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Annick Lesne

Publications and source records attributed to Annick Lesne.

15 recordsLinked to original sources

Radius selection using kernel density estimation for the computation of nonlinear measures

When nonlinear measures are estimated from sampled temporal signals with finite-length, a radius parameter must be carefully selected to avoid a poor estimation. These measures are generally derived from the correlation integral which quantifies the probability of finding neighbors, i.e. pair of points spaced by less than the radius parameter. While each nonlinear measure comes with several specific empirical rules to select a radius value, we provide a systematic selection method. We show that the optimal radius for nonlinear measures can be approximated by the optimal bandwidth of a Kernel Density Estimator (KDE) related to the correlation sum. The KDE framework provides non-parametric tools to approximate a density function from finite samples (e.g. histograms) and optimal methods to select a smoothing parameter, the bandwidth (e.g. bin width in histograms). We use results from KDE to derive a closed-form expression for the optimal radius. The latter is used to compute the correlation dimension and to construct recurrence plots yielding an estimate of Kolmogorov-Sinai entropy. We assess our method through numerical experiments on signals generated by nonlinear systems and experimental electroencephalographic time series.

stat.ME

Predicting attractors from spectral properties of stylized gene regulatory networks

How the architecture of gene regulatory networks ultimately shapes gene expression patterns is an open question, which has been approached from a multitude of angles. The dominant strategy has been to identify non-random features in these networks and then argue for the function of these features using mechanistic modelling. Here we establish the foundation of an alternative approach by studying the correlation of eigenvectors with synthetic gene expression data simulated with a basic and popular model of gene expression dynamics -- attractors of Boolean threshold dynamics in signed directed graphs. Eigenvectors of the graph Laplacian are known to explain collective dynamical states (stationary patterns) in Turing dynamics on graphs. In this study, we show that eigenvectors can also predict collective states (attractors) for a markedly different type of dynamics, Boolean threshold dynamics, and category of graphs, signed directed graphs. However, the overall predictive power depends on details of the network architecture, in a predictable fashion. Our results are a set of statistical observations, providing the first systematic step towards a further theoretical understanding of the role of eigenvectors in dynamics on graphs.

q-bio.MN

The 3D genome shapes the regulatory code of developmental genes

We revisit the notion of gene regulatory code in embryonic development in the light of recent findings about genome spatial organisation. By analogy with the genetic code, we posit that the concept of code can only be used if the corresponding adaptor can clearly be identified. An adaptor is here defined as an intermediary physical entity mediating the correspondence between codewords and objects in a gratuitous and evolvable way. In the context of the gene regulatory code, the encoded objects are the gene expression levels, while the concentrations of specific transcription factors in the cell nucleus provide the codewords. The notion of code is meaningful in the absence of direct physicochemical relationships between the objects and the codewords, when the mediation by an adaptor is required. We propose that a plausible adaptor for this code is the gene domain, that is, the genome segment delimited by topological insulators and comprising the gene and its enhancer regulatory sequences. We review recent evidences, based on genome-wide chromosome conformation capture experiments, showing that preferential contact domains found in metazoan genomes are the physical traces of gene domains. Accordingly, genome 3D folding plays a direct role in shaping the developmental gene regulatory code.

q-bio.GN

Kinetic signature of cooperativity in the irreversible collapse of a polymer

We investigate the kinetics of a polymer collapse due to the formation of irreversible crosslinks between its monomers. Using the contact probability $P(s)$ as a scale-dependent order parameter depending on the chemical distance $s$, our simulations show the emergence of a cooperative pearling instability. Namely, the polymer undergoes a sharp conformational transition to a set of absorbing states characterized by a length scale $ξ$ corresponding to the mean pearl size. This length and the transition time depend on the polymer equilibrium dynamics and the crosslinking rate. We confirm experimentally this transition using a DNA conformation capture experiment in yeast.

cond-mat.soft

The physics of epigenetics

In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multi-scale physical mechanisms that govern the biological processes behind the initiation, spreading and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional ones, such as the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of non-equilibrium dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature under this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping and transmitting this crucial "epigenetic landscape". This new perspective not only allows to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.

physics.bio-ph

A Physical Model for the Condensation and Decondensation of Eukaryotic Chromosomes

During the eukaryotic cell cycle, chromatin undergoes several conformational changes, which are believed to play key roles in gene expression regulation during interphase, and in genome replication and division during mitosis. In this paper, we propose a scenario for chromatin structural reorganization during mitosis, which bridges all the different scales involved in chromatin architecture, from nucleosomes to chromatin loops. We build a model for chromatin, based on available data, taking into account both physical and topological constraints DNA has to deal with. Our results suggest that the mitotic chromosome condensation/decondensation process is induced by a structural change at the level of the nucleosome itself.

q-bio.SC

Hamiltonian model of heat conductivity and Fourier law

We investigate the stationary nonequilibrium states of a quasi one-dimensional system of heavy particles whose interaction is mediated by purely elastic collisions with light particles, in contact at the boundary with two heat baths with fixed temperatures $T^+$ and $T^-$. It is shown that Fourier law is satisfied with a thermal conductivity proportional to $\sqrt{T(x)}$ where $T(x)$ is the local temperature. Entropy flux and entropy production are also investigated.

