scholarly journals ACBM: An Integrated Agent and Constraint Based Modeling Framework for Simulation of Microbial Communities

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emadoddin Karimian ◽  
Ehsan Motamedian
2018 ◽  
Vol 35 (13) ◽  
pp. 2332-2334 ◽  
Author(s):  
Federico Baldini ◽  
Almut Heinken ◽  
Laurent Heirendt ◽  
Stefania Magnusdottir ◽  
Ronan M T Fleming ◽  
...  

Abstract Motivation The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes. Results To address this gap, we created a comprehensive toolbox to model (i) microbe–microbe and host–microbe metabolic interactions, and (ii) microbial communities using microbial genome-scale metabolic reconstructions and metagenomic data. The Microbiome Modeling Toolbox extends the functionality of the constraint-based reconstruction and analysis toolbox. Availability and implementation The Microbiome Modeling Toolbox and the tutorials at https://git.io/microbiomeModelingToolbox.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Benjamín J. Sánchez ◽  
Feiran Li ◽  
Eduard J. Kerkhoven ◽  
Jens Nielsen

2019 ◽  
Author(s):  
Lin Liu ◽  
Alexander Bockmayr

AbstractIntegrated modeling of metabolism and gene regulation continues to be a major challenge in computational biology. While there exist approaches like regulatory flux balance analysis (rFBA), dynamic flux balance analysis (dFBA), resource balance analysis (RBA) or dynamic enzyme-cost flux balance analysis (deFBA) extending classical flux balance analysis (FBA) in various directions, there have been no constraint-based methods so far that allow predicting the dynamics of metabolism taking into account both macromolecule production costs and regulatory events.In this paper, we introduce a new constraint-based modeling framework named regulatory dynamic enzyme-cost flux balance analysis (r-deFBA), which unifies dynamic modeling of metabolism, cellular resource allocation and transcriptional regulation in a hybrid discrete-continuous setting.With r-deFBA, we can predict discrete regulatory states together with the continuous dynamics of reaction fluxes, external substrates, enzymes, and regulatory proteins needed to achieve a cellular objective such as maximizing biomass over a time interval. The dynamic optimization problem underlying r-deFBA can be reformulated as a mixed-integer linear optimization problem, for which there exist efficient solvers.


2018 ◽  
Vol 46 (2) ◽  
pp. 249-260 ◽  
Author(s):  
Martin H. Rau ◽  
Ahmad A. Zeidan

Genome-scale metabolic network reconstruction offers a means to leverage the value of the exponentially growing genomics data and integrate it with other biological knowledge in a structured format. Constraint-based modeling (CBM) enables both the qualitative and quantitative analyses of the reconstructed networks. The rapid advancements in these areas can benefit both the industrial production of microbial food cultures and their application in food processing. CBM provides several avenues for improving our mechanistic understanding of physiology and genotype–phenotype relationships. This is essential for the rational improvement of industrial strains, which can further be facilitated through various model-guided strain design approaches. CBM of microbial communities offers a valuable tool for the rational design of defined food cultures, where it can catalyze hypothesis generation and provide unintuitive rationales for the development of enhanced community phenotypes and, consequently, novel or improved food products. In the industrial-scale production of microorganisms for food cultures, CBM may enable a knowledge-driven bioprocess optimization by rationally identifying strategies for growth and stability improvement. Through these applications, we believe that CBM can become a powerful tool for guiding the areas of strain development, culture development and process optimization in the production of food cultures. Nevertheless, in order to make the correct choice of the modeling framework for a particular application and to interpret model predictions in a biologically meaningful manner, one should be aware of the current limitations of CBM.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren M. Lui ◽  
Erica L.-W. Majumder ◽  
Heidi J. Smith ◽  
Hans K. Carlson ◽  
Frederick von Netzer ◽  
...  

Over the last century, leaps in technology for imaging, sampling, detection, high-throughput sequencing, and -omics analyses have revolutionized microbial ecology to enable rapid acquisition of extensive datasets for microbial communities across the ever-increasing temporal and spatial scales. The present challenge is capitalizing on our enhanced abilities of observation and integrating diverse data types from different scales, resolutions, and disciplines to reach a causal and mechanistic understanding of how microbial communities transform and respond to perturbations in the environment. This type of causal and mechanistic understanding will make predictions of microbial community behavior more robust and actionable in addressing microbially mediated global problems. To discern drivers of microbial community assembly and function, we recognize the need for a conceptual, quantitative framework that connects measurements of genomic potential, the environment, and ecological and physical forces to rates of microbial growth at specific locations. We describe the Framework for Integrated, Conceptual, and Systematic Microbial Ecology (FICSME), an experimental design framework for conducting process-focused microbial ecology studies that incorporates biological, chemical, and physical drivers of a microbial system into a conceptual model. Through iterative cycles that advance our understanding of the coupling across scales and processes, we can reliably predict how perturbations to microbial systems impact ecosystem-scale processes or vice versa. We describe an approach and potential applications for using the FICSME to elucidate the mechanisms of globally important ecological and physical processes, toward attaining the goal of predicting the structure and function of microbial communities in chemically complex natural environments.


