Comparative evaluation of atom mapping algorithms for balanced metabolic reactions: application to Recon 3D

Gonzalez, Germán Andrés; Assal, Lemmer R. P. El; Noronha, Alberto; Thiele, Ines; Haraldsdóttir, Hulda S.; Fleming, Ronan M. T.

doi:10.1186/s13321-017-0223-1

Cited by 37 publications

(43 citation statements)

References 35 publications

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“…We obtained high-quality structural coverage for over 80% of the human metabolic proteome ( Figure 2(a) ; Supplementary Figure 6 ; Supplementary Tables 2–4 ) and 85% of the metabolome ( Figure 2(b) ). Furthermore, we used 2,369 unique metabolite structures to trace algorithmically atom transitions 28 (from each substrate to product atom) for 7,804 (87%) internal, mass-balanced reactions of the Recon 3D derived model (Online Methods; Supplementary Note 3 ) . The prediction accuracy of the algorithms was validated by comparison with 512 manually curated atom mapped reactions ( Figure 2(c) ; Supplementary Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

Recon3D enables a three-dimensional view of gene variation in human metabolism

et al. 2018

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Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures. These data provide a unique resource for investigating molecular mechanisms of human metabolism. Recon3D is available at http://vmh.life.

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Section: Resultsmentioning

confidence: 99%

Recon3D enables a three-dimensional view of gene variation in human metabolism

et al. 2018

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“…The data were analyzed by a new method that naturally split each reaction into compound pairs and loner compounds, which we called architectures (Vazquez-Hernandez et al in BMC Syst Biol 12:63, 2018). The data include a set of 7491 curated reactions from the KEGG-Ligand data set.…”

Section: Data Descriptionmentioning

confidence: 99%

“…Genome-scale metabolic reconstruction requires that information about chemical transformations be known, and atom mappers are convenient methods for providing a one-to-one comparison of an atom in a substrate and an atom in a product [1, 2]. Atom mappers use heuristic approximations to rapidly identify common substructures between two compounds on the basis of a graph comparison method [2–4], information on the chemical environment and the removal of noninformative atoms.…”

Section: Objectivementioning

confidence: 99%

“…As a result, atom mappers can give optimal and suboptimal solutions that must be manually confirmed to ensure their accuracy. Most importantly, previous work related to atom mappers has focused on how to efficiently compute metrics for chemical structures, but the accuracy of these methods has not been assessed for large networks [1, 3]. This last point is an important issue because methods devoted to pathway discovery have used the results of atom mapping and reactant pairings as input to define new pathways.…”

Section: Objectivementioning

confidence: 99%

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Reactant pairs and reaction organization patterns produced by a new rule-based approach

Vazquez-Hernandez¹,

Loza²,

Gutiérrez-Ríos³

2018

BMC Res Notes

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ObjectivesImprovements in bioinformatics applications for the enzyme identification of biochemical reactions, enzyme classifications, mining for specific inhibitors and pathfinding require the accurate computational detection of reaction similarity. We provide a set of substrate-product pairs, clustered by reactions that share similar chemical transformation patterns, for which accuracy was calculated, comparing this set with manually curated data sets.Data descriptionThe data were analyzed by a new method that naturally split each reaction into compound pairs and loner compounds, which we called architectures (Vazquez-Hernandez et al. in BMC Syst Biol 12:63, 2018). The data include a set of 7491 curated reactions from the KEGG-Ligand data set. The data are presented in two formats, a string format and a tree structure, both of which reflect the splitting process and the final architectures of each reaction. We are also reporting sets of reactions that show similar splitting patterns naturally grouped into clusters of tree structures. The compound pairs in each cluster were compared with the reactant pairs proposed by the KEGG-RCLASS data set, and a match precision value is also provided. These data were collected with the aim of providing research with a confident set of reactant pairs that is useful for selecting between alternative substrate-product pairs predicted by pathfinders.

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“…It is not yet possible to fully automate the atom numbering during metabolic reaction. Note that the five main existing solutions have a success rate of 91% compared with manual mapping, which means that errors would remain with such an approach[71]. We have thus proposed a graphical output in order to facilitate the check of encoded molecule structures (S5-S6 Figs).The Pathmodel tool was developed to support reasoning based on the metabolic pathway drift hypothesis in order to automatically infer new reactions and metabolites.…”

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Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift

Belcour

Girard

Aïte

et al. 2018

Preprint

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Inferring genome-scale metabolic networks in emerging model organisms is challenging because of incomplete biochemical knowledge and incomplete conservation of biochemical pathways during evolution. This limits the possibility to automatically transfer knowledge from well-established model organisms. Therefore, specific bioinformatic tools are necessary to infer new biochemical reactions and new metabolic structures that can be checked experimentally. Using an integrative approach combining both genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterol or mycosporine-like amino acids (MAA) synthesis pathways, undergo substantial turnover. This phenomenon, which we formally define as "metabolic pathway drift", is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a new methodological approach to formalize the logical reasoning necessary to infer new reactions and new molecular structures, based on previous biochemical knowledge. We use this approach to infer previously unknown reactions in the sterol and MAA pathways. Author summaryGenome-scale metabolic models describe our current understanding of all metabolic pathways occuring in a given organism. For emerging model species, where few biochemical data are available about really occurring enzymatic activities, such metabolic models are mainly based on transferring knowledge from other more studied species, based on the assumption that the same genes have the same function in the compared species. However, integration of metabolomic data into genome-scale metabolic models leads to situations where gaps in pathways cannot be filled by known enzymatic reactions from existing databases. This is due to structural variation in metabolic pathways accross evolutionary time. In such cases, it is necessary to use complementary approaches to infer new reactions and new metabolic intermediates using logical reasoning, based on available partial biochemical knowledge.Here we present a proof of concept that this is feasible and leads to hypotheses that are precise enough to be a starting point for new experimental work. the well-studied human pathogenic bacterium Mycobacterium tuberculosis, high throughput metabolomic screens revealed an unexpected diversity of reactions in central carbon metabolism [9]. Evolutionary models have already been developed to explain the arising of new pathways, with most experimental validations being focused so far at the level of individual enzyme activities [10]. The complementary question, how much conserved corresponding to Z-palythenic acid in C. crispus extracts, which does not support dehydration occuring before decarboxylation, as proposed in other species (Fig 4 and [65]). The structure of a new intermediate was therefore inferred manually, leading to MAA2 on Figure 8.Calculating its m/z ratio,...

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Comparative evaluation of atom mapping algorithms for balanced metabolic reactions: application to Recon 3D

Cited by 37 publications

References 35 publications

Recon3D enables a three-dimensional view of gene variation in human metabolism

Recon3D enables a three-dimensional view of gene variation in human metabolism

Reactant pairs and reaction organization patterns produced by a new rule-based approach

Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift

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