POSTER PRESENTATION Open Access Expanding and understanding metabolite space Julio E Peironcely 1* , Andreas Bender 2 , M Rojas-Chertó 2 , T Reijmers 2 , L Coulier 1 , T Hankemeier 2 From 5th German Conference on Cheminformatics: 23. CIC-Workshop Goslar, Germany. 8-10 November 2009 In metabolomics the identity and role of low mass molecules called metabolites that are produced in cell metabolic processes are investigated. These make them valuable indicators of the phenotype of a biological sys- tem. The ‘ Metabolite Space’ is the total chemical universe of metabolites present in all compartments and in all states from any organism. These molecules exhibit common features that form what can be called ‘metabolite likeness’. Here, we focus on the human metabolite space, including both endogenous and exogenous (such as drug) metabolites. In order to analyze the ‘Metabolite Space’, we collected data from the Human Metabolome Database (HMDB) [1] which is a comprehensive database for human metabolites containing over 7000 compounds that were identified in several human biofluids and tissues. As there still remain many compounds to be identified that lay outside the boundaries of this known space, exploring this unknown region is crucial to evaluate ‘metabolite likeness’. In order to expand ‘Metabolite Space’ in our approach we employed the Retrosynthetic Combinatorial Analysis Procedure (RECAP) [2] to generate new molecules that possess features similar to those present in metabolites, however in other (but still likely) rearrangements. We studied how discernible these new molecules are from real metabolites and, hence, whether synthetic organic chemistry reactions are indeed able to expand the known universe of metabolites. We further studied the new chemistry present in the expanded metabolite space by looking at Murcko assemblies [3], ring systems and other chemical properties. The new metabolite space is compared to other small molecules, such as those obtained from the ZINC database, that are not metabolites. By combining all the above analyses we expect to characterize better the metabolite space, and further- more, to predict the metabolite-likeness of a molecule and to understand its immanent properties. Author details 1 TNO, Quality of Life, Utrechtseweg 48, Zeist, The Netherlands. 2 Netherlands Metabolomics Centre, University of Leiden, LACDR, Einsteinweg 55, 2333 CC Leiden, The Netherlands. Published: 4 May 2010 References 1. Wishart DS, et al: Nucleic Acids Res 2007, 35 Database: D521-526. 2. Lewell XQ, Judd DB, Watson SP, Hann MM: J Chem Inf Comput Sci 1998, 38:511-522. 3. Bemis GW, Murcko MA: J Med Chem 1996, 39:2887-2893. doi:10.1186/1758-2946-2-S1-P39 Cite this article as: Peironcely et al.: Expanding and understanding metabolite space. Journal of Cheminformatics 2010 2(Suppl 1):P39. Open access provides opportunities to our colleagues in other parts of the globe, by allowing anyone to view the content free of charge. Publish with ChemistryCentral and every scientist can read your work free of charge W. Jeffery Hurst, The Hershey Company. available free of charge to the entire scientific community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours you keep the copyright Submit your manuscript here: http://www.chemistrycentral.com/manuscript/ 1 TNO, Quality of Life, Utrechtseweg 48, Zeist, The Netherlands Peironcely et al. Journal of Cheminformatics 2010, 2(Suppl 1):P39 http://www.jcheminf.com/content/2/S1/P39 © 2010 Peironcely et al; licensee BioMed Central Ltd.

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Page 1: Expanding and understanding metabolite space

POSTER PRESENTATION Open Access

Expanding and understanding metabolite spaceJulio E Peironcely1*, Andreas Bender2, M Rojas-Chertó2, T Reijmers2, L Coulier1, T Hankemeier2

From 5th German Conference on Cheminformatics: 23. CIC-WorkshopGoslar, Germany. 8-10 November 2009

In metabolomics the identity and role of low massmolecules called metabolites that are produced in cellmetabolic processes are investigated. These make themvaluable indicators of the phenotype of a biological sys-tem. The ‘Metabolite Space’ is the total chemical uni-verse of metabolites present in all compartments and inall states from any organism. These molecules exhibitcommon features that form what can be called ‘metabo-lite likeness’. Here, we focus on the human metabolitespace, including both endogenous and exogenous (suchas drug) metabolites. In order to analyze the ‘MetaboliteSpace’, we collected data from the Human MetabolomeDatabase (HMDB) [1] which is a comprehensive data-base for human metabolites containing over 7000 com-pounds that were identified in several human biofluidsand tissues. As there still remain many compounds tobe identified that lay outside the boundaries of thisknown space, exploring this unknown region is crucialto evaluate ‘metabolite likeness’.In order to expand ‘Metabolite Space’ in our approach

we employed the Retrosynthetic Combinatorial AnalysisProcedure (RECAP) [2] to generate new molecules thatpossess features similar to those present in metabolites,however in other (but still likely) rearrangements. Westudied how discernible these new molecules are fromreal metabolites and, hence, whether synthetic organicchemistry reactions are indeed able to expand theknown universe of metabolites. We further studied thenew chemistry present in the expanded metabolite spaceby looking at Murcko assemblies [3], ring systems andother chemical properties. The new metabolite space iscompared to other small molecules, such as thoseobtained from the ZINC database, that are not metabo-lites. By combining all the above analyses we expect tocharacterize better the metabolite space, and further-more, to predict the metabolite-likeness of a moleculeand to understand its immanent properties.

Author details1TNO, Quality of Life, Utrechtseweg 48, Zeist, The Netherlands. 2NetherlandsMetabolomics Centre, University of Leiden, LACDR, Einsteinweg 55, 2333 CCLeiden, The Netherlands.

Published: 4 May 2010

References1. Wishart DS, et al: Nucleic Acids Res 2007, 35 Database: D521-526.2. Lewell XQ, Judd DB, Watson SP, Hann MM: J Chem Inf Comput Sci 1998,

38:511-522.3. Bemis GW, Murcko MA: J Med Chem 1996, 39:2887-2893.

doi:10.1186/1758-2946-2-S1-P39Cite this article as: Peironcely et al.: Expanding and understandingmetabolite space. Journal of Cheminformatics 2010 2(Suppl 1):P39.

Open access provides opportunities to our colleagues in other parts of the globe, by allowing

anyone to view the content free of charge.

Publish with ChemistryCentral and everyscientist can read your work free of charge

W. Jeffery Hurst, The Hershey Company.

available free of charge to the entire scientific communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Centralyours you keep the copyright

Submit your manuscript here:http://www.chemistrycentral.com/manuscript/

1TNO, Quality of Life, Utrechtseweg 48, Zeist, The Netherlands

Peironcely et al. Journal of Cheminformatics 2010, 2(Suppl 1):P39http://www.jcheminf.com/content/2/S1/P39