2018 ◽  
Author(s):  
Benjamín J. Sánchez ◽  
Feiran Li ◽  
Eduard J. Kerkhoven ◽  
Jens Nielsen

SummaryA recurrent problem in genome-scale metabolic models (GEMs) is to correctly represent lipids as biomass requirements, due to the numerous of possible combinations of individual lipid species and the corresponding lack of fully detailed data. In this study we present SLIMEr, a formalism for correctly representing lipid requirements in GEMs using commonly available experimental data. SLIMEr enhances a GEM with mathematical constructs where we Split Lipids Into Measurable Entities (SLIME reactions), in addition to constraints on both the lipid classes and the acyl chain distribution. By implementing SLIMEr on the consensus GEM of Saccharomyces cerevisiae, we can predict accurate amounts of lipid species, analyze the flexibility of the resulting distribution, and compute the energy costs of moving from one metabolic state to another. The approach shows potential for better understanding lipid metabolism in yeast under different conditions. SLIMEr is freely available at https://github.com/SysBioChalmers/SLIMEr.


2020 ◽  
Author(s):  
Teng Wang ◽  
Lingchong You

AbstractMobile genetic elements (MGEs), such as plasmids, phages, and transposons, play a critical role in mediating the transfer and maintenance of diverse traits and functions in microbial communities. This role depends on the ability of MGEs to persist. For a community consisting of multiple populations transferring multiple MGEs, however, the conditions underlying the persistence of these MGEs are poorly understood. Computationally, this difficulty arises from the combinatorial explosion associated with describing the gene flow in a complex community using the conventional modeling framework. Here, we describe an MGE-centric framework that makes it computationally feasible to analyze such transfer dynamics. Using this framework, we derive the persistence potential: a general, heuristic metric that predicts the persistence and abundance of any MGEs. We validate the metric with engineered microbial consortia transferring mobilizable plasmids and quantitative data available in the literature. Our modeling framework and the resulting metric have implications for developing a quantitative understanding of natural microbial communities and guiding the engineering of microbial consortia.


2018 ◽  
Author(s):  
Federico Baldini ◽  
Almut Heinken ◽  
Laurent Heirendt ◽  
Stefania Magnusdottir ◽  
Ronan M.T. Fleming ◽  
...  

MotivationThe application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes.ResultsTo address this shortage, we created a comprehensive toolbox to model i) microbe-microbe and host-microbe metabolic interactions, and ii) microbial communities using microbial genome-scale metabolic reconstructions and metagenomic data. The Microbiome Modeling Toolbox extends the functionality of the COBRA Toolbox.AvailabilityThe Microbiome Modeling Toolbox and the tutorials at https://git.io/microbiomeModelingToolbox.


Author(s):  
Devlin Moyer ◽  
Alan R. Pacheco ◽  
David B. Bernstein ◽  
Daniel Segrè

AbstractUncovering the general principles that govern the structure of metabolic networks is key to understanding the emergence and evolution of living systems. Artificial chemistries can help illuminate this problem by enabling the exploration of chemical reaction universes that are constrained by general mathematical rules. Here, we focus on artificial chemistries in which strings of characters represent simplified molecules, and string concatenation and splitting represent possible chemical reactions. We developed a novel Python package, ARtificial CHemistry NEtwork Toolbox (ARCHNET), to study string chemistries using tools from the field of stoichiometric constraint-based modeling. In addition to exploring the topological characteristics of different string chemistry networks, we developed a network-pruning algorithm that can generate minimal metabolic networks capable of producing a specified set of biomass precursors from a given assortment of environmental nutrients. We found that the composition of these minimal metabolic networks was influenced more strongly by the metabolites in the biomass reaction than the identities of the environmental nutrients. This finding has important implications for the reconstruction of organismal metabolic networks and could help us better understand the rise and evolution of biochemical organization. More generally, our work provides a bridge between artificial chemistries and stoichiometric modeling, which can help address a broad range of open questions, from the spontaneous emergence of an organized metabolism to the structure of microbial communities.


2020 ◽  
Author(s):  
Devlin Moyer ◽  
Alan R. Pacheco ◽  
David B. Bernstein ◽  
Daniel Segrè

AbstractUncovering the general principles that govern the architecture of metabolic networks is key to understanding the emergence and evolution of living systems. Artificial chemistries, in silico representations of chemical reaction networks arising from a defined set of mathematical rules, can help address this challenge by enabling the exploration of alternative chemical universes and the possible metabolic networks that could emerge within them. Here we focus on artificial chemistries in which strings of characters represent simplified molecules, and string concatenation and splitting represent possible chemical reactions. We study string chemistries using tools borrowed from the field of stoichiometric constraint-based modeling of organismal metabolic networks, through a novel Python package, ARtificial CHemistry NEtwork Toolbox (ARCHNET). In addition to exploring the complexity and connectivity properties of different string chemistries, we developed a network-pruning algorithm that can generate minimal metabolic networks capable of producing a specified set of biomass precursors from a given assortment of environmental molecules within the string chemistry framework. We found that the identities of the metabolites in the biomass reaction wield much more influence over the structure of the minimal metabolic networks than the identities of the nutrient metabolites — a notion that could help us better understand the rise and evolution of biochemical organization. Our work provides a bridge between artificial chemistries and stoichiometric modeling, which can help address a broad range of open questions, from the spontaneous emergence of an organized metabolism to the structure of microbial communities.


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