Integrating experimental knowledge Michael Witting, Research Unit - PowerPoint PPT Presentation

Integrating experimental knowledge Michael Witting, Research Unit Analytical BioGeoChemistry, HMGU Dagstuhl Seminar “Computational Metabolomics” 1.12.2015

Experimental Knowledge Know your toolbox! • Know your system! • Know your organism! • (or at least ask your analytical chemist of choice …)

Experimental Knowledge A lot of effort is made to analyze MS, MS2, MS3 spectra, but… • Separation dimension or other orthogonal methods are often neglected • Liquid Chromatography (LC) • Incl. 2D-LC • Gas Chromatography (GC) • Incl. 2D-GC • Capillary Electrophoresis (CE) • Supercritical Fluid Chromatography (SFC) • Ion Mobility Spectrometry (IMS) • Traveling wave • That information has to be also stored FAIMS • somewhere!!! Drift tube • (CV for that!!!)

Retention time indexing in (RP-)LC-MS Michael Quilliam, personal communication

Retention time indexing in (RP-)LC-MS A New Retention Index System for LC-MS, HPLC 2015, Geneva

Retention time indexing in (RP-)LC-MS neat Spiked to matrix

Retention time indexing in (RP-)LC-MS Evaluation of different matrices • Plants • Plasma • Urine • C. elegans extracts • Bacterial extracts • Feces • Liver extracts • Evaluation of different gradients • Evaluation of different column • dimensions Different chemistries and • projection between different systems Ring-trial recently started •

Retention projection/prediction Jan Stanstrup, Steffen Neumann, and Urška Vrhovšek PredRet: Prediction of Retention Time by Direct Mapping between Multiple Chromatographic Systems Anal. Chem., 2015, 87 (18), pp 9421 – 9428

Retention time prediction in metabolomics

Data set overview Creek et al. • ZIC-HILIC • 120 standards • MLR on 6 descriptors, 35% CV • Eugster et al. • BEH C18 • 260 standards • PLS, ANN on 8 descriptors, 2.5 minutes 30 min gradient CV • Cao et al. • ZIC-pHILIC • 93 standards • RF, MLR on 11 descriptors, 5.1% error no CV, 9.4% CV •

Creek et al. Darren J. Creek, Andris Jankevics, Rainer Breitling, David G. Watson, Michael P. Barrett, and Karl E. V. Burgess Toward Global Metabolomics Analysis with Hydrophilic Interaction Liquid ChromatographyMass Spectrometry: Improved Metabolite Identification by Retention Time Prediction Anal Chem. 2011 Nov 15;83(22):8703-10. doi: 10.1021/ac2021823. Epub 2011 Oct 21.

Eugster et al. Philippe J. Eugster, Julien Boccard, Benjamin Debrus, Lise Bréant, Jean-Luc Wolfender, Sophie Martel, Pierre-Alain Carrupt Retention time prediction for dereplication of natural products (CxHyOz) in LC – MS metabolite profiling Phytochemistry. 2014 Dec;108:196-207

Cao et al. C 5 H 11 NO 3 S Mingshu Cao, Karl Fraser, Jan Huege, Tom Featonby, Susanne Rasmussen, Chris Jones Predicting retention time in hydrophilic interaction liquid chromatography mass spectrometry and its use for peak annotation in metabolomics Metabolomics. 2015;11(3):696-706. Epub 2014 Sep 7.

SM(t40:1)/PE-Cer(t43:1) [M+H]+ PC(37:1) [M+H]+ HexCer(d40:3) [M+Na]+

EIC: (38,39-42,09 ms) - Cbr_JU1018_001.d EIC: (29,80-35,25 ms) - Cbr_JU1018_001.d EIC: (42,49-48,33 ms) - Cbr_JU1018_001.d