skolnik symposium acs meeting philadelphia 2016

Steve Bryant Evan Bolton

Thanks, Steve!

The Software Years

1992

• CAS (and meters of books)

• Access through STN via IBM 3270 terminal emulation and cryptic commands

• Beilstein Database (and meters of books)

• No open source software libraries for cheminformatics

Computer-Assisted Structure Elucidation

(CASE)

Steinbeck, C.; Angewandte Chemie. International Ed. in English 1996, 35, 1984-1986

Steinbeck, C.: J. Chem. Inf. Comput. Sci. 2001, 41, 6, 1500

1992 - now

Successful Science requires

Data and Software to be

Free and Open

16 Years of the Chemistry Development Kit (CDK)

Christoph Steinbeck and the CDK Developers

http://cdk.sourceforge.net

The Chemistry Development Kit (CDK) Open Source Cheminformatics in Java

http://cdk.sourceforge.net/

The CDK after 16 years

•16,521 commits made by 115 contributors •564,171 lines of code•mostly written in Java •well established, mature codebase •maintained by a large development team •with stable Y-O-Y commits•estimated 151 years of effort (COCOMO model) •first commit in October, 2000 •most recent commit 1 day ago

The Chemistry Development Kit (CDK) Open Source Cheminformatics in Java

Bibliometrics

Try it: http://cdkdepict-openchem.rhcloud.com/

Error

1.4.

x1.

5.x

Examples 1-4: Clark A, et al, 2D structure depiction. JCIM, 46, 1107-1123 (2006)

1.5.x: Cleaner, More Efficient, More Robust, More Stable

Molecule 2D layout and rendering from SMILES

http://cdkdepict-openchem.rhcloud.com/

The Database Years

16

NMRShiftDB.org

The European Bioinformatics Institute

(EBI)

The European Molecular Biology Laboratory

(EMBL)

A basic research institute funded by public research monies from 20 member states.

The European Bioinformatics Institute

(EBI)

Intermission

Chris Steinbeck David Wild

Rajarshi Guha Egon Willighagen

Documenting the metabolomes of all

species on the planet

There are known knowns; there are things we know we know.We also know there are known unknowns; that is to say, we know there are some things we do not know.But there are also unknown unknowns – the ones we don’t know we don’t know.

—United States Secretary of Defense,

Donald Rumsfeld

http://en.wikipedia.org/wiki/United_States_Secretary_of_Defense

http://en.wikipedia.org/wiki/Donald_Rumsfeld

Chemical Entities of Biological Interest (ChEBI)

Additional data items for natural products

Species Variety Tissue

Links to ontologies and taxonomies

Links to citations, where available

ChEMBL–DataforDrugDiscovery

Bioactivity

Compou

Assay/

>Thrombin MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEK

3. Insight, tools and resources for translational drug discovery

2. Organization, integration, curation and standardization of pharmacology data

1. Scientific facts

Ki =

APTT = 11

The PubChem Collaboration

Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

Metabolites. 2016 Feb 15;6(1)

•8.7 mio eukaryotic species on earth (+- 1.3mio)

•8.7 mio eukaryotic species on earth (+- 1.3mio)•1.2 mio species identified and classified

•8.7 mio eukaryotic species on earth (+- 1.3mio)•1.2 mio species identified and classified•3000 - 4000 complete species genomes sequenced

•8.7 mio eukaryotic species on earth (+- 1.3mio)•1.2 mio species identified and classified•3000 - 4000 complete species genomes sequenced

What about completed metabolomes?

Species Metabolomes are being assembled on the fly

right now through data sharing in Metabolomics

Experimental Repository

Reference Layer

Chemistry Spectroscopy Biology

Ana

lysi

s To

ols

Primary Literature

Primary data and Meta-Data, Spectra, Protocols, Synopses, ...

MetaboLights Database at the EBI

Repository Entry

Reference Layer

7 most annotated metabolomes in MetaboLights

30 most annotated metabolomes in MetaboLights

1600 metabolome sizes in MetaboLights on a log scale

Slides athttps://www.slideshare.net/csteinbeck

Funding

Steve Bryant Evan Bolton

Thanks for your attention