cond-mat.stat-mech

Constructing and exploring wells of energy landscapes

Landscape paradigm is ubiquitous in physics and other natural sciences, but it has to be supplemented with both quantitative and qualitatively meaningful tools for analyzing the topography of a given landscape. We here consider dynamic explorations of the relief and introduce as basic topographic features ``wells of duration $T$ and altitude $y$''. We determine an intrinsic exploration mechanism governing the evolutions from an initial state in the well up to its rim in a prescribed time, whose finite-difference approximations on finite grids yield a constructive algorithm for determining the wells. Our main results are thus (i) a quantitative characterization of landscape topography rooted in a dynamic exploration of the landscape, (ii) an alternative to stochastic gradient dynamics for performing such an exploration, (iii) a constructive access to the wells and (iv) the determination of some bare dynamic features inherent to the landscape. The mathematical tools used here are not familiar in physics: They come from set-valued analysis (differential calculus of set-valued maps and differential inclusions) and viability theory (capture basins of targets under evolutionary systems) which have been developed during the last two decades; we therefore propose a minimal appendix exposing them at the end of this paper to bridge the possible gap.

cond-mat.stat-mech

From discrete to continuous dynamics and back: How large is 1?

Discrete autonomous dynamical systems in dimension 1 can exhibit chaotic behavior, whereas the corresponding continuous evolution equations rule it out, and cannot even possess a nontrivial periodic solution. Therefore the passage from discrete to continuous equations (and conversely) is all but harmless. We address this issue and evidence some caveats on the paradigmatic Verhulst logistic equation, investigating in particular the status and influence of the actual size of the unit time step in discrete modelings, rooted in well-known numerical analysis.

cond-mat.other

Adaptive elastic properties of chromatin fiber

Chromatin is a complex of DNA and specific proteins forming an intermediary level of organization of eukaryotic genomes, between double-stranded DNA and chromosome. Within a generic modeling of the chromatin assembly, we investigate the interplay between the mechanical properties of the chromatin fiber and its biological functions. A quantitative step is to relate the mechanics at the DNA level and the mechanics described at the chromatin fiber level. It allows to calculate the complete set of chromatin elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant), in terms of DNA elastic properties and geometric features of the fiber. These elastic constants are strongly sensitive to the local architecture of the fiber and we argue that this tunable elasticity might be a key feature in chromatin functions, for instance in the initiation and regulation of transcription. Moreover, this analysis provides a framework to interpret micromanipulations studies of chromatin fiber and suggests further experiments involving intercalators to scan the tunable elasticity of the fiber.

cond-mat.stat-mech

Intercalation and buckling instability of DNA linker within locked chromatin fiber

The chromatin fiber is a complex of DNA and specific proteins called histones forming the first structural level of organization of eukaryotic chromosomes. In tightly organized chromatin fibers, the short segments of naked DNA linking the nucleosomes are strongly end constrained. Longitudinal thermal fluctuations in these linkers allow intercalative mode of protein binding. We show that mechanical constraints generated in the first stage of the binding process induce linker DNA buckling; buckling in turn modifies the binding energies and activation barriers and creates a force of decondensation at the chromatin fiber level. The unique structure and properties of DNA thus yield a novel physical mechanism of buckling instability that might play a key role in the regulation of gene expression.

cond-mat.stat-mech

Deterministic motion of the controversial piston in the thermodynamic limit

We consider the evolution of a system composed of $N$ non-interacting point particles of mass $m$ in a cylindrical container divided into two regions by a movable adiabatic wall (the adiabatic piston). We study the thermodynamic limit for the piston where the area $A$ of the cross-section, the mass $M$ of the piston, and the number $N$ of particles go to infinity keeping $A/M$ and $N/M$ fixed. The length of the container is a fixed parameter which can be either finite or infinite. In this thermodynamic limit we show that the motion of the piston is deterministic and the evolution is adiabatic. Moreover if the length of the container is infinite, we show that the piston evolves toward a stationary state with velocity approximately proportional to the pressure difference. If the length of the container is finite, introducing a simplifying assumption we show that the system evolves with either weak or strong damping toward a well-defined state of mechanical equilibrium where the pressures are the same, but the temperatures different. Numerical simulations are presented to illustrate possible evolutions and to check the validity of the assumption.

cond-mat.stat-mech

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.

cond-mat.soft

Anomalous tricritical behaviour in the coil-globule transition of a single polymer chain

We investigate a model of self-avoiding walk exhibiting a first-order coil-globule transition. This first-order nature, unravelled through the coexistence of distinct coil and globule populations, has observable consequences on the scaling properties. A thorough analysis of the size dependence of the mean radius of gyration evidences a breakdown of the plain tricritical scaling behaviour. In some regimes, anomalous exponents are observed in the transition region and logarithmic corrections arise along the coexistence curve.

cond-mat.stat-mech

First-order theta-point of a single polymer chain

Conformational transitions of a single macromolecule of finite size $N$ cannot be described within standard thermodynamic framework. Taking as a basis a simple model of homopolymer exhibiting a coil-globule transition, we show that a relevant approach is to describe the thermal equilibrium distribution $P_N^{(β)}(t)$ of some variable $t$ characterizing the conformation. Although the mean order parameter exhibits a second-order behaviour in the infinite-size limit, the $Θ$-point arises from the coexistence of two distinct populations, associated with two well-separated peaks of $P_N^{(β)}(t)$ and identified respectively with a coil state and a globule state. Remarkably, this first-order feature increases with the size of the chain. It allows to describe the transition within a two-state model, well-suited to analyse experimental data.

cond-mat.stat-mech