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Kevin B. Flores

Publications and source records attributed to Kevin B. Flores.

7 recordsLinked to original sources

Observable-Reduction-Guided Sparse Regression for Partially Observed Active-Quiescent Systems

Active-quiescent switching occurs in biological populations in which growth is confined to a proliferative active state, while cells may reversibly enter a nonproliferative quiescent state. Experiments often observe only part of this process, through active-state markers, aggregate population measurements, or aggregate data supplemented by sparse active-state observations. Such measurements arise when marker panels are limited, active-state assays require fixation or endpoint sampling, or only total cell number, optical density, tumor burden, or aggregate fluorescence is reported. These observation choices complicate sparse regression methods such as sparse identification of nonlinear dynamics (SINDy), because the measured variable may satisfy a different equation from the underlying active-quiescent system. A library chosen for the wrong observable may therefore fit a trajectory without preserving mechanistic interpretation or transferability. We study this issue using a two-compartment ordinary differential equation model. We define observable reduction as the elimination of hidden states to obtain the differential equation satisfied by the measured variable. For several biologically relevant growth laws, we derive observation-specific reductions and use them to construct sparse-regression libraries. Using synthetic data, we compare these structured libraries with standard polynomial SINDy. Polynomial libraries can match training trajectories while failing coefficient-relation and transfer tests, whereas reduction-guided libraries recover interpretable coefficient maps when the observed regime is informative. These results show that interpretable equation learning in hidden-compartment systems requires matching both the regression target and candidate library to the observation process.

math.DS

Enhancing generalizability of model discovery across parameter space with multi-experiment equation learning (ME-EQL)

Agent-based modeling (ABM) is a powerful tool for understanding self-organizing biological systems, but it is computationally intensive and often not analytically tractable. Equation learning (EQL) methods can derive continuum models from ABM data, but they typically require extensive simulations for each parameter set, raising concerns about generalizability. In this work, we extend EQL to Multi-experiment equation learning (ME-EQL) by introducing two methods: one-at-a-time ME-EQL (OAT ME-EQL), which learns individual models for each parameter set and connects them via interpolation, and embedded structure ME-EQL (ES ME-EQL), which builds a unified model library across parameters. We demonstrate these methods using a birth--death mean-field model and an on-lattice agent-based model of birth, death, and migration with spatial structure. Our results show that both methods significantly reduce the relative error in recovering parameters from agent-based simulations, with OAT ME-EQL offering better generalizability across parameter space. Our findings highlight the potential of equation learning from multiple experiments to enhance the generalizability and interpretability of learned models for complex biological systems.

cs.LG

Learning differential equation models from stochastic agent-based model simulations

Agent-based models provide a flexible framework that is frequently used for modelling many biological systems, including cell migration, molecular dynamics, ecology, and epidemiology. Analysis of the model dynamics can be challenging due to their inherent stochasticity and heavy computational requirements. Common approaches to the analysis of agent-based models include extensive Monte Carlo simulation of the model or the derivation of coarse-grained differential equation models to predict the expected or averaged output from the agent-based model. Both of these approaches have limitations, however, as extensive computation of complex agent-based models may be infeasible, and coarse-grained differential equation models can fail to accurately describe model dynamics in certain parameter regimes. We propose that methods from the equation learning field provide a promising, novel, and unifying approach for agent-based model analysis. Equation learning is a recent field of research from data science that aims to infer differential equation models directly from data. We use this tutorial to review how methods from equation learning can be used to learn differential equation models from agent-based model simulations. We demonstrate that this framework is easy to use, requires few model simulations, and accurately predicts model dynamics in parameter regions where coarse-grained differential equation models fail to do so. We highlight these advantages through several case studies involving two agent-based models that are broadly applicable to biological phenomena: a birth-death-migration model commonly used to explore cell biology experiments and a susceptible-infected-recovered model of infectious disease spread.

math.DS

Topological data analysis distinguishes parameter regimes in the Anderson-Chaplain model of angiogenesis

Angiogenesis is the process by which blood vessels form from pre-existing vessels. It plays a key role in many biological processes, including embryonic development and wound healing, and contributes to many diseases including cancer and rheumatoid arthritis. The structure of the resulting vessel networks determines their ability to deliver nutrients and remove waste products from biological tissues. Here we simulate the Anderson-Chaplain model of angiogenesis at different parameter values and quantify the vessel architectures of the resulting synthetic data. Specifically, we propose a topological data analysis (TDA) pipeline for systematic analysis of the model. TDA is a vibrant and relatively new field of computational mathematics for studying the shape of data. We compute topological and standard descriptors of model simulations generated by different parameter values. We show that TDA of model simulation data stratifies parameter space into regions with similar vessel morphology. The methodologies proposed here are widely applicable to other synthetic and experimental data including wound healing, development, and plant biology.

q-bio.QM

Biologically-informed neural networks guide mechanistic modeling from sparse experimental data

Biologically-informed neural networks (BINNs), an extension of physics-informed neural networks [1], are introduced and used to discover the underlying dynamics of biological systems from sparse experimental data. In the present work, BINNs are trained in a supervised learning framework to approximate in vitro cell biology assay experiments while respecting a generalized form of the governing reaction-diffusion partial differential equation (PDE). By allowing the diffusion and reaction terms to be multilayer perceptrons (MLPs), the nonlinear forms of these terms can be learned while simultaneously converging to the solution of the governing PDE. Further, the trained MLPs are used to guide the selection of biologically interpretable mechanistic forms of the PDE terms which provides new insights into the biological and physical mechanisms that govern the dynamics of the observed system. The method is evaluated on sparse real-world data from wound healing assays with varying initial cell densities [2].

q-bio.QM

Learning Equations from Biological Data with Limited Time Samples

Equation learning methods present a promising tool to aid scientists in the modeling process for biological data. Previous equation learning studies have demonstrated that these methods can infer models from rich datasets, however, the performance of these methods in the presence of common challenges from biological data has not been thoroughly explored. We present an equation learning methodology comprised of data denoising, equation learning, model selection and post-processing steps that infers a dynamical systems model from noisy spatiotemporal data. The performance of this methodology is thoroughly investigated in the face of several common challenges presented by biological data, namely, sparse data sampling, large noise levels, and heterogeneity between datasets. We find that this methodology can accurately infer the correct underlying equation and predict unobserved system dynamics from a small number of time samples when the data is sampled over a time interval exhibiting both linear and nonlinear dynamics. Our findings suggest that equation learning methods can be used for model discovery and selection in many areas of biology when an informative dataset is used. We focus on glioblastoma multiforme modeling as a case study in this work to highlight how these results are informative for data-driven modeling-based tumor invasion predictions.

q-bio.QM

Learning partial differential equations for biological transport models from noisy spatiotemporal data

We investigate methods for learning partial differential equation (PDE) models from spatiotemporal data under biologically realistic levels and forms of noise. Recent progress in learning PDEs from data have used sparse regression to select candidate terms from a denoised set of data, including approximated partial derivatives. We analyze the performance in utilizing previous methods to denoise data for the task of discovering the governing system of partial differential equations (PDEs). We also develop a novel methodology that uses artificial neural networks (ANNs) to denoise data and approximate partial derivatives. We test the methodology on three PDE models for biological transport, i.e., the advection-diffusion, classical Fisher-KPP, and nonlinear Fisher-KPP equations. We show that the ANN methodology outperforms previous denoising methods, including finite differences and polynomial regression splines, in the ability to accurately approximate partial derivatives and learn the correct PDE model.

math.DS