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Philippe Robert

Publications and source records attributed to Philippe Robert.

At least 19 recordsLinked to original sources
arXiv2026

Thermodynamic Limits of Stochastic Chemical Reaction Networks with Phosphorylation

In this paper we investigate the stability properties of a fundamental mechanism of biological cells called phosphorylation. The system is a chemical reaction network (CRN) for which a chemical species, {\em the substrate}, can be sequentially transformed into two phosphorylated forms, by the activity of two types of enzymes, one type for phosphorylation, the other for dephosphorylation. We investigate a stochastic representation of this model, under the mass action kinetics. The total mass of the substrate is fixed at $N$, while the total mass of enzymes scales proportionally to $N$. The asymptotic behavior, when $N$ is large, of the concentrations of all chemical species is studied. We investigate the possible {\em stable} subsets of chemical species for the kinetics of the law of mass action. A stable subset is such that, with a convenient initial state, the number of copies of the species of this subset remains $O(1)$ on any finite time interval as $N$ gets large. The role of the twelve reaction rate constants, {\em the catalytic constants} of the CRN, is investigated from this point of view. An averaging principle of the corresponding Markov process is established for several regimes of the CRN. It is shown in particular that there exists a regime with three equilibrium points, with two of them stable. The proofs of the results rely on stochastic calculus with Poisson processes, convenient couplings of subsets of coordinates of the Markov process, technical results on $M/M/\infty$ queues, and a stability analysis of a dynamical system in $\mathbb{R}_+^4$.

math.PR↗
arXiv2025

Stochastic Models of Resource Allocation in Chemical Reaction Networks

This paper analyses of a stochastic model of a chemical reaction network with three types of chemical species ${\cal R}$, ${\cal M}$ and ${\cal U}$ that interact to transform a flow of external resources, the chemical species ${\cal Q}$, to produce a product, the chemical species ${\cal P}_r$. A regulation mechanism involving the sequestration of the chemical species ${\cal R}$ when the flow of resources is too low is investigated. The original motivation of the study is of analyzing the qualitative properties of a key regulation mechanism of gene expression in biological cells, the {\em stringent response}. A scaling analysis of a Markov process in $\N^5$ representing the state of the chemical reaction network is achieved. It is shown that, depending on the parameters of the model, there are, quite surprisingly, three possible asymptotic regimes. To each of them corresponds a stochastic averaging principle with a fast process expressed in terms of a network of $M/M/\infty$ queues. One of these regimes, the optimal sequestration regime, does not seem to have been identified up to now. Under this regime, the input flow of resources is low but the state of the network is still acceptable in terms of unused macro-molecules, showing the remarkable efficiency of this regulation mechanism. The technical proofs of the main convergence results rely on a combination of coupling arguments, technical estimates of the solutions of SDEs, of sample paths of fast processes in particular, and the stability properties of some dynamical systems in $\R^2$.

math.PR↗
arXiv2025

Improving Virtual Contrast Enhancement using Longitudinal Data

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to enhance lesion detection and characterisation, particularly in the field of neuro-oncology. Nevertheless, concerns regarding gadolinium retention and accumulation in brain and body tissues, most notably for diseases that require close monitoring and frequent GBCA injection, have led to the need for strategies to reduce dosage. In this study, a deep learning framework is proposed for the virtual contrast enhancement of full-dose post-contrast T1-weighted MRI images from corresponding low-dose acquisitions. The contribution of the presented model is its utilisation of longitudinal information, which is achieved by incorporating a prior full-dose MRI examination from the same patient. A comparative evaluation against a non-longitudinal single session model demonstrated that the longitudinal approach significantly improves image quality across multiple reconstruction metrics. Furthermore, experiments with varying simulated contrast doses confirmed the robustness of the proposed method. These results emphasize the potential of integrating prior imaging history into deep learning-based virtual contrast enhancement pipelines to reduce GBCA usage without compromising diagnostic utility, thus paving the way for safer, more sustainable longitudinal monitoring in clinical MRI practice.

eess.IV↗
arXiv2024

Analysis of Stochastic Chemical Reaction Networks with a Hierarchy of Timescales

We investigate a class of stochastic chemical reaction networks with $n{\ge}1$ chemical species $S_1$, \ldots, $S_n$, and whose complexes are only of the form $k_iS_i$, $i{=}1$,\ldots, $n$, where $(k_i)$ are integers. The time evolution of these CRNs is driven by the kinetics of the law of mass action. A scaling analysis is done when the rates of external arrivals of chemical species are proportional to a large scaling parameter $N$. A natural hierarchy of fast processes, a subset of the coordinates of $(X_i(t))$, is determined by the values of the mapping $i{\mapsto}k_i$. We show that the scaled vector of coordinates $i$ such that $k_i{=}1$ and the scaled occupation measure of the other coordinates are converging in distribution to a deterministic limit as $N$ gets large. The proof of this result is obtained by establishing a functional equation for the limiting points of the occupation measure, by an induction on the hierarchy of timescales and with relative entropy functions.

