustness in reaction networks

For reaction networks arising in systems biology, the capacity for two or more steady states, that is, multistationarity, is an important property that underlies biochemical switches. Another property receiving much attention recently is absolute concentration robustness (ACR), which means that some species concentration is the same at all positive steady states. In this work, we investigate the prevalence of each property while paying close attention to when the properties occur together. Specifically, we consider a stochastic block framework for generating random networks, and prove edge-probability thresholds at which - with high probability - multistationarity appears and ACR becomes rare. We also show that the small window in which both properties occur only appears in networks with many species. Taken together, our results confirm that, in random reversible networks, ACR and multistationarity together, or even ACR on its own, is highly atypical. Our proofs rely on two prior results, one pertaining to the prevalence of networks with deficiency zero, and the other "lifting" multistationarity from small networks to larger ones.

math.PR

Foundations of Static and Dynamic Absolute Concentration Robustness

Absolute Concentration Robustness (ACR) was introduced by Shinar and Feinberg as robustness of equilibrium species concentration in a mass action dynamical system. Their aim was to devise a mathematical condition that will ensure robustness in the function of the biological system being modeled. The robustness of function rests on what we refer to as empirical robustness -- the concentration of a species remains unvarying, when measured in the long run, across arbitrary initial conditions. Even simple examples show that the ACR notion introduced in Shinar and Feinberg (here referred to as static ACR) is neither necessary nor sufficient for empirical robustness. To make a stronger connection with empirical robustness, we define dynamic ACR, a property related to long-term, global dynamics, rather than only to equilibrium behavior. We discuss general dynamical systems with dynamic ACR properties as well as parametrized families of dynamical systems related to reaction networks. We find necessary and sufficient conditions for dynamic ACR in complex balanced reaction networks, a class of networks that is central to the theory of reaction networks.

math.DS

Power-engine-load form for dynamic absolute concentration robustness

In a reaction network, the concentration of a species with the property of dynamic absolute concentration robustness (dynamic ACR) converges to the same value independent of the overall initial values. This property endows a biochemical network with output robustness and therefore is essential for its functioning in a highly variable environment. It is important to identify structure of the dynamical system as well as constraints required for dynamic ACR. We propose a power-engine-load form of dynamic ACR and obtain results regarding convergence to the ACR value based on this form.

math.DS

Reaction Network Motifs for Static and Dynamic Absolute Concentration Robustness

Networks with absolute concentration robustness (ACR) have the property that a translation of a coordinate hyperplane either contains all steady states (static ACR) or attracts all trajectories (dynamic ACR). The implication for the underlying biological system is robustness in the concentration of one of the species independent of the initial conditions as well as independent of the concentration of all other species. Identifying network conditions for dynamic ACR is a challenging problem. We lay the groundwork in this paper by studying small reaction networks, those with 2 reactions and 2 species. We give a complete classification by ACR properties of these minimal reaction networks. The dynamics is rich even within this simple setting. Insights obtained from this work will help illuminate the properties of more complex networks with dynamic ACR.

math.DS

Multistationarity in cyclic sequestration-transmutation networks

We consider a natural class of reaction networks which consist of reactions where either two species can inactivate each other (i.e., sequestration), or some species can be transformed into another (i.e., transmutation), in a way that gives rise to a feedback cycle. We completely characterize the capacity of multistationarity of these networks. This is especially interesting because such networks provide simple examples of "atoms of multistationarity", i.e., minimal networks that can give rise to multiple positive steady states

math.DS

Transition graph decomposition for complex balanced reaction networks with non-mass-action kinetics

Reaction networks are widely used models to describe biochemical processes. Stochastic fluctuations in the counts of biological macromolecules have amplified consequences due to their small population sizes. This makes it necessary to favor stochastic, discrete population, continuous time models. The stationary distributions provide snapshots of the model behavior at the stationary regime, and as such finding their expression in terms of the model parameters is of great interest. The aim of the present paper is to describe when the stationary distributions of the original model, whose state space is potentially infinite, coincide exactly with the stationary distributions of the process truncated to finite subsets of states, up to a normalizing constant. The finite subsets of states we identify are called copies and are inspired by the modular topology of reaction network models. With such a choice we prove a novel graphical characterization of the concept of complex balancing for stochastic models of reaction networks. The results of the paper hold for the commonly used mass-action kinetics but are not restricted to it, and are in fact stated for more general setting.

math.PR

Autocatalytic Networks: An Intimate Relation between Network Topology and Dynamics

