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Sudam Surasinghe

Publications and source records attributed to Sudam Surasinghe.

8 recordsLinked to original sources

Learning virulence-transmission relationships using causal inference

The relationship between traits that influence pathogen virulence and transmission is part of the central canon of the evolution and ecology of infectious disease. However, identifying directional and mechanistic relationships among traits remains a key challenge in various subfields of biology, as models often assume static, fixed links between characteristics. Here, we introduce learning evolutionary trait relationships (LETR), a data-driven framework that applies Granger-causality principles to determine which traits drive others and how these relationships change over time. LETR integrates causal discovery with generative mapping and transfer-operator analysis to link short-term predictability with long-term trait distributions. Using a synthetic myxomatosis virus-host data set, we show that LETR reliably recovers known directional influences, such as virulence driving transmission. Applying the framework to global pandemic (SARS-CoV-2) data, we find that past virulence improves future transmission prediction, while the reverse effect is weak. Invariant-density estimates reveal a long-term trend toward low virulence and transmission, with bimodality in virulence suggesting ecological influences or host heterogeneity. In summary, this study provides a blueprint for learning the relationship between how harmful a pathogen is and how well it spreads, which is highly idiosyncratic and context-dependent. This finding undermines simplistic models and encourages the development of new theory for the constraints underlying pathogen evolution. Further, by uniting causal inference with dynamical modeling, the LETR framework offers a general approach for uncovering mechanistic trait linkages in complex biological systems of various kinds.

q-bio.PE

Optimal virulence strategies in epidemiological models with asymptomatic transmission

Asymptomatic infection has gained notoriety as an important feature of infectious disease dynamics. Despite increasing attention, there have been few rigorous examinations of how asymptomatic transmission influences pathogen evolution. In this study, we apply evolutionary invasion analysis to compute optimal strategies for viruses evolving in a system with a distinct asymptomatic transmission stage. We ask how pathogens would evolve under three conditions: with an increase in the mean infectious period in the symptomatic state, with an increase in the mean infectious period in the asymptomatic stage, and an increase in proportion proceeding through the ``mild recovery route" (where the symptomatic state was bypassed entirely). We find that an increased proportion of cases moving through a ``mild recovery route" -- which can occur with different host susceptibility or increased public health intervention -- leads to a model structure in which mutant pathogens are transmitted largely through the asymptomatic route, with slightly increased evolved virulence levels. In addition, we find that an increase in the mean infectious period of the symptomatic state has a small overall influence on the fitness of the pathogen, when effective transmission can occur via the asymptomatic route. Further, we find that virulence levels change very slightly for both the asymptomatic and symptomatic populations. In sum, our results highlight the evolutionary implications of variation in host susceptibility and public health interventions in the context of asymptomatic transmission. More generally, the findings speak to the need for more nuanced interrogations of subtle routes of transmission, as they can have profound implications in disease evolution, ecology, and epidemiology.

q-bio.PE

Structural causal influence (SCI) captures the forces of social inequality in models of disease dynamics

Mathematical modeling has played a central role in understanding how infectious disease transmission manifests in populations. These models have demonstrated the importance of key community-level factors in structuring epidemic risk, and are now routinely used in public health for decision support. One barrier to their broader utility is that the existing canon does not often accommodate social inequalities as distinct formal drivers of variability in transmission dynamics. Given decades of evidence supporting the organizational effects of inequalities in structuring society more generally, and infectious disease risk more specifically, addressing this modeling gap is of critical importance. In this study, we build on previous efforts to integrate social forces into computational epidemiology by introducing a metric, the structural causal influence (SCI). The SCI uses causal analysis to provide a measure of the relative vulnerability of sub-communities within a susceptible population, shaped by differences in characteristics such as access to therapy, exposure to disease, and other determinants driven by social forces. We develop our metric in a simple case and apply it to a context of public health importance: Hepatitis C virus in a population of persons who inject drugs. In addition, we demonstrate the flexibility of the SCI using an agent-based model of an infectious disease. Our use of the SCI reveals that, under specific parameters in a multi-community model, the "less vulnerable" community may achieve a basic reproduction number below one, ensuring disease extinction. However, even minimal transmission between communities can increase this number, leading to sustained epidemics within both communities.

q-bio.QM

The context-specificity of virulence evolution revealed through evolutionary invasion analysis

Models are often employed to integrate knowledge about epidemics across scales and simulate disease dynamics. While these approaches have played a central role in studying the mechanics underlying epidemics, we lack ways to reliably predict how the relationship between virulence (the harm to hosts caused by an infection) and transmission will evolve in certain virus-host contexts. In this study, we invoke evolutionary invasion analysis -- a method used to identify the evolution of uninvadable strategies in dynamical systems -- to examine how the virulence-transmission dichotomy can evolve in models of virus infections defined by different natural histories. We reveal that peculiar ecologies drive different evolved relationships between virulence and transmission. Specifically, we discover patterns of virulence evolution between epidemics of various kinds (SARS-CoV-2 and hepatitis C virus) and that varying definitions of virulence alter our predictions for how viruses will evolve. We discuss the findings in light of contemporary conversations in the public health sector around the possibility of predicting virus evolution and in more extensive theoretical discussions involving virulence evolution in emerging infectious diseases.

