Metabolic modeling and
networks in Glasgow
Rainer Breitling
Metabolomics has a privileged position in SysBiol
Dettmer et al. Mass Spectrom. Rev. 2007
Breitling et al. Nature Reviews Microbiology
2008
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Metabolomics is applicable for various questions
Trypanosoma brucei
metabolic drug responses
Richard Scheltema, Mike Barrett, Marke
Girolami, Dave Watson, Fabien Jourdan,
Richard Burchmore, SysTryp, SilicoTryp
Streptomyces coelicolor
antibiotic discovery and synthetic biology
Elena Merlo, Eriko Takano, Tauqeer Alam,
Lubbert Dijkhuizen, Roel Vonk, Marcel de
Vries, Marnix Medema, SysMO-STREAM
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Metabolomics is applicable for various questions
Leishmania donovani
genetics of drug resistance
Richard Scheltema, Andris Jankevics,
Saskia Decuypere, Jean-Claude Dujardin,
Ruben t’Kindt, Hideo Imamura, Graham
Coombs, Dave Watson, GEMINI
Homo sapiens
adipocyte biomarkers for diabetes
Han Roelofsen, Roel Vonk, Bert Groen,
Martijn Dijkstra
Breitling Trends in Endocrinology
2009
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WET
Metabolomics poses many challenges
data collection
DRY
sample preparation
data extraction
deconvolution of data
analysis
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Masses can be assigned putative identities
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Metabolic neighbors provide network context
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Iterative analysis allows to reconstruct global
metabolic networks ab initio
Breitling et al.
Metabolomics
2006, 2:155
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PeakML – core library
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Fully documented, well-defined, and platform-independent open source mass spectrometry specific API, complete with
programming examples.
Supports the major file formats PeakML, mzData, mzXML, mzML. Additionally offers a 1-to-1 mapping to the Thermo Raw
and Waters Raw file libraries.
Integrated chemistry (e.g. molecular formulae, mass conversion, periodic table), math (e.g. statistics, wavelet transform,
function fitting, and loess and Savitzky-Golay), and visualization (JFreeChart and SWT for user interface applications)
routines.
Efficient memory usage.
Scheltema et al. Analytical Chem. 2011
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PeakML – core library
The API is fully documented;
accessible through javadoc
generated HTML pages
Extensive, step-by-step
programming examples provided
for first-time users
Scheltema et al. Analytical Chem. 2011
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PeakML Viewer – UI support
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Rapid visualization of
PeakML files.
Offers intuitive support for
sorting and filtering data.
Visualizes results in system
annotations (derivatives:
relation.id, relation.ship;
identifications: identification).
Rapid inspection of data
quality and offers the
potential to grab peaks of
interest and store these in a
separate file.
Dataset comparison options.
Exports graphs to PDF-files.
Scheltema et al. Analytical Chem. 2011
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mzMatch – reference pipeline
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A set of agile command-line tools
Fully documented command-line parameters, complete with examples
Supports: signal extraction, signal matching, signal alignment, noise filtering (blank
removal, coda-dw, rsd-filter), derivative detection, normalization (z-score, quantile,
van den Sompele), recovery and database matching (cyc-db’s, lipidmaps, kegg,
hmdb, ESI contaminants)
Scheltema et al. Analytical Chem. 2011
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MetSamp Bayesian peak disambiguation
Rogers et al. Bioinformatis 2009
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MetSamp Bayesian peak disambiguation
Rogers et al. Bioinformatis 2009
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Trypanosoma brucei
Successful mechanistic
prediction based on mathematical
modeling and verified by
experimentation
Bakker et al. J. Biol. Chem. 1997;
Haanstra et al. PNAS 2008
Modeling challenges
quantitative  semi-quantitative  stoichiometric  topological
Estimating posterior distribution
of parameters by MCMC
In Systems Biology, likelihood functions are
highly non-convex (multi-modal posteriors)
Systematic documentation of uncertainty
Acknowledgements
University of Glasgow
Andris Jankevics, Fiona Achcar, Mike Barrett, David
Wildridge, Isabel Vincent, Charles Ebikeme, Richard
Burchmore, Simon Rogers
University of Groningen, The Netherlands
Richard Scheltema, Eriko Takano, Elena Merlo, Lubbert
Dijkhuizen, Tauqeer Alam, Ritsert Jansen
University Medical Center Groningen
Marcel de Vries, Han Roelofsen, Roel Vonk
Institute of Tropical Medicine, Antwerp
Jean-Claude Dujardin, Saskia Decuypere, Ruben t’Kindt
Sanger Institute, Cambridge
Matt Berriman, Christiane Hertz-Fowler, Hideo Imamura
Wageningen University
Joost Keurentjes, Ric de Vos, Dick Vreugdenhil, Twan
America, Maarten Koornneef
University of Strathclyde
Graham Coombs, Dave Watson, Anas Kamleh
Phenomenome Discoveries Inc., Canada
Dayan Goodenowe
Norwegian University of Science and Technology
Per Bruheim, Alexander Wentzel, Trond Ellingsen
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