scholarly journals Software platforms to facilitate reconstructing genome-scale metabolic networks

2013 ◽  
Vol 16 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Joshua J. Hamilton ◽  
Jennifer L. Reed
2019 ◽  
Author(s):  
S. N. Mendoza ◽  
B. G Olivier ◽  
D Molenaar ◽  
B Teusink

AbstractSeveral genome-scale metabolic reconstruction software platforms have been developed and are being continuously updated. These tools have been widely applied to reconstruct metabolic models for hundreds of microorganisms ranging from important human pathogens to species of industrial relevance. However, these platforms, as yet, have not been systematically evaluated with respect to software quality, best potential uses and intrinsic capacity to generate high-quality, genome-scale metabolic models. It is therefore unclear for potential users which tool best fits the purpose of their research. In this work, we performed a systematic assessment of the current genome-scale reconstruction software platforms. To meet our goal, we first defined a list of features for assessing software quality related to genome-scale reconstruction, which we expect to be useful for the potential users of these tools. Subsequently, we used the feature list to evaluate the performance of each tool. In order to assess the similarity of the draft reconstructions to high-quality models, we compared each tool’s output networks with that of the high-quality, manually curated, models of Lactobacillus plantarum and Bordetella pertussis, representatives of gram-positive and gram-negative bacteria, respectively. We showed that none of the tools outperforms the others in all the defined features and that model builders should carefully choose a tool (or combinations of tools) depending on the intended use of the metabolic model.Author SummaryMetabolic networks that comprise biochemical reactions at genome-scale have become very useful to study and predict the phenotype of important microorganisms. Several software platforms exist to build these metabolic networks. Based on different approaches and utilizing a variety of databases it is, unfortunately, unclear what are the best scenarios to use each of these tools. Hence, to understand the potential uses of these tools, we created a list of relevant features for metabolic reconstruction and we evaluated the tools in all these categories. Here, we show that none of the tools is better than the other in all the evaluated categories; instead, each tool is more suitable for particular purposes. Therefore, users should carefully select the tool(s) that best fit the purpose of their research. This is the first time these tools are systematically evaluated and this overview can be used as a guide for selecting the correct tool(s) for each case.


FEBS Open Bio ◽  
2021 ◽  
Author(s):  
You‐Tyun Wang ◽  
Min‐Ru Lin ◽  
Wei‐Chen Chen ◽  
Wu‐Hsiung Wu ◽  
Feng‐Sheng Wang

2021 ◽  
Author(s):  
Ecehan Abdik ◽  
Tunahan Cakir

Genome-scale metabolic networks enable systemic investigation of metabolic alterations caused by diseases by providing interpretation of omics data. Although Mus musculus (mouse) is one of the most commonly used model...


2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Abdelhalim Larhlimi ◽  
Laszlo David ◽  
Joachim Selbig ◽  
Alexander Bockmayr

2010 ◽  
Vol 4 (1) ◽  
pp. 114 ◽  
Author(s):  
Karin Radrich ◽  
Yoshimasa Tsuruoka ◽  
Paul Dobson ◽  
Albert Gevorgyan ◽  
Neil Swainston ◽  
...  

2017 ◽  
Vol 9 (10) ◽  
pp. 830-835 ◽  
Author(s):  
Xingxing Jian ◽  
Ningchuan Li ◽  
Qian Chen ◽  
Qiang Hua

Reconstruction and application of genome-scale metabolic models (GEMs) have facilitated metabolic engineering by providing a platform on which systematic computational analysis of metabolic networks can be performed.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240953
Author(s):  
Christian Schulz ◽  
Eivind Almaas

