arXiv subjects

José A. Cuesta

Publications and source records attributed to José A. Cuesta.

At least 19 recordsLinked to original sources

arXiv2026

Optimization of sequential therapies to maximize extinction of resistant bacteria through collateral sensitivity

Antimicrobial resistance (AMR) threatens global health. A promising and underexplored strategy to tackle this problem is sequential therapies exploiting collateral sensitivity (CS), whereby resistance to one drug increases sensitivity to another. Here, we develop a four-genotype stochastic birth-death model with two bacteriostatic antibiotics to identify switching periods that maximize bacterial extinction under subinhibitory concentrations. We show that extinction probability depends nonlinearly on switching period, with stepwise increases aligned to discrete switch events: fast sequential therapies are suboptimal as they do not allow for the evolution of resistance, a key ingredient in these therapies. A geometric distribution framework accurately predicts cumulative extinction probabilities, where the per-switch extinction probability rises with switching period. We further derive a heuristic approximation for the extinction probability based on times to fixation of single-resistant mutants. Sensitivity analyses reveal that strong reciprocal CS is required for this strategy to work, and we explore how increasing antibiotic doses and higher mutation rates modulate extinction in a nonmonotonic manner. Finally, we discuss how longer therapies maximize extinction but also cause higher resistance, leading to a Pareto front of optimal switching periods. Our results provide quantitative design principles for in vitro and clinical sequential antibiotic therapies, underscoring the potential of CS-guided regimens to suppress resistance evolution and eradicate infections.

q-bio.PE↗

arXiv2026

A generative model for bipartite gene-sharing networks

Gene-sharing networks provide a powerful framework to study the evolution of viruses and mobile genetic elements. These bipartite networks, which link genes to the genomes that contain them, exhibit characteristic degree distributions: a scale-free distribution for genes and an exponential-like decay for genomes. Here, we propose a mechanistic model that explains these patterns through fundamental evolutionary processes including horizontal gene transfer, capture of new genes, emergence of new genomes, and gene loss. Using a mean-field approximation, we derive analytical expressions for the asymptotic gene and genome degree distributions, recapitulating a power-law distribution for genes and an exponential distribution for genomes. Numerical simulations validate these predictions and yield parameter values that closely fit empirical data from dsDNA viruses, RNA viruses, and prokaryotic pangenomes. This simple model with only two parameters provides a generative framework for bipartite gene-sharing networks, offering qualitative and quantitative insights into the main evolutionary forces driving genome plasticity. Setting the gene loss rate to zero, the gene and genome degree distributions of the model closely fit the empirically observed distributions. Thus, evolution of viruses appears to be dominated by gene gain, in agreement with the results of independent reconstructions of viral evolution.

q-bio.PE↗

arXiv2026

Beyond the Central Limit: Universality of the Gamma Distribution from Padé-Enhanced Large Deviations

The central limit theorem provides the theoretical foundation for the universality of the normal distribution: under broad conditions, the asymptotic distribution of a sum of independent random variables approaches a Gaussian. Yet, physical systems described by positive random variable -- from earthquakes to microbial growth to epidemic spreading -- consistently exhibit gamma rather than Gaussian statistics -- what leads to field-specific mechanistic explanations that are non robust to small changes in the model details. We show that gamma distributions emerge naturally from large deviation theory when Padé approximants replace polynomial expansions of the derivative of the scaled cumulant generating function, respecting positivity constraints that the central limit theorem violates. Gamma universality thus emerges as the constrained analog of Gaussian universality, providing a mechanism-free explanation for its pervasive appearance across different disciplines.

