scholarly journals A semantics, energy-based approach to automate biomodel composition

2021 ◽  
Author(s):  
Niloofar Shahidi ◽  
Michael Pan ◽  
Kenneth Tran ◽  
Edmund Crampin ◽  
David Phillip Nickerson

Hierarchical modelling is essential to achieving complex, large-scale models. However, not all modelling schemes support hierarchical composition, and correctly mapping points of connection between models requires comprehensive knowledge of each model's components and assumptions. To address these challenges in integrating biosimulation models, we propose an approach to automatically and confidently compose biosimulation models. The approach uses bond graphs to combine aspects of physical and thermodynamics-based modelling with biological semantics. We improved on existing approaches by using semantic annotations to automate the recognition of common components. The approach is illustrated by coupling a model of the Ras-MAPK cascade to a model of the upstream activation of EGFR. Through this methodology, we aim to assist researchers and modellers in readily having access to more comprehensive biological systems models.

2021 ◽  
Author(s):  
Michael Pan ◽  
Peter J. Gawthrop ◽  
Joseph Cursons ◽  
Edmund Crampin

It is widely acknowledged that the construction of large-scale dynamic models in systems biology requires complex modelling problems to be broken up into more manageable pieces. To this end, both modelling and software frameworks are required to enable modular modelling. While there has been consistent progress in the development of software tools to enhance model reusability, there has been a relative lack of consideration for how underlying biophysical principles can be applied to this space. Bond graphs combine the aspects of both modularity and physics-based modelling. In this paper, we argue that bond graphs are compatible with recent developments in modularity and abstraction in systems biology, and are thus a desirable framework for constructing large-scale models. We use two examples to illustrate the utility of bond graphs in this context: a model of a mitogen-activated protein kinase (MAPK) cascade to illustrate the reusability of modules and a model of glycolysis to illustrate the ability to modify the model granularity.


2021 ◽  
Vol 17 (10) ◽  
pp. e1009513
Author(s):  
Michael Pan ◽  
Peter J. Gawthrop ◽  
Joseph Cursons ◽  
Edmund J. Crampin

It is widely acknowledged that the construction of large-scale dynamic models in systems biology requires complex modelling problems to be broken up into more manageable pieces. To this end, both modelling and software frameworks are required to enable modular modelling. While there has been consistent progress in the development of software tools to enhance model reusability, there has been a relative lack of consideration for how underlying biophysical principles can be applied to this space. Bond graphs combine the aspects of both modularity and physics-based modelling. In this paper, we argue that bond graphs are compatible with recent developments in modularity and abstraction in systems biology, and are thus a desirable framework for constructing large-scale models. We use two examples to illustrate the utility of bond graphs in this context: a model of a mitogen-activated protein kinase (MAPK) cascade to illustrate the reusability of modules and a model of glycolysis to illustrate the ability to modify the model granularity.


Author(s):  
D. Keith Walters ◽  
Greg W. Burgreen ◽  
Robert L. Hester ◽  
David S. Thompson ◽  
David M. Lavallee ◽  
...  

Computational fluid dynamics (CFD) simulations were performed for unsteady periodic breathing conditions, using large-scale models of the human lung airway. The computational domain included fully coupled representations of the orotracheal region and large conducting zone up to generation four (G4) obtained from patient-specific CT data, and the small conducting zone (to G16) obtained from a stochastically generated airway tree with statistically realistic geometrical characteristics. A reduced-order geometry was used, in which several airway branches in each generation were truncated, and only select flow paths were retained to G16. The inlet and outlet flow boundaries corresponded to the oronasal opening (superior), the inlet/outlet planes in terminal bronchioles (distal), and the unresolved airway boundaries arising from the truncation procedure (intermediate). The cyclic flow was specified according to the predicted ventilation patterns for a healthy adult male at three different activity levels, supplied by the whole-body modeling software HumMod. The CFD simulations were performed using Ansys FLUENT. The mass flow distribution at the distal boundaries was prescribed using a previously documented methodology, in which the percentage of the total flow for each boundary was first determined from a steady-state simulation with an applied flow rate equal to the average during the inhalation phase of the breathing cycle. The distal pressure boundary conditions for the steady-state simulation were set using a stochastic coupling procedure to ensure physiologically realistic flow conditions. The results show that: 1) physiologically realistic flow is obtained in the model, in terms of cyclic mass conservation and approximately uniform pressure distribution in the distal airways; 2) the predicted alveolar pressure is in good agreement with previously documented values; and 3) the use of reduced-order geometry modeling allows accurate and efficient simulation of large-scale breathing lung flow, provided care is taken to use a physiologically realistic geometry and to properly address the unsteady boundary conditions.


2017 ◽  
Vol 50 (1) ◽  
pp. 3287-3293 ◽  
Author(s):  
Erik Frisk ◽  
Mattias Krysander ◽  
Daniel Jung

Author(s):  
Alessandro Achille ◽  
Giovanni Paolini ◽  
Glen Mbeng ◽  
Stefano Soatto

Abstract We introduce an asymmetric distance in the space of learning tasks and a framework to compute their complexity. These concepts are foundational for the practice of transfer learning, whereby a parametric model is pre-trained for a task, and then fine tuned for another. The framework we develop is non-asymptotic, captures the finite nature of the training dataset and allows distinguishing learning from memorization. It encompasses, as special cases, classical notions from Kolmogorov complexity and Shannon and Fisher information. However, unlike some of those frameworks, it can be applied to large-scale models and real-world datasets. Our framework is the first to measure complexity in a way that accounts for the effect of the optimization scheme, which is critical in deep learning.


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