math.PR↗
arXiv2024

Stochastic Chemical Reaction Networks with Discontinuous Limits and AIMD processes

In this paper we study a class of stochastic chemical reaction networks (CRNs) for which chemical species are created by a sequence of chain reactions. We prove that under some convenient conditions on the initial state, some of these networks exhibit a discrete-induced transitions (DIT) property: isolated, random, events have a direct impact on the macroscopic state of the process. If this phenomenon has already been noticed in several CRNs, in auto-catalytic networks in the literature of physics in particular, there are up to now few rigorous studies in this domain. A scaling analysis of several cases of such CRNs with several classes of initial states is achieved. The DIT property is investigated for the case of a CRN with four nodes. We show that on the normal timescale and for a subset of (large) initial states and for convenient Skorohod topologies, the scaled process converges in distribution to a Markov process with jumps, an Additive Increase/Multiplicative Decrease (AIMD) process. This asymptotically discontinuous limiting behavior is a consequence of a DIT property due to random, local, blowups of jumps occurring during small time intervals. With an explicit representation of invariant measures of AIMD processes and time-change arguments, we show that, with a speed-up of the timescale, the scaled process is converging in distribution to a continuous deterministic function. The DIT analyzed in this paper is connected to a simple chain reaction between three chemical species and is therefore likely to be a quite generic phenomenon for a large class of CRNs.

math.PR↗
arXiv2023

A Stochastic Analysis of Particle Systems with Pairing

Motivated by a general principle governing regulation mechanisms in biological cells, we investigate a general interaction scheme between different populations of particles and specific particles, referred to as agents. Assuming that each particle follows a random path in the medium, when a particle and an agent meet, they may bind and form a pair which has some specific functional properties. Such a pair is also subject to random events and it splits after some random amount of time. In a stochastic context, using a Markovian model for the vector of the number of paired particles, and by taking the total number of particles as a scaling parameter, we study the asymptotic behavior of the time evolution of the number of paired particles. Two scenarios are investigated: one with a large but fixed number of agents, and the other one, the dynamic case, when agents are created at a bounded rate and may die after some time when they are not paired. A first order limit theorem is established for the time evolution of the system in both cases. The proof of an averaging principle of the dynamic case is one of the main contributions of the paper. Limit theorems for fluctuations are obtained in the case of a fixed number agents. The impact of dynamical arrivals of agents on the level of pairing of the system is discussed.

math.PR↗
arXiv2023

Scaling Methods for Stochastic Chemical Reaction Networks

The asymptotic properties of some Markov processes associated to stochastic chemical reaction networks (CRNs) driven by the kinetics of the law of mass action are analyzed. The scaling regime introduced in the paper assumes that the norm of the initial state is converging to infinity. The reaction rate constants are kept fixed. The purpose of the paper is of showing, with simple examples, a scaling analysis in this context. The main difference with the scalings of the literature is that it does not change the graph structure of the CRN or its reaction rates. Several CRNs are investigated to illustrate the insight that can be gained on the qualitative properties of these networks. A detailed scaling analysis of a CRN with several interesting asymptotic properties, with a bi-modal behavior in particular, is worked out in the last section. Additionally, with several examples, we also show that a stability criterion due to Filonov for positive recurrence of Markov processes may simplify significantly the stability analysis of these networks.

math.PR↗
arXiv2022

A Palm Space Approach to Non-Linear Hawkes Processes

A Hawkes process on $\R$ is a point process whose intensity function at time $t$ is a functional of its past activity before time $t$. It is defined by its activation function $\Phi$ and its memory function $h$. In this paper, the Hawkes property is expressed as an operator on the sub-space of non-negative sequences associated to distances between its points. By using the classical correspondence between a stationary point process and its Palm measure, we establish a characterization of the corresponding Palm measure as an invariant distribution of a Markovian kernel. We prove that if $\Phi$ is continuous and its growth rate is at most linear with a rate below some constant, then there exists a stationary Hawkes point process. The classical Lipschitz condition of the literature for an unbounded function $\Phi$ is relaxed. Our proofs rely on a combination of coupling methods, monotonicity properties of linear Hawkes processes and classical results on Palm distributions. An investigation of the Hawkes process starting from the null measure, the empty state, on $\R_-$ plays also an important role. The linear case of Hawkes and Oakes is revisited at this occasion. If the memory function $h$ is an exponential function, under a weak condition it is shown that there exists a unique stationary Hawkes point process. In this case, its Palm measure is expressed in terms of the invariant distribution of a one-dimensional Harris ergodic Markov chain. When the activation function is a polynomial $\Phi$ with degree ${>}1$, there does not exist a stationary Hawkes process and if the Hawkes process starts from the empty state, a scaling result for the accumulation of its points is obtained.