physics.data-an↗

arXiv2026

Microbiome association diversity reflects proximity to the edge of instability

Recent advances in metagenomics have revealed macroecological patterns or "laws" describing robust statistical regularities across microbial communities. Stochastic logistic models (SLMs), which treat species as independent -- akin to ideal gases in physics -- and incorporate environmental noise, reproduce many single-species patterns but cannot account for the pairwise covariation observed in microbiome data. Here we introduce an interacting stochastic logistic model (ISLM) that minimally extends the SLM by sampling an ensemble of random interaction networks chosen to preserve these single-species laws. Using dynamical mean-field theory, we map the model's phase diagram -- stable, chaotic, and unbounded-growth regimes -- where the transition from stable fixed-point to chaos is controlled by network sparsity and interaction heterogeneity via a May-like instability line. Going beyond mean-field theory to account for finite communities, we derive an estimator of an effective stability parameter that quantifies distance to the edge of instability and can be inferred from the width of the distribution of pairwise covariances in empirical species-abundance data. Applying this framework to synthetic data, environmental microbiomes, and human gut cohorts indicates that these communities tend to operate near the edge of instability. Moreover, gut communities from healthy individuals cluster closer to this edge and exhibit broader, more heterogeneous associations, whereas dysbiosis-associated states shift toward more stable regimes -- enabling discrimination across conditions such as Crohn's disease, inflammatory bowel syndrome, and colorectal cancer. Together, our results connect macroecological laws, interaction-network ensembles, and May's stability theory, suggesting that complex communities may benefit from operating near a dynamical phase transition.

q-bio.PE↗

arXiv2026

The challenge of scale in molecular adaptation: Local searches in astronomical genotype networks

The exploration of vast genotype spaces poses fundamental challenges for evolving populations. As the number of genotypes encoding viable phenotypes grows exponentially with genome length, populations can only explore a tiny fraction of these immense spaces, a fact consistently supported by empirical and theoretical evidence. Paradoxically, local, mutation-driven searches near abundant sequences allow populations to generate phenotypic improvements and functional innovations despite this immense search space. In this contribution, we integrate insights from viral evolution with theoretical expectations derived from genotype-phenotype maps to re-examine how high-dimensional sequence spaces shape evolutionary dynamics. In resolving the paradox, abundant phenotypes play a crucial role because their combinatorial weight biases evolutionary trajectories. We discuss how this bias, together with limited accessibility of fitness peaks, modifies traditional metaphors -- such as fitness landscapes -- and challenges standard notions of evolutionary optimality. Our results underscore that adaptation is predominantly local yet remarkably efficient, providing a unifying perspective on the coexistence of robustness, innovation, and constrained exploration in molecular evolution.

q-bio.PE↗

arXiv2025

Scarce Data, Noisy Inferences, and Overfitting: The Hidden Flaws in Ecological Dynamics Modelling

Metagenomic data has significantly advanced microbiome research by employing ecological models, particularly in personalised medicine. The generalised Lotka-Volterra (gLV) model is commonly used to understand microbial interactions and predict ecosystem dynamics. However, gLV models often fail to capture complex interactions, especially when data is limited or noisy. This study critically assesses the effectiveness of gLV and similar models using Bayesian inference and a model reduction method based on information theory. We found that ecological data often leads to non-interpretability and overfitting due to limited information, noisy data, and parameter sloppiness. Our results highlight the need for simpler models that align with the available data and propose a distribution-based approach to better capture ecosystem diversity, stability, and competition. These findings challenge current bottom-up ecological modelling practices and aim to shift the focus toward a Statistical Mechanics view of ecology based on distributions of parameters.

q-bio.PE↗

arXiv2024

Non-equilibrium microbial dynamics unveil a new macroecological pattern beyond Taylor's law

We introduce a comprehensive analytical benchmark, relying on Fokker-Planck formalism, to study microbial dynamics in presence of both biotic and abiotic forces. In equilibrium, we observe a balance between the two kinds of forces, leading to no correlations between species abundances. This implies that real microbiomes, where correlations have been observed, operate out of equilibrium. Therefore, we analyze non-equilibrium dynamics, presenting an ansatz for an approximate solution that embodies the complex interplay of forces in the system. This solution is consistent with Taylor's law as a coarse-grained approximation of the relation between species abundance and variance, but implies subtler effects, predicting unobserved structure beyond Taylor's law. Motivated by this theoretical prediction, we refine the analysis of existing metagenomic data, unveiling a novel universal macroecological pattern. Finally, we speculate on the physical origin of Taylor's law: building upon an analogy with Brownian motion theory, we propose that Taylor's law emerges as a Fluctuation-Growth relation resulting from equipartition of environmental resources among microbial species.