Approaches for systematizing information of relatedness between organisms is important in biology. Phylogenetic analyses based on sets of highly conserved genes are currently the basis for the Tree of Life. Genome-scale metabolic reconstructions contain high-quality information regarding the metabolic capability of an organism and are typically restricted to metabolically active enzyme-encoding genes. While there are many tools available to generate draft reconstructions, expert-level knowledge is still required to generate and manually curate high-quality genome-scale metabolic models and to fill gaps in their reaction networks. Here, we use the tool AutoKEGGRec to construct 975 genome-scale metabolic draft reconstructions encoded in the KEGG database without further curation. The organisms are selected across all three domains, and their metabolic networks serve as basis for generating phylogenetic trees. We find that using all reactions encoded, these metabolism-based comparisons give rise to a phylogenetic tree with close similarity to the Tree of Life. While this tree is quite robust to reasonable levels of noise in the metabolic reaction content of an organism, we find a significant heterogeneity in how much noise an organism may tolerate before it is incorrectly placed in the tree. Furthermore, by using the protein sequences for particular metabolic functions and pathway sets, such as central carbon-, nitrogen-, and sulfur-metabolism, as basis for the organism comparisons, we generate highly specific phylogenetic trees. We believe the generation of phylogenetic trees based on metabolic reaction content, in particular when focused on specific functions and pathways, could aid the identification of functionally important metabolic enzymes and be of value for genome-scale metabolic modellers and enzyme-engineers.


2020 ◽  
Author(s):  
Tom J. Clement ◽  
Erik B. Baalhuis ◽  
Bas Teusink ◽  
Frank J. Bruggeman ◽  
Robert Planqué ◽  
...  

AbstractThe metabolic capabilities of cells determine their biotechnological potential, fitness in ecosystems, pathogenic threat levels, and function in multicellular organisms. Their comprehensive experimental characterisation is generally not feasible, particularly for unculturable organisms. In principle, the full range of metabolic capabilities can be computed from an organism’s annotated genome using metabolic network reconstruction. However, current computational methods cannot deal with genome-scale metabolic networks. Part of the problem is that these methods aim to enumerate all metabolic pathways, while computation of all (elementally balanced) conversions between nutrients and products would suffice. Indeed, the elementary conversion modes (ECMs, defined by Urbanczik and Wagner) capture the full metabolic capabilities of a network, but the use of ECMs has not been accessible, until now. We extend and explain the theory of ECMs, implement their enumeration in ecmtool, and illustrate their applicability. This work contributes to the elucidation of the full metabolic footprint of any cell.


2021 ◽  
Author(s):  
Christopher E. Lawson ◽  
Aniela B. Mundinger ◽  
Hanna Koch ◽  
Tyler B. Jacobson ◽  
Coty A. Weathersby ◽  
...  

AbstractNitrite-oxidizing bacteria belonging to the genus Nitrospira mediate a key step in nitrification and play important roles in the biogeochemical nitrogen cycle and wastewater treatment. While these organisms have recently been shown to exhibit metabolic flexibility beyond their chemolithoautotrophic lifestyle, including the use of simple organic compounds to fuel their energy metabolism, the metabolic networks controlling their autotrophic and mixotrophic growth remain poorly understood. Here, we reconstructed a genome-scale metabolic model for Nitrospira moscoviensis (iNmo686) and used constraint-based analysis to evaluate the metabolic networks controlling autotrophic and formatotrophic growth on nitrite and formate, respectively. Subsequently, proteomic analysis and 13C-tracer experiments with bicarbonate and formate coupled to metabolomic analysis were performed to experimentally validate model predictions. Our findings support that N. moscoviensis uses the reductive tricarboxylic acid cycle for CO2 fixation. We also show that N. moscoviensis can indirectly use formate as a carbon source by oxidizing it first to CO2 followed by reassimilation, rather than direct incorporation via the reductive glycine pathway. Our study offers the first measurements of Nitrospira’s in vivo central carbon metabolism and provides a quantitative tool that can be used for understanding and predicting their metabolic processes.ImportanceNitrospira are globally abundant nitrifying bacteria in soil and aquatic ecosystems and wastewater treatment plants, where they control the oxidation of nitrite to nitrate. Despite their critical contribution to nitrogen cycling across diverse environments, detailed understanding of their metabolic network and prediction of their function under different environmental conditions remains a major challenge. Here, we provide the first constraint-based metabolic model of N. moscoviensis representing the ubiquitous Nitrospira lineage II and subsequently validate this model using proteomics and 13C-tracers combined with intracellular metabolomic analysis. The resulting genome-scale model will serve as a knowledge base of Nitrospira metabolism and lays the foundation for quantitative systems biology studies of these globally important nitrite- oxidizing bacteria.


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