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Pedro Pessoa

Publications and source records attributed to Pedro Pessoa.

18 recordsLinked to original sources

Allostery Beyond Amplification: Temporal Regulation of Signaling Information

Allostery is a fundamental mechanism of protein regulation and is commonly interpreted as modulating enzymatic activity or product abundance. Here we show that this view is incomplete. Using a stochastic model of allosteric regulation combined with an information-theoretic analysis, we quantify the mutual information between an enzyme's regulatory state and the states of downstream signaling components. Beyond controlling steady-state production levels, allostery also regulates the timing and duration over which information is transmitted. By tuning the temporal operating regime of signaling pathways, allosteric regulation enables distinct dynamical outcomes from identical molecular components, providing a physical mechanism for temporal information flow, signaling specificity, and coordination without changes in metabolic pathways.

q-bio.MN

Inherited or produced? Inferring protein production kinetics when protein counts are shaped by a cell's division history

Inferring protein production kinetics for dividing cells is complicated due to protein inheritance from the mother cell. For instance, fluorescence measurements -- commonly used to assess gene activation -- may reflect not only newly produced proteins but also those inherited through successive cell divisions. In such cases, observed protein levels in any given cell are shaped by its division history. As a case study, we examine activation of the glc3 gene in yeast involved in glycogen synthesis and expressed under nutrient-limiting conditions. We monitor this activity using snapshot fluorescence measurements via flow cytometry, where GFP expression reflects glc3 promoter activity. A na\"ive analysis of flow cytometry data ignoring cell division suggests many cells are active with low expression. Explicitly accounting for the (non-Markovian) effects of cell division and protein inheritance makes it impossible to write down a tractable likelihood -- a key ingredient in physics-inspired inference, defining the probability of observing data given a model. The dependence on a cell's division history breaks the assumptions of standard (Markovian) master equations, rendering traditional likelihood-based approaches inapplicable. Instead, we adapt conditional normalizing flows (a class of neural network models designed to learn probability distributions) to approximate otherwise intractable likelihoods from simulated data. In doing so, we find that glc3 is mostly inactive under stress, showing that while cells occasionally activate the gene, expression is brief and transient.

q-bio.QM

Mamba time series forecasting with uncertainty quantification

State space models, such as Mamba, have recently garnered attention in time series forecasting due to their ability to capture sequence patterns. However, in electricity consumption benchmarks, Mamba forecasts exhibit a mean error of approximately 8\%. Similarly, in traffic occupancy benchmarks, the mean error reaches 18\%. This discrepancy leaves us to wonder whether the prediction is simply inaccurate or falls within error given spread in historical data. To address this limitation, we propose a method to quantify the predictive uncertainty of Mamba forecasts. Here, we propose a dual-network framework based on the Mamba architecture for probabilistic forecasting, where one network generates point forecasts while the other estimates predictive uncertainty by modeling variance. We abbreviate our tool, Mamba with probabilistic time series forecasting, as Mamba-ProbTSF and the code for its implementation is available on GitHub (https://github.com/PessoaP/Mamba-ProbTSF). Evaluating this approach on synthetic and real-world benchmark datasets, we find Kullback-Leibler divergence between the learned distributions and the data--which, in the limit of infinite data, should converge to zero if the model correctly captures the underlying probability distribution--reduced to the order of $10^{-3}$ for synthetic data and $10^{-1}$ for real-world benchmark, demonstrating its effectiveness. We find that in both the electricity consumption and traffic occupancy benchmark, the true trajectory stays within the predicted uncertainty interval at the two-sigma level about 95\% of the time. We end with a consideration of potential limitations, adjustments to improve performance, and considerations for applying this framework to processes for purely or largely stochastic dynamics where the stochastic changes accumulate, as observed for example in pure Brownian motion or molecular dynamics trajectories.

stat.ML

Avoiding subtraction and division of stochastic signals using normalizing flows: NFdeconvolve

