Open innovation in the agri-food sector Mark Forster Syngenta R&D Chemical Research March 2015

Classification: Public

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Outline of presentation.

Software

Free / Libre Open Source Software (FLOSS)

Scientific open source

Open source in Syngenta

Open access data

Chemical data resources

Data searching and comparison

Projects

OpenPHACTS

Elixir

Chemical screening

Plant science data sharing

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Software.

Free / Libre Open Source Software (FLOSS)

Open source, code freely available, available freely

Free - No (license) cost, gratis, free as in beer.

Libre - Free to modify, distribute, free as in speech.

Copyright - Protect rights of copyright holder, re: distribution

Copyleft - Protect author rights for sharing, derivative works

Licenses

Permissive - e.g. BSD, Derivative code can be closed,

sold, not shared.

Restrictive – e.g. GPL, Derivatives open, community orientation,

binary distribution optional.

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Examples of open source.

From the smallest device to the largest supercomputers

From the smallest to the largest companies

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Scientific open source.

Long history – QCPE (1962)

Sourceforge, Google Code (2012)

Essential for reproducible science

Benefit of easier large scale deployment (cloud)

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Open source in Syngenta.

Codes for docking or MD can be cumbersome

- Text file input / output, editing required !

Solution was to ‘automate’ editing using PERL

Can the automation script be released ?

Issues: Warranty , Liability, Support, Host, IP ours/3rd party

Outcome: Code released 2007

First ‘official’ open source release by Syngenta

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Open source in Syngenta.

Contribute to existing projects

Mzmine – GCMS metabolomics

Create new projects

LICSS - Chemical features in Excel

PDBclimb - 3D command line molecule builder

2011 - Simplified process

Open source checklist

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Open source in Syngenta.

Sponsor / support industry and academic open source dialogue

Wellcome Trust, EBI Industry programme funded ‘retreat’ meetings:

2011 – Molecular Informatics Open Source Software (MIOSS)

2012 – Systems, pathways, interactions, networks (SPIN-OSS)

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Open access data in Syngenta.

We use public life science data of many relevant types

Genome Transcriptome DNA/RNA sequence

Protein sequence Protein structure Chemical bioactivity

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Elixir – European Life Science Infrastructure.

The pan European sustainable life science data infrastructure.

Supporting life science research, applications and industry.

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Open access chemical structure / property data

Discuss three significant open access chemistry resources:

Chemspider (RSC) , Pubchem (NIH) , ChEMBL, ChEBI (EBI).

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Chemical data resources

Chemical data resources are 10Ms of structures

Manage ‘large’ chemical structure data sets

eMolecules February 2015 catalogue - 7M

Syngenta corporate – several million.

Syngenta vendor cumulative – 25M+

ChEMBL (public bioactivity data) – 1.4M

SureCHEMBL (patent data) – 15M

Zinc ‘All Purchasing’ – 19M

Zinc ‘Boutique’ – 12M

Enamine virtual catalogue - 26M

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Open access chemical structure / property data

ChEMBL target based search.

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Open access chemical structure / property data

ChEMBL – filter for most active compounds against given target

Individual compound record

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ChEMBL – Pesticide data integration.

ChEMBL public bioactivity data source.

Curated data from medicinal chemistry literature

Syngenta - ChEMBL collaboration:

Pesticide focused literature curation January 2013-June 2013

Data quality control and review – July 2013-June 2014.

28k compounds

not in ChEMBL

Data public

availability in

August 2014

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Chemical data set comparisons.

International Chemical Identifier (InChI)

Developed by IUPAC / NIST

Unique textual identifier for chemical structures

Generated by an algorithm not a committee or authority.

Ethanol CH3CH2OH

SMILEs CCO

InChI=1S/C2H6O/c1-2-3/h3H,2H2,1H3 (standard InChI)

InChI Key LFQSCWFLJHTTHZ-UHFFFAOYSA-N

Utility: Uniquely valuable for chemical identity checking, and cross

linking of same structure in different data sets.

Sophisticated treatment of stereoisomerism, salts, tautomers,

isotopes etc. Now used in Syngenta registration, much faster than

at pre-checking identity than pure commercial solution.

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Chemical data set comparisons.

Fast similarity search: Openbabel search index (fs file) creation

Perl scripted search of data in SMILEs format

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Open innovation in plant sciences

Donate data to open access public resources

Rice genome sequence (Goff et al. 2002)

Tomato sequencing (Sato et al. 2012)

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Open innovation in plant sciences

1999 – A strain of wheat stem rust identified in Uganda (Ug99).

Identify disease resistance markers and related genes.

Germplasm freely available to wheat breeding organizations.

CIMMYT, Syngenta, Cornell University, Gates Foundation.

‘A breakthrough in breeding technology for wheat rust.’

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Open innovation – chemical screening.

IVCC – Innovative vector control consortium.

Screening of Syngenta compounds for anti-mosquito activity.

Public-private partnership funded by Gates foundation.

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Open innovation – chemical screening.

Liverpool school of tropical medicine , neglected tropical diseases (NTD)

Screening of Syngenta compounds for Plasmodium / TB activity.

Agreed project (early stage).

Chemistry donated in non competing field.

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Open innovation – chemical data integration.

• Open pharmacalogical concept triple store – http://www.openphacts.org

• EU (IMI) and pharma company funded (16M USD, 3.5 years)

• Use ‘semantic web’ methods to integrate data across R&D process.

• Commercially hosted data store (public data), agreed ontologies.

• Exemplar applications (commercial and/or open source)

• Now OpenPHACTS foundation.

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Acknowledgements.

All colleagues engaged in the work presented here:

M.Robinson (Syngenta foundation)

P.Wege (IVCC, LSTM, ChEMBL)

M.Earll , C.Pudney, M.Seymour (Mzmine)

K.Lawson (LICSS Speadsheet)

S.Albinson (Open source checklist)

B.Dietrich, R.Cade (Tomato)

S.Goff & team (Rice)

OpenPHACTS team

J.Overington and staff of EBI / Elixir

And any others I have missed.

Questions?