math.PR↗
arXiv2022

Stochastic Models of Regulation of Transcription in Biological Cells

In this paper we study an important global regulation mechanism of transcription of biological cells using specific macro-molecules, 6S RNAs. The functional property of 6S RNAs is of blocking the transcription of RNAs when the environment of the cell is not favorable. We investigate the efficiency of this mechanism with a scaling analysis of a stochastic model. The evolution equations of our model are driven by the law of mass action and the total number of polymerases is used as a scaling parameter. Two regimes are analyzed: exponential phase when the environment of the cell is favorable to its growth, and the stationary phase when resources are scarce. In both regimes, by defining properly occupation measures of the model, we prove an averaging principle for the associated multi-dimensional Markov process on a convenient timescale, as well as convergence results for fast variables of the system. An analytical expression of the asymptotic fraction of sequestrated polymerases in stationary phase is in particular obtained. The consequences of these results are discussed.

math.PR↗
arXiv2021

Stochastic Models of Neural Plasticity: A Scaling Approach

In neuroscience, synaptic plasticity refers to the set of mechanisms driving the dynamics of neuronal connections, called synapses and represented by a scalar value, the synaptic weight. A Spike-Timing Dependent Plasticity (STDP) rule is a biologically-based model representing the time evolution of the synaptic weight as a functional of the past spiking activity of adjacent neurons. A general mathematical framework has been introduced in~arXiv:2010.08195. In this paper we develop and investigate a scaling approach of these models based on several biological assumptions. Experiments show that long-term synaptic plasticity evolves on a much slower timescale than the cellular mechanisms driving the activity of neuronal cells, like their spiking activity or the concentration of various chemical components created/suppressed by this spiking activity. For this reason, a scaled version of the stochastic model of~arXiv:2010.08195 is introduced and a limit theorem, an averaging principle, is stated for a large class of plasticity kernels. A companion paper~arXiv:2010.08790 is entirely devoted to the tightness properties used to prove these convergence results. These averaging principles are used to study two important STDP models: pair-based rules and calcium-based rules. Our results are compared with the approximations of neuroscience STDP models. A class of discrete models of STDP rules is also investigated for the analytical tractability of its limiting dynamical system.

math.PR↗
arXiv2021

On the Spontaneous Dynamics of Synaptic Weights in Stochastic Models with Pair-Based STDP

We investigate spike-timing dependent plasticity (STPD) in the case of a synapse connecting two neural cells. We develop a theoretical analysis of several STDP rules using Markovian theory. In this context there are two different timescales, fast neural activity and slower synaptic weight updates. Exploiting this timescale separation, we derive the long-time limits of a single synaptic weight subject to STDP. We show that the pairing model of presynaptic and postsynaptic spikes controls the synaptic weight dynamics for small external input, on an excitatory synapse. This result implies in particular that mean-field analysis of plasticity may miss some important properties of STDP. Anti-Hebbian STDP seems to favor the emergence of a stable synaptic weight, but only for high external input. In the case of inhibitory synapse the pairing schemes matter less, and we observe convergence of the synaptic weight to a non-null value only for Hebbian STDP. We extensively study different asymptotic regimes for STDP rules, raising interesting questions for future works on adaptative neural networks and, more generally, on adaptive systems.

q-bio.NC↗
arXiv2021

Stochastic Models of Neural Synaptic Plasticity

In neuroscience, learning and memory are usually associated to long-term changes of neuronal connectivity. In this context, synaptic plasticity refers to the set of mechanisms driving the dynamics of neuronal connections, called {\em synapses} and represented by a scalar value, the synaptic weight. Spike-Timing Dependent Plasticity (STDP) is a biologically-based model representing the time evolution of the synaptic weight as a functional of the past spiking activity of adjacent neurons. If numerous models of neuronal cells have been proposed in the mathematical literature, few of them include a variable for the time-varying strength of the connection. A new, general, mathematical framework is introduced to study synaptic plasticity associated to different STDP rules. The system composed of two neurons connected by a single synapse is investigated and a stochastic process describing its dynamical behavior is presented and analyzed. The notion of plasticity kernel is introduced as a key component of plastic neural networks models, generalizing a notion used for pair-based models. We show that a large number of STDP rules from neuroscience and physics can be represented by this formalism. Several aspects of these models are discussed and compared to canonical models of computational neuroscience. An important sub-class of plasticity kernels with a Markovian formulation is also defined and investigated. In these models, the time evolution of cellular processes such as the neuronal membrane potential and the concentrations of chemical components created/suppressed by spiking activity has the Markov property.

