PMG: Multi-core Metabolite Identification

Jaghoori, Mohammad Mahdi; Jongmans, Sung-Shik; Boer, Frank de; Peironcely, Julio E.; Faulon, Jean-Loup; Reijmers, Theo H.; Hankemeier, Thomas

doi:10.1016/j.entcs.2013.11.005

Cited by 9 publications

(14 citation statements)

References 3 publications

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“…Our intent here is not to provide the fastest enumeration algorithm but to demonstrate how RetroPath2.0 can perform that job once appropriate reaction rules are provided. However, we provide in Additional file 2 : Figure S1 a comparison of Retropath2.0’s execution time with the OMG and PMG software tools [ 25 , 26 ] specifically dedicated to isomers enumeration. Retropath2.0 is found faster than OMG but slower than PMG.…”

Section: Resultsmentioning

confidence: 99%

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

Koch¹,

Duigou²,

Carbonell³

et al. 2017

J Cheminform

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Background: Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for. Results:Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME Analytics Platform. Conclusion:We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

Koch¹,

Duigou²,

Carbonell³

et al. 2017

J Cheminform

Self Cite

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show abstract

“…For the purposes of this study, during this step the actual unknown and all of its stereoisomers are deleted in order to simulate the unavailability of the unknown in the PubChem database. Combinatorial structure generation with Parallel Molecular Generator (PMG) [ 26 ]; structure generation is controlled by the seed structure and a list of non-endogenous mammalian structures ( i.e. , structures not allowed in the PMG generated structures).…”

Section: Methodsmentioning

confidence: 99%

“…Combinatorial structure generation with Parallel Molecular Generator (PMG) [ 26 ]; structure generation is controlled by the seed structure and a list of non-endogenous mammalian structures ( i.e. , structures not allowed in the PMG generated structures).…”

Section: Methodsmentioning

confidence: 99%

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Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics

et al. 2016

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Metabolite structure identification remains a significant challenge in nontargeted metabolomics research. One commonly used strategy relies on searching biochemical databases using exact mass. However, this approach fails when the database does not contain the unknown metabolite (i.e., for unknown-unknowns). For these cases, constrained structure generation with combinatorial structure generators provides a potential option. Here we evaluated structure generation constraints based on the specification of: (1) substructures required (i.e., seed structures); (2) substructures not allowed; and (3) filters to remove incorrect structures. Our approach (database assisted structure identification, DASI) used predictive models in MolFind to find candidate structures with chemical and physical properties similar to the unknown. These candidates were then used for seed structure generation using eight different structure generation algorithms. One algorithm was able to generate correct seed structures for 21/39 test compounds. Eleven of these seed structures were large enough to constrain the combinatorial structure generator to fewer than 100,000 structures. In 35/39 cases, at least one algorithm was able to generate a correct seed structure. The DASI method has several limitations and will require further experimental validation and optimization. At present, it seems most useful for identifying the structure of unknown-unknowns with molecular weights <200 Da.

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“…Our intent here is not to provide the fastest enumeration algorithm but to demonstrate how RetroPath2.0 can perform that job once appropriate reaction rules are provided. However, we provide in supplementary Figure S1 a comparison of Retropath2.0's execution time with the OMG and PMG software tools [25,26] specifically dedicated to isomers enumeration. Retropath2.0 is found faster than OMG but slower than PMG.…”

Section: Isomer Enumerationmentioning

confidence: 99%

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

Koch

Duigou

Carbonell

et al. 2017

Preprint

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Background: Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for. Results:Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure 1 . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/158147 doi: bioRxiv preprint first posted online biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME analytics platform. Conclusion:We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including, molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.

show abstract

PMG: Multi-core Metabolite Identification

Cited by 9 publications

References 3 publications

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

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