Across the scientific realm, we find ourselves subtracting or dividing stochastic signals. For instance, consider a stochastic realization, $x$, generated from the addition or multiplication of two stochastic signals $a$ and $b$, namely $x=a+b$ or $x = ab$. For the $x=a+b$ example, $a$ can be fluorescence background and $b$ the signal of interest whose statistics are to be learned from the measured $x$. Similarly, when writing $x=ab$, $a$ can be thought of as the illumination intensity and $b$ the density of fluorescent molecules of interest. Yet dividing or subtracting stochastic signals amplifies noise, and we ask instead whether, using the statistics of $a$ and the measurement of $x$ as input, we can recover the statistics of $b$. Here, we show how normalizing flows can generate an approximation of the probability distribution over $b$, thereby avoiding subtraction or division altogether. This method is implemented in our software package, NFdeconvolve, available on GitHub with a tutorial linked in the main text.

stat.ML

Perspectives: Comparison of Deep Learning Segmentation Models on Biophysical and Biomedical Data

Deep learning based approaches are now widely used across biophysics to help automate a variety of tasks including image segmentation, feature selection, and deconvolution. However, the presence of multiple competing deep learning architectures, each with its own unique advantages and disadvantages, makes it challenging to select an architecture best suited for a specific application. As such, we present a comprehensive comparison of common models. Here, we focus on the task of segmentation assuming the typically small training dataset sizes available from biophysics experiments and compare the following four commonly used architectures: convolutional neural networks, U-Nets, vision transformers, and vision state space models. In doing so, we establish criteria for determining optimal conditions under which each model excels, thereby offering practical guidelines for researchers and practitioners in the field.

eess.IV

Avoiding matrix exponentials for large transition rate matrices

Exact methods for exponentiation of matrices of dimension $N$ can be computationally expensive in terms of execution time ($N^{3}$) and memory requirements ($N^{2}$) not to mention numerical precision issues. A type of matrix often exponentiated in the sciences is the rate matrix. Here we explore five methods to exponentiate rate matrices some of which apply even more broadly to other matrix types. Three of the methods leverage a mathematical analogy between computing matrix elements of a matrix exponential and computing transition probabilities of a dynamical processes (technically a Markov jump process, MJP, typically simulated using Gillespie). In doing so, we identify a novel MJP-based method relying on restricting the number of "trajectory" jumps based on the magnitude of the matrix elements with favorable computational scaling. We then discuss this method's downstream implications on mixing properties of Monte Carlo posterior samplers. We also benchmark two other methods of matrix exponentiation valid for any matrix (beyond rate matrices and, more generally, positive definite matrices) related to solving differential equations: Runge-Kutta integrators and Krylov subspace methods. Under conditions where both the largest matrix element and the number of non-vanishing elements scale linearly with $N$ -- reasonable conditions for rate matrices often exponentiated -- computational time scaling with the most competitive methods (Krylov and one of the MJP-based methods) reduces to $N^2$ with total memory requirements of $N$.

physics.chem-ph

Information geometry and Bose-Einstein condensation

It is a long held conjecture in the connection between information geometry (IG) and thermodynamics that the curvature endowed by IG diverges at phase transitions. Recent work on the IG of Bose-Einstein (BE) gases challenged this conjecture by saying that in the limit of fugacity approaching unit -- where BE condensation is expected -- curvature does not diverge, rather it converges to zero. However, as the discontinuous behavior that identify condensation is only observed at the thermodynamic limit, a study of IG curvature at finite number of particles, $N$, is in order from which the thermodynamic behaviour can be observed by taking the thermodynamic limit ($N\to \infty$) posteriorly. This article presents such study, which was made possible by the recent advances presented in [Phys. Rev. A 104, 043318 (2021)]. We find that for a trapped gas, as $N$ increases, the values of curvature decrease proportionally to a power of $N$ while the temperature at which the maximum value of curvature occurs approaches the usually defined critical temperature. This means that, in the thermodynamic limit, curvature has a limited value where a phase transition is observed, contradicting the forementioned conjecture.

cond-mat.quant-gas

How many submissions does it take to discover friendly suggested reviewers?