math.PR↗
arXiv2020

Averaging Principles for Markovian Models of Plasticity

Mathematical models of biological neural networks are associated to a rich and complex class of stochastic processes. In this paper, we consider a simple {\em plastic} neural network whose {\em connectivity/synaptic strength} $(W(t))$ depends on a set of activity-dependent processes to model {\em synaptic plasticity}, a well-studied mechanism from neuroscience. A general class of stochastic models has been introduced in \cite{robert_mathematical_2020} to study the stochastic process $(W(t))$. It has been observed experimentally that its dynamics occur on much slower timescale than that of the main cellular processes. The purpose of this paper is to establish limit theorems for the distribution of $(W(t))$ with respect to the fast timescale of neuronal processes. The central result of the paper is an averaging principle for the stochastic process $(W(t))$. Mathematically, the key variable is the point process whose jumps occur at the instants of neuronal spikes. A thorough analysis of several of its unbounded additive functionals is achieved in the slow-fast limit. Additionally, technical results on interacting shot-noise processes are developed and used in the general proof of the averaging principle.

math.PR↗
arXiv2020

Models of protein production along the cell cycle: an investigation of possible sources of noise

In this article, we quantitatively study, through stochastic models, the efects of several intracellular phenomena, such as cell volume growth, cell division, gene replication as well as fuctuations of available RNA polymerases and ribosomes. These phenomena are indeed rarely considered in classic models of protein production and no relative quantitative comparison among them has been performed. The parameters for a large and representative class of proteins are determined using experimental measures. The main important and surprising conclusion of our study is to show that despite the signifcant fuctuations of free RNA polymerases and free ribosomes, they bring little variability to protein production contrary to what has been previously proposed in the literature. After verifying the robustness of this quite counter-intuitive result, we discuss its possible origin from a theoretical view, and interpret it as the result of a mean-feld efect.

q-bio.MN↗
arXiv2019

Mathematical Models of Gene Expression

In this paper we analyze the equilibrium properties of a large class of stochastic processes describing the fundamental biological process within bacterial cells, {\em the production process of proteins}. Stochastic models classically used in this context to describe the time evolution of the numbers of mRNAs and proteins are presented and discussed. An extension of these models, which includes elongation phases of mRNAs and proteins, is introduced. A convergence result to equilibrium for the process associated to the number of proteins and mRNAs is proved and a representation of this equilibrium as a functional of a Poisson process in an extended state space is obtained. Explicit expressions for the first two moments of the number of mRNAs and proteins at equilibrium are derived, generalizing some classical formulas. Approximations used in the biological literature for the equilibrium distribution of the number of proteins are discussed and investigated in the light of these results. Several convergence results for the distribution of the number of proteins at equilibrium are in particular obtained under different scaling assumptions.

q-bio.MN↗
arXiv2019

Monotonic Gaussian Process for Spatio-Temporal Disease Progression Modeling in Brain Imaging Data

We introduce a probabilistic generative model for disentangling spatio-temporal disease trajectories from series of high-dimensional brain images. The model is based on spatio-temporal matrix factorization, where inference on the sources is constrained by anatomically plausible statistical priors. To model realistic trajectories, the temporal sources are defined as monotonic and time-reparametrized Gaussian Processes. To account for the non-stationarity of brain images, we model the spatial sources as sparse codes convolved at multiple scales. The method was tested on synthetic data favourably comparing with standard blind source separation approaches. The application on large-scale imaging data from a clinical study allows to disentangle differential temporal progression patterns mapping brain regions key to neurodegeneration, while revealing a disease-specific time scale associated to the clinical diagnosis.

stat.ML↗
arXiv2018

Robust Point Light Source Estimation Using Differentiable Rendering

Illumination estimation is often used in mixed reality to re-render a scene from another point of view, to change the color/texture of an object, or to insert a virtual object consistently lit into a real video or photograph. Specifically, the estimation of a point light source is required for the shadows cast by the inserted object to be consistent with the real scene. We tackle the problem of illumination retrieval given an RGBD image of the scene as an inverse problem: we aim to find the illumination that minimizes the photometric error between the rendered image and the observation. In particular we propose a novel differentiable renderer based on the Blinn-Phong model with cast shadows. We compare our differentiable renderer to state-of-the-art methods and demonstrate its robustness to an incorrect reflectance estimation.

cs.CV↗