q-bio.PE↗

arXiv2023

Sparse species interactions reproduce abundance correlation patterns in microbial communities

During the last decades macroecology has identified broad-scale patterns of abundances and diversity of microbial communities and put forward some potential explanations for them. However, these advances are not paralleled by a full understanding of the dynamical processes behind them. In particular, abundance fluctuations of different species are found to be correlated, both across time and across communities in metagenomic samples. Reproducing such correlations through appropriate population models remains an open challenge. The present paper tackles this problem and points to sparse species interactions as a necessary mechanism to account for them. Specifically, we discuss several possibilities to include interactions in population models and recognize Lotka-Volterra constants as a successful ansatz. For this, we design a Bayesian inference algorithm to extract sets of interaction constants able to reproduce empirical probability distributions of pairwise correlations for diverse biomes. Importantly, the inferred models still reproduce well-known single-species macroecological patterns concerning abundance fluctuations across both species and communities. Endorsed by the agreement with the empirically observed phenomenology, our analyses provide insights on the properties of the networks of microbial interactions, revealing that sparsity is a crucial feature.

q-bio.PE↗

arXiv2023

Stability of the personal relationship networks in a longitudinal study of middle school students

The personal network of relationships is structured in circles of friendships, that go from the most intense relationships to the least intense ones. While this is a well established result, little is known about the stability of those circles and their evolution in time. To shed light on this issue, we study the temporal evolution of friendships among teenagers during two consecutive academic years by means of a survey administered on five occasions. We show that the first two circles, best friends and friends, can be clearly observed in the survey but also that being in one or the other leads to more or less stable relationships. We find that being in the same class is one of the key drivers of friendship evolution. We also observe an almost constant degree of reciprocity in the relationships, around 60%, a percentage influenced both by being in the same class and by gender homophily. Not only do our results confirm the mounting evidence supporting the circle structure of human social networks, but they also show that these structures persist in time despite the turnover of individual relationships -- a fact that may prove particularly useful for understanding the social environment in middle schools.

physics.soc-ph↗

arXiv2023

Entropic contribution to phenotype fitness

All possible phenotypes are not equally accessible to evolving populations. In fact, only phenotypes of large size, i.e. those resulting from many different genotypes, are found in populations of sequences, presumably because they are easier to discover and maintain. Genotypes that map to these phenotypes usually form mostly connected genotype networks that percolate the space of sequences, thus guaranteeing access to a large set of alternative phenotypes. Within a given environment, where specific phenotypic traits become relevant for adaptation, the replicative ability of a phenotype and its overall fitness (in competition experiments with alternative phenotypes) can be estimated. Two primary questions arise: how do phenotype size, reproductive capability and topology of the genotype network affect the fitness of a phenotype? And, assuming that evolution is only able to access large phenotypes, what is the range of unattainable fitness values? In order to address these questions, we quantify the adaptive advantage of phenotypes of varying size and spectral radius in a two-peak landscape. We derive analytical relationships between the three variables (size, topology, and replicative ability) which are then tested through analysis of genotype-phenotype maps and simulations of population dynamics on such maps. Finally, we analytically show that the fraction of attainable phenotypes decreases with the length of the genotype, though its absolute number increases. The fact that most phenotypes are not visible to evolution very likely forbids the attainment of the highest peak in the landscape. Nevertheless, our results indicate that the relative fitness loss due to this limited accessibility is largely inconsequential for adaptation.