It is ever more common in scientific publishing to ask authors to suggest some reviewers for their own manuscripts. The question then arises: How many submissions does it take to discover friendly suggested reviewers? To answer this question, we present an agent-based simulation of (single-blinded) peer review, followed by a Bayesian classification of suggested reviewers. To set a lower bound on the number of submissions possible, we create a optimistically simple model that should allow us to more readily deduce the degree of friendliness of the reviewer. Despite this model's optimistic conditions, we find that one would need hundreds of submissions to classify even a small reviewer subset. Thus, it is virtually unfeasible under realistic conditions. This ensures that the peer review system is sufficiently robust to allow authors to suggest their own reviewers.

stat.AP

Revisiting Claims in "Black Hole Entropy: A Closer Look"

Here we explain how C. Tsallis' reply (Entropy 2021, 23(5), 630) fails to respond to points raised in (Entropy 2020, 22(10), 1110) and introduces further inconsistencies on the origin of black hole entropy. In his reply, Tsallis argues that the extensivity of thermodynamical entropy with respect to chosen variables needs to be preserved. Consequently the entropy functional is inadequate for black holes. Here we explain the undesirable consequences of this reasoning on black hole thermodynamics.

gr-qc

Bose-Einstein statistics for a finite number of particles

This article presents a study of the grand canonical Bose-Einstein (BE) statistics for a finite number of particles in an arbitrary quantum system. The thermodynamical quantities that identify BE condensation -- namely, the fraction of particles in the ground state and the specific heat -- are calculated here exactly in terms of temperature and fugacity. These calculations are complemented by a numerical calculation of fugacity in terms of the number of particles, without taking the thermodynamic limit. The main advantage of this approach is that it does not rely on approximations made in the vicinity of the usually defined critical temperature, rather it makes calculations with arbitrary precision possible, irrespective of temperature. Graphs for the calculated thermodynamical quantities are presented in comparison to the results previously obtained in the thermodynamic limit. In particular, it is observed that for the gas trapped in a 3-dimensional box the derivative of specific heat reaches smaller values than what was expected in the thermodynamic limit -- here, this result is also verified with analytical calculations. This is an important result for understanding the role of the thermodynamic limit in phase transitions and makes possible to further study BE statistics without relying neither on the thermodynamic limit nor on approximations near critical temperature.

cond-mat.quant-gas

Statistical Mechanics of Unconfined Systems: Challenges and Lessons

Motivated by applications of statistical mechanics in which the system of interest is spatially unconfined, we present an exact solution to the maximum entropy problem for assigning a stationary probability distribution on the phase space of an unconfined ideal gas in an anti-de Sitter background. Notwithstanding the gas's freedom to move in an infinite volume, we establish necessary conditions for the stationary probability distribution to be normalizable. As a part of our analysis, we develop a novel method for identifying dynamical constraints based on local measurements. With no appeal to \emph{a priori} information about globally-defined conserved quantities, it is thereby applicable to a much wider range of problems.

cond-mat.stat-mech

Legendre transformation and information geometry for the maximum entropy theory of ecology

Here I investigate some mathematical aspects of the maximum entropy theory of ecology (METE). In particular I address the geometrical structure of METE endowed by information geometry. As novel results, the macrostate entropy is calculated analytically by the Legendre transformation of the log-normalizer in METE. This result allows for the calculation of the metric terms in the information geometry arising from METE and, by consequence, the covariance matrix between METE variables.

