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METASPACE Theory

metaspace2020
November 11, 2018

METASPACE Theory

These slides are a part of the METASPACE training and present the bioinformatics for metabolite annotation of HR imaging MS used in METASPACE.

For more information on METASPACE, please visit the project website http://metaspace2020.eu, Twitter https://twitter.com/metaspace2020, or email us at [email protected].

metaspace2020

November 11, 2018
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  1. metabolite annotation engine HR imaging MS metabolite annotations metabolic images

    Tissue sections Other samples Metabolomics resources Imaging software repositories CLOUD technologies Open-source Metaspace http:|| METASPACE2020.eu @METASPACE2020 2015- 2017-
  2. m/z 718.54 m/z 204.12 Microbial interactions with Alex Koumoutsi, Nassos

    Typas (EMBL) 65 um pixel size C. albicans P. æruginosa Challenge: metabolite identification
  3. Challenge: metabolite identification Dark matter m/z A m/z B m/z

    C Glucose MW 180.063 [M+H]+=181.070 … in-source fragmentation ion adducts isotopologues dataset 100 GB / 100.000 spectra / 10.000.000 images Metabolome 100.000 molecules For 100K moleculaR structures
  4. Targeted metabolite imaging howto 1. Consider possible adducts – +H,

    +Na, +K or –H, –Cl 2. Calculate m/z of each adduct – principal or monoisotopic 3. Examine ion images 4. Examine the potential isotopic pattern 5. Estimate the ambiguity (any isomers? isobars?) 6. Validate with in situ MS/MS – On a region of high intensity
  5. Molecular annotation Fdr calculation 1. Consider possible adducts 2. Calculate

    m/z of each adduct 3. Examine images 4. Examine the potential isotopic pattern 5. Estimate the ambiguity (any isomers? isobars?) 1 3 4 3 2 5
  6. Spectral & spatial isotope scores 13 monoisotopic image structured? ok

    fine isotope structure matching theor? ok isotopic images co-localized? not è doesn‘t pass the filters
  7. Molecular annotation Fdr calculation Ok, all ions are scored by

    their likelihood ... But how to choose the cutoff?
  8. how to select parameters in proteomics Database Data Molecular Identification

    List of molecules Correct? 1. How to quantify correctness? 2. False Discovery Rate FDR = ratio of false positives 3. Don’t know false positives è cannot calculate FDR 4. Can we estimate it? true positives false positives
  9. How to estimate fdr In proteomics Database Data Molecular Identification

    Molecular IDs Fake database Molecular IDs “Decoy” “Target” FDR # false positives for target # identifications for target estimated FDR # target FPs # target IDs =  # decoy FPs # target IDs true positives false positives false positives positives: = = Target similar to Decoy similar defini3on =
  10. CLOUD SOLUTION: METASPACE Upload Metabolite images Finds molecules Metabolite imaging

    knowledge base http :// Metaspace2020 . eu Palmer et al, Nat Methods 2017 3000+ submissions 50+ labs Human, animal models, cancer cohorts All major tech represented
  11. Erlotinib Olanzapine 7-hydroxyolanzapine / 2-hydroxymethylolanzapine Swales et al. (2016) METASPACE

    reprocessing Not reported Olanzapine Swales et al. (2016) Sci Reports Data submitted by Nicole Strittmatter, Richard Goodwin (AstraZeneca) Cassette dosage Drug metabolite imaging
  12. METASPACE data contributors Alireza Abdolvahabi, Sarah Aboulmagd, Buck Achim, Rima

    Ait-Belkacem, Theodore Alexandrov, Christopher Anderton, Charlotte Bagger, Pierre Barbier Saint Hilaire, Michæl Becker, Janine Beckmann, Mikhail Belov, Dhaka Bhandari, Arunima Bhattacharjee, Tanja Bien, Mark Bokhart, Berin Boughton, John Bowling, Eike Brockmann, Achim Buck, Josephine Bunch, Christina Burr, Richard Caprioli, Claire Carter, Steve Castellino, Janfelt Christian, Dave Clarke, Katharina Clitherow, Julien Delecolle, Nicolas Desbenoit, Domenic Dreisbach, Klaus Dreisewerd, Maria Duenas, Livia Eberlin, Shane Ellis, Isabelle Fournier, Neha Garg, Vannur Garikapati, Kyana Garza, Mathieu Gaudin, Benedikt Geier, Erin Gemperline, Stefanie Gerbig, Cristina Gonzalez Lopez, Richard Goodwin, Christian Greunke, Gus Grey, Julian Griffin, Katharina Halbach, Zoe Hall, Anne Mette Handler, Mitsuhiro Hayashi, Ron Heeren, Bram Heijs, Dimitri Heintz, Corinna Henkel, Dirk Hoelscher, Carsten Hopf, Lennart Huizing, Aslihan Inal, Sophie Jacobsen, Christian Janfelt, Asta Maria Joensen, Emrys Jones, Patrik Kadesch, Maureen Kane, Pegah Khamehgir-Silz, Mario Kompauer, Vitaly Kovalev, Mélanie Lagarrigue, James Langridge, Sheerin Latham, Regis Lavigne, Oliver Lechtenfeld, Young Jin Lee, Lingjun Li, Maunel Liebeke, Michæl Linscheid, Logan Mackay, Liebeke Manuel, James McKenzie, Mira Merdas, Joris Meurs, Hidenobu Miyazawa, Astrid Moerman, David Muddiman, Max Müller, Konstantin Nagornov, Don Nguyen, Marty Paine, Andrew Palmer, József Pánczél, Heath Patterson, Robin Philip, Charles Pineau, Adam Pruska, Jusal Quanico, Cristine Quiason, Ksenija Radic, Luca Rappez, Lavigne Regis, Marina Reuter, Angelos Rigopoulos, Edita Ritmejeryte, Andreas Roempp, Livia S. Eberlin, Veronika Saharuka, Denis Sammour, Marta Sans, Kaija Schæpe, Julian Schneemann, Danielle Scott, Kumar Sharma, Bindesh Shrestha, Nicholas Sing, Renata Soares, Emilia Sogin, Jens Soltwisch, Berhard Spengler, Nicole Strittmatter, Na Sun, Zoltan Takats, Dinaiz Thinagaran, Spencer Thomas, Sergio Triana, Yury Tsybin, Lulu Tucker, Daa Van den Bosch, Quentin Vanbellingen, Dusan Velickovic, Claire Villette, Michæl Waletzko, Samantha Walker, Eric Weaver, Jake White, Guanshi Zhang, Jialing Zhang Alexandrov team Katya Ovchinnikova, Lachlan Stuart Vitaly Kovalev, Renat Nigmetzianov Luca Rappez, Sergio Triana Veronika Saharuka, Aslihan Inal Mohammed Shahraz Angelos Rigopoulos Prasad Phapale, Don Nguyen Ex: Andrew Palmer, Artem Tarasov Dominik Fay, Sergey Nikolenko Ivan Protsyuk, Sergey Ryazanov