q-bio.PE↗

arXiv2022

Free-energy density functional for Strauss's model of transitive networks

Ensemble models of graphs are one of the most important theoretical tools to study complex networks. Among them, exponential random graphs (ERGs) have proven to be very useful in the analysis of social networks. In this paper we develop a technique, borrowed from the statistical mechanics of lattice gases, to solve Strauss's model of transitive networks. This model was introduced long ago as an ERG ensemble for networks with high clustering and exhibits a first-order phase transition above a critical value of the triangle interaction parameter, where two different kinds of networks with different densities of links (or, alternatively, different clustering) coexist. Compared to previous mean-field approaches, our method describes accurately even small networks and can be extended beyond Strauss's classical model -- e.g. to networks with different types of nodes. This allows us to tackle, for instance, models with node homophily. We provide results for the latter and show that they accurately reproduce the outcome of Monte Carlo simulations.

cond-mat.stat-mech↗

arXiv2022

Prevalence of mutualism in a simple model of microbial co-evolution

Evolutionary transitions among ecological interactions are widely known, although their detailed dynamics remain absent for most population models. Adaptive dynamics has been used to illustrate how the parameters of population models might shift through evolution, but within an ecological regime. Here we use adaptive dynamics combined with a generalised logistic model of population dynamics to show that transitions of ecological interactions might appear as a consequence of evolution. To this purpose we introduce a two-microbial toy model in which population parameters are determined by a bookkeeping of resources taken from (and excreted to) the environment, as well as from the byproducts of the other species. Despite its simplicity, this model exhibits all kinds of potential ecological transitions, some of which resemble those found in nature. Overall, the model shows a clear trend toward the emergence of mutualism.

q-bio.PE↗

arXiv2022

Beyond Dunbar circles: a continuous description of social relationships and resource allocation

We discuss the structure of human relationship patterns in terms of a new formalism that allows to study resource allocation problems where the cost of the resource may take continuous values. This is in contrast with the main focus of previous studies where relationships were classified in a few, discrete layers (known as Dunbar's circles) with the cost being the same within each layer. We show that with our continuum approach we can identify a parameter $η$ that is the equivalent of the ratio of relationships between adjacent circles in the discrete case, with a value $η\sim 6$. We confirm this prediction using three different datasets coming from phone records, face-to-face contacts, and interactions in Facebook. As the sample size increases, the distributions of estimated parameters smooth around the predicted value of $η$. The existence of a characteristic value of the parameter at the population level indicates that the model is capturing a seemingly universal feature on how humans manage relationships. Our analyses also confirm earlier results showing the existence of social signatures arising from having to allocate finite resources into different relationships, and that the structure of online personal networks mirrors those in the off-line world.

physics.soc-ph↗

arXiv2021

From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics

Understanding how genotypes map onto phenotypes, fitness, and eventually organisms is arguably the next major missing piece in a fully predictive theory of evolution. We refer to this generally as the problem of the genotype-phenotype map. Though we are still far from achieving a complete picture of these relationships, our current understanding of simpler questions, such as the structure induced in the space of genotypes by sequences mapped to molecular structures, has revealed important facts that deeply affect the dynamical description of evolutionary processes. Empirical evidence supporting the fundamental relevance of features such as phenotypic bias is mounting as well, while the synthesis of conceptual and experimental progress leads to questioning current assumptions on the nature of evolutionary dynamics-cancer progression models or synthetic biology approaches being notable examples. This work delves into a critical and constructive attitude in our current knowledge of how genotypes map onto molecular phenotypes and organismal functions, and discusses theoretical and empirical avenues to broaden and improve this comprehension. As a final goal, this community should aim at deriving an updated picture of evolutionary processes soundly relying on the structural properties of genotype spaces, as revealed by modern techniques of molecular and functional analysis.

q-bio.PE↗

arXiv2020

Predictability: Can the turning point and end of an expanding epidemic be precisely forecast?

