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A Graph-Based Framework for Multiscale Modeling of Physiological Transport

Trillions of chemical reactions occur in the human body every second, where the generated products are not only consumed locally but also transported to various locations in a systematic manner to sustain homeostasis. Current solutions to model these biological phenomena are restricted in computabil...

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Autores principales: Deepa Maheshvare, M., Raha, Soumyendu, Pal, Debnath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013063/
https://www.ncbi.nlm.nih.gov/pubmed/36925576
http://dx.doi.org/10.3389/fnetp.2021.802881
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author Deepa Maheshvare, M.
Raha, Soumyendu
Pal, Debnath
author_facet Deepa Maheshvare, M.
Raha, Soumyendu
Pal, Debnath
author_sort Deepa Maheshvare, M.
collection PubMed
description Trillions of chemical reactions occur in the human body every second, where the generated products are not only consumed locally but also transported to various locations in a systematic manner to sustain homeostasis. Current solutions to model these biological phenomena are restricted in computability and scalability due to the use of continuum approaches in which it is practically impossible to encapsulate the complexity of the physiological processes occurring at diverse scales. Here, we present a discrete modeling framework defined on an interacting graph that offers the flexibility to model multiscale systems by translating the physical space into a metamodel. We discretize the graph-based metamodel into functional units composed of well-mixed volumes with vascular and cellular subdomains; the operators defined over these volumes define the transport dynamics. We predict glucose drift governed by advective–dispersive transport in the vascular subdomains of an islet vasculature and cross-validate the flow and concentration fields with finite-element–based COMSOL simulations. Vascular and cellular subdomains are coupled to model the nutrient exchange occurring in response to the gradient arising out of reaction and perfusion dynamics. The application of our framework for modeling biologically relevant test systems shows how our approach can assimilate both multi-omics data from in vitro–in vivo studies and vascular topology from imaging studies for examining the structure–function relationship of complex vasculatures. The framework can advance simulation of whole-body networks at user-defined levels and is expected to find major use in personalized medicine and drug discovery.
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spelling pubmed-100130632023-03-15 A Graph-Based Framework for Multiscale Modeling of Physiological Transport Deepa Maheshvare, M. Raha, Soumyendu Pal, Debnath Front Netw Physiol Network Physiology Trillions of chemical reactions occur in the human body every second, where the generated products are not only consumed locally but also transported to various locations in a systematic manner to sustain homeostasis. Current solutions to model these biological phenomena are restricted in computability and scalability due to the use of continuum approaches in which it is practically impossible to encapsulate the complexity of the physiological processes occurring at diverse scales. Here, we present a discrete modeling framework defined on an interacting graph that offers the flexibility to model multiscale systems by translating the physical space into a metamodel. We discretize the graph-based metamodel into functional units composed of well-mixed volumes with vascular and cellular subdomains; the operators defined over these volumes define the transport dynamics. We predict glucose drift governed by advective–dispersive transport in the vascular subdomains of an islet vasculature and cross-validate the flow and concentration fields with finite-element–based COMSOL simulations. Vascular and cellular subdomains are coupled to model the nutrient exchange occurring in response to the gradient arising out of reaction and perfusion dynamics. The application of our framework for modeling biologically relevant test systems shows how our approach can assimilate both multi-omics data from in vitro–in vivo studies and vascular topology from imaging studies for examining the structure–function relationship of complex vasculatures. The framework can advance simulation of whole-body networks at user-defined levels and is expected to find major use in personalized medicine and drug discovery. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC10013063/ /pubmed/36925576 http://dx.doi.org/10.3389/fnetp.2021.802881 Text en Copyright © 2022 Deepa Maheshvare, Raha and Pal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Network Physiology
Deepa Maheshvare, M.
Raha, Soumyendu
Pal, Debnath
A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title_full A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title_fullStr A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title_full_unstemmed A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title_short A Graph-Based Framework for Multiscale Modeling of Physiological Transport
title_sort graph-based framework for multiscale modeling of physiological transport
topic Network Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013063/
https://www.ncbi.nlm.nih.gov/pubmed/36925576
http://dx.doi.org/10.3389/fnetp.2021.802881
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