We study a family of networks of autocatalytic reactions, which we call hyperchains, that are a generalization of hypercycles. Hyperchains, and the associated dynamical system called replicator equations, are a possible mechanism for macromolecular evolution and proposed to play a role in abiogenesis, the origin of life from prebiotic chemistry. The same dynamical system also occurs in evolutionary game dynamics, genetic selection, and as Lotka-Volterra equations of ecology. An arrow in a hyperchain encapsulates the enzymatic influence of one species on the autocatalytic replication of another. We show that the network topology of a hyperchain, which captures all such enzymatic influences, is intimately related to the dynamical properties of the mass action system it generates. Dynamical properties such as existence, uniqueness and stability of a positive equilibrium as well as permanence, are determined by graph-theoretic properties such as existence of a spanning linear subgraph, being unrooted, being cyclic, and Hamiltonicity.

math.DS

On reaction network implementations of neural networks

This paper is concerned with the utilization of deterministically modeled chemical reaction networks for the implementation of (feed-forward) neural networks. We develop a general mathematical framework and prove that the ordinary differential equations (ODEs) associated with certain reaction network implementations of neural networks have desirable properties including (i) existence of unique positive fixed points that are smooth in the parameters of the model (necessary for gradient descent), and (ii) fast convergence to the fixed point regardless of initial condition (necessary for efficient implementation). We do so by first making a connection between neural networks and fixed points for systems of ODEs, and then by constructing reaction networks with the correct associated set of ODEs. We demonstrate the theory by constructing a reaction network that implements a neural network with a smoothed ReLU activation function, though we also demonstrate how to generalize the construction to allow for other activation functions (each with the desirable properties listed previously). As there are multiple types of "networks" utilized in this paper, we also give a careful introduction to both reaction networks and neural networks, in order to disambiguate the overlapping vocabulary in the two settings and to clearly highlight the role of each network's properties.

cs.NE

Autocatalytic systems and recombination: a reaction network perspective

Autocatalytic systems are very often incorporated in the "origin of life" models, a connection that has been analyzed in the context of the classical hypercycles introduced by Manfred Eigen. We investigate the dynamics of certain networks called bimolecular autocatalytic systems. In particular, we consider the dynamics corresponding to the relative populations in these networks, and show that they can be analyzed by studying well-chosen autonomous polynomial dynamical systems. Moreover, we find that one can use results from reaction network theory to prove persistence and permanence of several types of bimolecular autocatalytic systems called autocatalytic recombination networks.

math.DS

Detailed balance = complex balance + cycle balance. A graph-theoretic proof for reaction networks and Markov chains

We further clarify the relation between detailed-balanced and complex-balanced equilibria of reversible chemical reaction networks. Our results hold for arbitrary kinetics and also for boundary equilibria. Detailed balance, complex balance, "formal balance", and the new notion of "cycle balance" are all defined in terms of the underlying graph. This fact allows elementary graph-theoretic (non-algebraic) proofs of a previous result (detailed balance = complex balance + formal balance), our main result (detailed balance = complex balance + cycle balance), and a corresponding result in the setting of continuous-time Markov chains.

math.DS

Graphically balanced equilibria and stationary measures of reaction networks

The graph-related symmetries of a reaction network give rise to certain special equilibria (such as complex balanced equilibria) in deterministic models of dynamics of the reaction network. Correspondingly, in the stochastic setting, when modeled as a continuous-time Markov chain, these symmetries give rise to certain special stationary measures. Previous work by Anderson, Craciun and Kurtz identified stationary distributions of a complex balanced network; later Cappelletti and Wiuf developed the notion of complex balancing for stochastic systems. We define and establish the relations between reaction balanced measure, complex balanced measure, reaction vector balanced measure, and cycle balanced measure and prove that with mild additional hypotheses, the former two are stationary distributions. Furthermore, in spirit of earlier work by Joshi, we give sufficient conditions under which detailed balance of the stationary distribution of Markov chain models implies the existence of positive detailed balance equilibria for the related deterministic reaction network model. Finally, we provide a complete map of the implications between balancing properties of deterministic and corresponding stochastic reaction systems, such as complex balance, reaction balance, reaction vector balance and cycle balance.

math.PR

Which small reaction networks are multistationary?

Reaction networks taken with mass-action kinetics arise in many settings, from epidemiology to population biology to systems of chemical reactions. Bistable reaction networks are posited to underlie biochemical switches, which motivates the following question: which reaction networks have the capacity for multiple steady states? Mathematically, this asks: among certain parametrized families of polynomial systems, which admit multiple positive roots? No complete answer is known. This work analyzes the smallest networks, those with only a few chemical species or reactions. For these "smallest" networks, we completely answer the question of multistationarity and, in some cases, multistability too, thereby extending related work of Boros. Our results highlight the role played by the Newton polytope of a network (the convex hull of the reactant vectors). Also, our work is motivated by recent results that explain how a given network's capacity for multistationarity arises from that of certain related networks which are typically smaller. Hence, we are interested in classifying small multistationary networks, and our work forms a first step in this direction.

math.DS