No, they can't. Epidemic spread is characterized by exponentially growing dynamics, which are intrinsically unpredictable. The time at which the growth in the number of infected individuals halts and starts decreasing cannot be calculated with certainty before the turning point is actually attained; neither can the end of the epidemic after the turning point. An SIR model with confinement (SCIR) illustrates how lockdown measures inhibit infection spread only above a threshold that we calculate. The existence of that threshold has major effects in predictability: A Bayesian fit to the COVID-19 pandemic in Spain shows that a slow-down in the number of newly infected individuals during the expansion phase allows to infer neither the precise position of the maximum nor whether the measures taken will bring the propagation to the inhibition regime. There is a short horizon for reliable prediction, followed by a dispersion of the possible trajectories that grows extremely fast. The impossibility to predict in the mid-term is not due to wrong or incomplete data, since it persists in error-free, synthetically produced data sets, and does not necessarily improve by using larger data sets. Our study warns against precise forecasts of the evolution of epidemics based on mean-field, effective or phenomenological models, and supports that only probabilities of different outcomes can be confidently given.

q-bio.PE↗

arXiv2020

Hierarchical clustering of bipartite data sets based on the statistical significance of coincidences

When some 'entities' are related by the 'features' they share they are amenable to a bipartite network representation. Plant-pollinator ecological communities, co-authorship of scientific papers, customers and purchases, or answers in a poll, are but a few examples. Analyzing clustering of such entities in the network is a useful tool with applications in many fields, like internet technology, recommender systems, or detection of diseases. The algorithms most widely applied to find clusters in bipartite networks are variants of modularity optimization. Here we provide an hierarchical clustering algorithm based on a dissimilarity between entities that quantifies the probability that the features shared by two entities is due to mere chance. The algorithm performance is $O(n^2)$ when applied to a set of n entities, and its outcome is a dendrogram exhibiting the connections of those entities. Through the introduction of a 'susceptibility' measure we can provide an 'optimal' choice for the clustering as well as quantify its quality. The dendrogram reveals further useful structural information though -- like the existence of sub-clusters within clusters or of nodes that do not fit in any cluster. We illustrate the algorithm by applying it first to a set of synthetic networks, and then to a selection of examples. We also illustrate how to transform our algorithm into a valid alternative for one-mode networks as well, and show that it performs at least as well as the standard, modularity-based algorithms -- with a higher numerical performance. We provide an implementation of the algorithm in Python freely accessible from GitHub.

cs.SI↗

arXiv2019

Epistasis between cultural traits drives paradigm shifts in cultural evolution

Every now and then the cultural paradigm of a society changes. Human history can be regarded as a sequence of long periods of cultural stasis punctuated by paradigm shifts that transform culture upside-down over the turn of a few generations. We propose here a population dynamics model devised to analyse paradigm shifts. In this model individuals are defined by a vector of cultural traits that can change mainly through imitation of other individuals' traits. The novelty of the model is that cultural traits may interact reinforcing or hindering each other. Imitation is then biased by the 'cultural fitness' landscape thus defined. Our main result is that abrupt paradigm shifts occur, as a response to weak changes in the landscape, only when cultural traits do interact---whereas adaptation is smooth if there is no interaction. Borrowing the genetic term, this interaction is called 'cultural epistasis'. The result is robust to the way that epistasis is implemented, to whether imitation is biased by homophily, or to changes in other model parameters. Finally, a relevant consequence of this dynamics is the irreversible nature of paradigm shifts: the old paradigm cannot be restored even if the external changes are undone. Our model puts the phenomenon of paradigm shifts in cultural evolution in the same category as catastrophic shifts in ecology or phase transitions in physics.

physics.soc-ph↗

arXiv2018

Statistical theory of phenotype abundance distributions: a test through exact enumeration of genotype spaces

The evolutionary dynamics of molecular populations are strongly dependent on the structure of genotype spaces. The map between genotype and phenotype determines how easily genotype spaces can be navigated and the accessibility of evolutionary innovations. In particular, the size of neutral networks corresponding to specific phenotypes and its statistical counterpart, the distribution of phenotype abundance, have been studied through multiple computationally tractable genotype-phenotype maps. In this work, we test a theory that predicts the abundance of a phenotype and the corresponding asymptotic distribution (given the compositional variability of its genotypes) through the exact enumeration of several GP maps. Our theory predicts with high accuracy phenotype abundance, and our results show that, in navigable genotype spaces ---characterised by the presence of large neutral networks---, phenotype abundance converges to a log-normal distribution.

q-bio.PE↗