q-bio.PE

Analysis of tidal flows through the Strait of Gibraltar using Dynamic Mode Decomposition

The Strait of Gibraltar is a region characterized by intricate oceanic sub-mesoscale features, influenced by topography, tidal forces, instabilities, and nonlinear hydraulic processes, all governed by the nonlinear equations of fluid motion. In this study, we aim to uncover the underlying physics of these phenomena within 3D MIT general circulation model simulations, including waves, eddies, and gyres. To achieve this, we employ Dynamic Mode Decomposition (DMD) to break down simulation snapshots into Koopman modes, with distinct exponential growth/decay rates and oscillation frequencies. Our objectives encompass evaluating DMD's efficacy in capturing known features, unveiling new elements, ranking modes, and exploring order reduction. We also introduce modifications to enhance DMD's robustness, numerical accuracy, and robustness of eigenvalues. DMD analysis yields a comprehensive understanding of flow patterns, internal wave formation, and the dynamics of the Strait of Gibraltar, its meandering behaviors, and the formation of a secondary gyre, notably the Western Alboran Gyre, as well as the propagation of Kelvin and coastal-trapped waves along the African coast. In doing so, it significantly advances our comprehension of intricate oceanographic phenomena and underscores the immense utility of DMD as an analytical tool for such complex datasets, suggesting that DMD could serve as a valuable addition to the toolkit of oceanographers.

math.DS

Learning Transfer Operators by Kernel Density Estimation

Inference of transfer operators from data is often formulated as a classical problem that hinges on the Ulam method. The conventional description, known as the Ulam-Galerkin method, involves projecting onto basis functions represented as characteristic functions supported over a fine grid of rectangles. From this perspective, the Ulam-Galerkin approach can be interpreted as density estimation using the histogram method. In this study, we recast the problem within the framework of statistical density estimation. This alternative perspective allows for an explicit and rigorous analysis of bias and variance, thereby facilitating a discussion on the mean square error. Through comprehensive examples utilizing the logistic map and a Markov map, we demonstrate the validity and effectiveness of this approach in estimating the eigenvectors of the Frobenius-Perron operator. We compare the performance of Histogram Density Estimation(HDE) and Kernel Density Estimation(KDE) methods and find that KDE generally outperforms HDE in terms of accuracy. However, it is important to note that KDE exhibits limitations around boundary points and jumps. Based on our research findings, we suggest the possibility of incorporating other density estimation methods into this field and propose future investigations into the application of KDE-based estimation for high-dimensional maps. These findings provide valuable insights for researchers and practitioners working on estimating the Frobenius-Perron operator and highlight the potential of density estimation techniques in this area of study. Keywords: Transfer Operators; Frobenius-Perron operator; probability density estimation; Ulam-Galerkin method; Kernel Density Estimation; Histogram Density Estimation.

cs.LG

Randomized Projection Learning Method forDynamic Mode Decomposition

A data-driven analysis method known as dynamic mode decomposition (DMD) approximates the linear Koopman operator on projected space. In the spirit of Johnson-Lindenstrauss Lemma, we will use random projection to estimate the DMD modes in reduced dimensional space. In practical applications, snapshots are in high dimensional observable space and the DMD operator matrix is massive. Hence, computing DMD with the full spectrum is infeasible, so our main computational goal is estimating the eigenvalue and eigenvectors of the DMD operator in a projected domain. We will generalize the current algorithm to estimate a projected DMD operator. We focus on a powerful and simple random projection algorithm that will reduce the computational and storage cost. While clearly, a random projection simplifies the algorithmic complexity of a detailed optimal projection, as we will show, generally the results can be excellent nonetheless, and quality understood through a well-developed theory of random projections. We will demonstrate that modes can be calculated for a low cost by the projected data with sufficient dimension. Keyword: Koopman Operator, Dynamic Mode Decomposition(DMD), Johnson-Lindenstrauss Lemma, Random Projection, Data-driven method.

cs.LG

On Geometry of Information Flow for Causal Inference

Causal inference is perhaps one of the most fundamental concepts in science, beginning originally from the works of some of the ancient philosophers, through today, but also weaved strongly in current work from statisticians, machine learning experts, and scientists from many other fields. This paper takes the perspective of information flow, which includes the Nobel prize winning work on Granger-causality, and the recently highly popular transfer entropy, these being probabilistic in nature. Our main contribution will be to develop analysis tools that will allow a geometric interpretation of information flow as a causal inference indicated by positive transfer entropy. We will describe the effective dimensionality of an underlying manifold as projected into the outcome space that summarizes information flow. Therefore contrasting the probabilistic and geometric perspectives, we will introduce a new measure of causal inference based on the fractal correlation dimension conditionally applied to competing explanations of future forecasts, which we will write $GeoC_{y\rightarrow x}$. This avoids some of the boundedness issues that we show exist for the transfer entropy, $T_{y\rightarrow x}$. We will highlight our discussions with data developed from synthetic models of successively more complex nature: then include the Hénon map example, and finally a real physiological example relating breathing and heart rate function. Keywords: Causal Inference; Transfer Entropy; Differential Entropy; Correlation Dimension; Pinsker's Inequality; Frobenius-Perron operator.

cs.IT