q-bio.PE

Entropic dynamics yields reciprocal relations

Entropic dynamics is a framework for defining dynamical systems that is aligned with the principles of information theory. In an entropic dynamics model for motion on a statistical manifold, we find that the rate of changes for expected values is linear to the gradient of entropy with reciprocal (symmetric) coefficients. Reciprocity principles have been useful in physics since Onsager. Here we show how the entropic dynamics reciprocity is a consequence of the information geometric structure of the exponential family, hence it is a general property that can be extended to a broader class of dynamical models.

math.DS

Entropic dynamics on Gibbs statistical manifolds

Entropic dynamics is a framework in which the laws of dynamics are derived as an application of entropic methods of inference. Its successes include the derivation of quantum mechanics and quantum field theory from probabilistic principles. Here we develop the entropic dynamics of a system the state of which is described by a probability distribution. Thus, the dynamics unfolds on a statistical manifold which is automatically endowed by a metric structure provided by information geometry. The curvature of the manifold has a significant influence. We focus our dynamics on the statistical manifold of Gibbs distributions (also known as canonical distributions or the exponential family). The model includes an "entropic" notion of time that is tailored to the system under study; the system is its own clock. As one might expect, entropic time is intrinsically directional; there is a natural arrow of time which is lead by entropic considerations. As illustrative examples we discuss dynamics on a space of Gaussians and the discrete 3-state system.

cond-mat.stat-mech

Entropic Dynamics of Networks

Here we present the entropic dynamics formalism for networks. That is, a framework for the dynamics of graphs meant to represent a network derived from the principle of maximum entropy and the rate of transition is obtained taking into account the natural information geometry of probability distributions. We apply this framework to the Gibbs distribution of random graphs obtained with constraints on the node connectivity. The information geometry for this graph ensemble is calculated and the dynamical process is obtained as a diffusion equation. We compare the steady state of this dynamics to degree distributions found on real-world networks.

physics.soc-ph

Information geometry for Fermi-Dirac and Bose-Einstein quantum statistics

Information geometry is an emergent branch of probability theory that consists of assigning a Riemannian differential geometry structure to the space of probability distributions. We present an information geometric investigation of gases following the Fermi-Dirac and the Bose-Einstein quantum statistics. For each quantum gas, we study the information geometry of the curved statistical manifolds associated with the grand canonical ensemble. The Fisher-Rao information metric and the scalar curvature are computed for both fermionic and bosonic models of non-interacting particles. In particular, by taking into account the ground state of the ideal bosonic gas in our information geometric analysis, we find that the singular behavior of the scalar curvature in the condensation region disappears. This is a counterexample to a long held conjecture that curvature always diverges in phase transitions.

quant-ph

Comment on "Black Hole Entropy: A Closer Look"

In a recent paper [Entropy 2020, 22(1), 17] C. Tsallis states that entropy -- as in Shannon's or Kullback-Leiber's definitions -- is inadequate to interpret black hole entropy and suggests that a new non-additive functional should take the role of entropy. Here we counter argue by explaining the important distinction between the properties of extensivity and additivity, the latter is fundamental for entropy while the former is a property of particular thermodynamical systems that is not expected on black holes. We also point out other debatable statements in his analysis of black hole entropy.

gr-qc

Exact Renormalization Groups as a form of Entropic Dynamics

The Renormalization Group (RG) is a set of methods that have been instrumental in tackling problems involving an infinite number of degrees of freedom. What all these methods have in common -- which is what explains their success -- is that they allow a systematic search for those degrees of freedom that happen to be relevant to the phenomena in question. In the standard approaches the RG transformations are implemented by either coarse graining or by changes of variables. When these transformations are infinitesimal the formalism can be described as a continuous dynamical flow in a fictitious time parameter. It is generally the case that these exact RG equations are functional diffusion equations. In this paper we show that the exact RG equations can be derived using entropic methods. The RG flow is then described as a form of entropic dynamics of field configurations. Although equivalent to other versions of the RG, in this approach the RG transformations receive a purely inferential interpretation that establishes a clear link to information theory.

cond-mat.stat-mech