Department of Bioinformatics - BiGCaT

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Mapping experimental metabolomics

data to biological pathways

Egon Willighagen, Martina Kutmon, Chris Evelo

@egonwillighagen, 0000-0001-7542-028619 April 2016, Lunteren

Department of Bioinformatics - BiGCaT

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Visible Metabolome: NMR of blood

Gowda et al. Anal. Chem. 2010 82(21):8983 doi:10.1021/ac101938w

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“Smellable” Metabolome: Asthma

Smolinska et al. PloS ONE. 2014 9:e105447. doi:10.1371/journal.pone.0105447

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We see a lot? But what is it?

• Current techniques can see up to 1000 metabolites in one analysis–Only part of all 40k metabolites

• Only 10% we can identify–The other 90% is unknown

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PathVisio: pathway enrichment (etc)

Van Iersel, M.P., et al. "Presenting and exploring biological pathways with PathVisio." BMC bioinformatics 9.1 (2008): 399. http://pathvisio.org/ Martina Kutmon→

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Switching identities: Warfarin

Porter, W. (2010). Warfarin: history, tautomerism and activityJournal of Computer-Aided Molecular Design, 24 (6-7), 553-573DOI: 10.1007/s10822-010-9335-7

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Data set #1: breath metabolites

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Data set #2: Brainshake Ltd.

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Data set #3: troglitazone (on heme biosynthesis)

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m/z to structure?

Peironcely et al. JChemInf 2012 4:21 doi:10.1186/1758-2946-4-21

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How accurate are metabolite characterizations?

Elyashberg et al. Structure Revision of Asperjinone UsingComputer-Assisted Structure Elucidation MethodsJ. Nat. Prod., 2013, 76 (1), pp 113–116, DOI: 10.1021/np300218g

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Bridging: identifiers

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So, what IDs are used in WikiPathways?

Curated Collectionsubset

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Van Iersel, M.P., et al. "The BridgeDb framework: standardized access to gene, protein and metabolite identifier mapping services." BMC Bioinformatics 11.1 (2010): 5.

New tools● Open PHACTS' IMS● Bioclipse● R package

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Metabolite ID Mapping database● HMDB● ChEBI

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Wikidata

Mietchen, D. et al. Enabling open science: Wikidata for research (Wiki4R). Research Ideas and Outcomes 1, e7573+ (2015)

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Wikidata

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What if we add more CAS ID mappings? (e.g. from Wikidata)INFO: Number of ids in Ch (HMDB): 41514 (changed +0.0%)INFO: Number of ids in Ce (ChEBI): 64222 (changed +0.0%)INFO: Number of ids in Kd (KEGG Drug): 2406 (changed +23960.0%)INFO: Number of ids in Ca (CAS): 38621 (changed +30.5%)INFO: Number of ids in Wi (Wikipedia): 3991 (changed +0.0%)INFO: Number of ids in Ck (KEGG Compound): 15896 (changed +0.0%)INFO: Number of ids in Cpc (PubChem-compound): 29170 (changed +72.5%)INFO: Number of ids in Wd: 18237INFO: Number of ids in Cs (Chemspider): 23981 (changed +49.4%)

- 30% more CAS numbers (294 unique IDs in WikiPathways)- 73% more PubChem compound identifiers (217 unique IDs in WP)- 50% more Chemspider identifiers (157 unique IDs in WP)- a lot more KEGG Drug identifiers

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Switching identities: Glucose

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Acid/Base conjugates

CHEBI:15361 (Pyruvate) -> Ce:CHEBI:32816 (conjugate) -> Ck:C00022 -> [WP2456 HIF1A and PPARG regulation of glycolysis, WP2453 TCA Cycle and PDHc]

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BridgeDb: scientific lenses

• Gene– gene-protein– gene-probe

• Metabolite– Tautomers– Compound class– Charge (acid/ate)

Brenninkmeijer, CYA, et al. "Scientific Lenses over Linked Data: An approach to support task specific views of the data. A vision." Proceedings of 2nd International Workshop on Linked Science. 2012.

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#1: The breath data set

CAS numbers: 1843

CAS numbers with mappings: 960

CAS numbers matches: 251

Pathways found: 499 (unique: 165)

Matches via CAS: 9

Matches via mapping: 92

Matches via ChEBI super class: 300

Matches via ChEBI charged species: 31

Matches via ChEBI tautomers: 0

Matches via ChEBI roles: 67

CAS: 544-63-8 (myristic acid) Ce:28875 Ce:15904 (long-chain fatty → →acid) [WP368 Mitochondrial LC-Fatty Acid Beta-Oxidation,→

WP357 Fatty Acid Biosynthesis]

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#2: Brainshake Ltd.

ChEBI numbers: 40ChEBI numbers with mappings: 40ChEBI numbers matches: 19Pathways found: 32Matches via ChEBI: 6Matches via mapping: 21Matches via ChEBI super class: 0Matches via ChEBI charged species: 5Matches via ChEBI tautomers: 0

CHEBI:16113 (Free cholesterol) Ca:57-88-5 [WP430 Statin → →Pathway, WP299 Nuclear Receptors in Lipid Metabolism and Toxicity, WP197 Cholesterol Biosynthesis, WP237 Glucocorticoid & Mineralcorticoid Metabolism, WP496 Steroid Biosynthesis]

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Conclusions

• Updated metabolite ID database–HMDB: still a major workhorse–ChEBI: charged species,

compound classes–Wikidata: CAS numbers, other

missing

• Pathway Analysis–Mapping with Bioclipse and

PathVisio–Scientific lenses improve mappings–Better annotation, Z-Score

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Acknowledgements

• WikiPathways and PathVisio projects– Prof. Alex Pico's team, UCSF

– Current and past members (Andra Waagmeester, Martijn van Iersel)

– Pathway Providers: Pieter Giesbertz (TUM), Kozo Nishida (RIKEN)

• Maastricht University– Toxicology: Rianne Fijten

– MaCSBio team

• Open PHACTS– Manchester University: Prof. Carole Goble, Christian Brenninkmeijer, Stian Soiland-Reyes

– Heriot-Watt University: Alasdair Grey

– Royal Society of Chemistry: Colin Batchelor

• Others– HMDB, ChEBI, Wikidata teams

– Bioclipse: Ola Spjuth (Uppsala University)

– MetaboLights collaboration: Reza Salek, Chandu Venkata, Garima Thakur