ChemSpider: Connecting Chemistry and Mass

Spectrometry on the Internet

Antony Williams and John Shockcor

A Vision for Our Time

Analysis of body fluids can lead to earlier diagnosis

Analysing the “Metabolome” improves the opportunities for personalized medicine

Coupled analytical instrumentation with chemical and bio informatics…

It’s about structures…

Drugs, metabolites, pesticides – it’s all about chemical structures

RSC hosts a community resource for chemistry to support chemists

Chemical compounds, properties, syntheses, analytical data, publications..

Public Domain Chemistry Databases

Online databases can be messy and inconsistent

Non-curated databases proliferate errors

Original sources of errors hard to determine

Data validation is time-consuming, challenging and exacting

The structure of Vitamin K1 is ???

Vitamin K1

ChemSpider A free internet database

25 million chemicals from 400 data sources

Data includes: Chemical identifiers Links to publications Links to patents Experimental and predicted properties Spectral data

For Synthetic Chemists

For NMR Spectroscopists

Community Contribution Community-based deposition of data

Structures, spectra, links, properties

Community crowdsourced curation Validating and curation data

>130 people have contributed data, skills and experience Synthesis procedures Spectral data

A flexible platform for...

Searching – many tens of thousands of searches per day

Teaching - providing data and resources to help teach chemistry

Integration - available for third parties to take value from the data

For Mass Spectrometrists Valuable searches for Mass Spec would

be:

Search the database by mass or formula for structure identification

Search subsets of data – “metabolism”

Link structure-based data across the internet

Provide “programming interfaces”

What is Metabonomics?

Metabonomics “…measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification…” Nicholson et al., 1999

Full Metabolic Pathway Chart

Kreb’s Cycle

What is Metabonomics or Metabolomics? Analytical data on two groups of samples which

we suspect may be different, can we determine the following information?

Are the groups different?

Detect those compounds which have increased or decreased in concentration in each group.

Detect those compounds which are missing from or unique to each group.

Direct Infusion of Urine into a Mass Spectrometer

UPLC Lipid Class Separation

PC, SM, PG, PE, DG

ChoE & TG

lyso-PC, lyso-PE

Hybrid High Resolution QTof MS

High Resolution MS of a TAG

Extracted Ion Chromatogram of m/z 874.7898

MarkerLynx PCA Analysis of Data Transgenic Mice Study

PCA Loadings

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Scores Comp[1] vs. Comp[2] colored by Modification subsets

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EZinfo 3 - Heart TG mouse 4_106.usp (M1: PCA-X) - 2010-10-03 13:15:14 (UTC-5)

PCA Scores

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Loadings Comp[1] vs. Comp[2]

EZinfo 3 - Heart TG mouse 4_106.usp (M1: PCA-X) - 2010-10-03 13:52:36 (UTC-5)

m/z_RT Pairs Which Describe the Variance Between Transgenic and Wild Type Mice

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Loadings Comp[1] vs. Comp[2]

806.5713

874.7898

EZinfo 3 - Heart TG mouse 4_106.usp (M1: PCA-X) - 2010-10-03 13:41:05 (UTC-5)

Trend Plot of Those m/z_RT PairsY-axis is the Area of the XIC

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Variable Trends colored by Modification subsets

EZinfo 3 - Heart TG mouse 4_106.usp (M1: PCA-X) - 2010-10-20 09:47:43 (UTC-5)

Calculation of Elemental Composition & ChemSpider Search of Lipid Maps Database Performed via MarkerLynx

Results of the ChemSpider Search in the MarkerLynx Worksheet

Hit Details in ChemSpider

Hybrid High Resolution QTof MS

Lipid at RT 4.41 with m/z 806.5695 PC 16:0/22:6

16:0

22:6

Phospholipids Elevated in Transgenic Mice

What Have We Done?

Turned “Data into Information”

Now to turn information into knowledge

We want to visualize our metabolite information and information from other “omics” techniques using modern “pathway” tools. (Systems Biology)

Why Do I Like ChemSpider?

It is open to all the scientific community not just a select few.

It relies on expertise from the scientific community for expansion, curation and improved functionality. Let us work together!

It is always with me…

Linking and Enabling

Clearly mass spectrometry facilitates deeper understanding of metabolomics

The ChemSpider database is a rich foundation for structure-based analysis

Community support through data deposition and curation is very enabling

Ideas for Future Work

Extend search capabilities

Expand existing databases

Integrate to metabolic pathways tools

Thank You!!!