ICIC 2013 Conference Proceedings Sebastian Radestock

DR. S. RADESTOCK | 14 OCTOBER 2013 | MAKING HIDDEN DATA DISCOVERABLE

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DRUG DISCOVERY TODAY

ELN

Biology

Therapeutic

target

Chemistry

Check chemical feasibility

Synthesize or buy

Test

Check ADME/Tox

Report

Analyze SAR

Generate chemistry ideas

In-house

Knowledge

survey

ELN

DBs

Flatfiles

Journals &

Patents

Journals

Docs

Known ligands

http://www.rcsb.org/pdb

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Dr. Sebastian Radestock

Product Manager Reaxys

Elsevier Information Systems GmbH

Frankfurt am Main Germany

MAKING HIDDEN DATA DISCOVERABLE:

HOW TO BUILD EFFECTIVE DRUG

DISCOVERY ENGINES?

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DRUG DISCOVERY TOMORROW

Therapeutic

target

Chemistry


Synthesize or buy

Test

Check ADME/Tox

Report

Analyze SAR


In-house

Knowledge

survey

ELN

Known ligands

DBs

Journals &

Patents

ELN

Flatfiles

Docs

Biology

Federated

search system

Chemistry

integrator

Biology

integrator

Integrator for

biomedical

data

Literature

management

tool

Integrator for

drug safety


TWO APPROACHES TO SOLVING THE CHALLENGE OF DATA ACCESS


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ELN ELN

Storage and capture Capture

FEDERATED MODEL

WAREHOUSE APPROACH

Storage Analysis

system

User

CHEMISTRY INTEGRATOR

In-house


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EXAMPLE IMPLEMENTATION OF THE FEDERATED MODEL

Storage and capture

FEDERATED MODEL

Analysis

system

User


In-house

Expansion of the existing system by integrating Reaxys

Existing system for consolidating in-house structure and bioactivity data

CONTAINS ALL PUBLISHED AND HISTORICAL CHEMISTRY DATA


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THE REAXYS DATA BASE

• Compounds, substance property

data, preparations, reactions, and

bibliographic information…

…from 400 core chemistry journals

…from relevant chemistry patents

• Manual extraction of all the data

• Coverage of 500 property data fields,

from basics like boiling point or

melting point, via crystal data and

magnetic properties, to spectra

• All together 750 million data points

• Historical chemistry data…

…dating back to 1771

Scie

nti

fic d

ata

model

SUPPORTING MULTI-DISCIPLINARY RESEARCH


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EXPANDED BIBLIOGRAPHIC CONTENT IN REAXYS

• Bibliographic data from 16.000

periodicals covering chemistry and

related sciences have been loaded

into Reaxys

• This goes beyond journals and

patents, it includes conference

proceedings, business articles,

reviews etc.

AGRICULTURAL AND BIOLOGICAL SCIENCES

BIOCHEMISTRY, GENETICS AND MOLECULAR BIOLOGY

CHEMICAL ENGINEERING

DENTISTRY

EARTH AND PLANETARY SCIENCES

ENERGY

ENGINEERING

ENVIRONMENTAL SCIENCE

IMMUNOLOGY AND MICROBIOLOGY

MATERIALS SCIENCE

MEDICINE

NEUROSCIENCE

PHARMACOLOGY, TOXICOLOGY AND PHARMACEUTICS

PHYSICS AND ASTRONOMY

VETERINARY

ETC.

old

new

THE NEXT STEP… COMING 2014


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REAXYS-TREE AND AUTOMATIC INDEXING

Title/Abstract

The Biosynthesis of Aristeromycin. Conversion of Neplanocin A to

Aristeromycin by a Novel Enzymatic Reduction

Partially purified cell-free extracts of the aristeromycin producer

Streptomyces citricolor have been shown to catalyze the NADPH-

dependent reduction of neplanocin A to aristeromycin. Stereochemical

studies revealed that the reduction proceeds with anti-geometry and

involves transfer of the 4 pro-R hydrogen atom of NADPH to the 6'β

position of aristeromycin.

Reaxys Keywords: Aristeromycin – biosynthesis, enzymatic

reduction, Neplanocin A

Index for chemistry terms

Translate chemical names into structures and make them searchable

Step 1

Add chemistry relevant keywords and identified chemical entities

Step 2

Step 3

https://www.reaxys.com/reaxys_new/secured/paging.do?performed=true&action=restore

ACCESS TO REAXYS IS VIA THE REAXYS APPLICATION PROGRAMMING INTERFACE (API)


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FEDERATED SEARCH SYSTEM WITH REAXYS LOOK-UP

How should the API look

like?

LESSONS LEARNED


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THE REAXYS APPLICATION PROGRAMMING INTERFACE (API)

• Customers want to have access to all data in Reaxys

• Substances and substance property data

• Reactions and reaction details

• Citations

• Customers want to have access to all functionality of Reaxys

• Exact structure and reaction searching, similarity and substructure searching

• Factual queries

• Further processing of hitsets

• The Reaxys API was designed to be based on exchanging XML code between the user

and the Reaxys server via HTML POST requests

• Security and usage tracking is an issue

• Secure communication via HTTPS POST is supported

• The Reaxys API is stateful, and login is required

In-house

SOME DISADVANTAGES TO CONSIDER


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LIMITATIONS OF THE FEDERATED MODEL

Storage and capture

FEDERATED MODEL

ELN

Analysis

system

User


In-house

Architecture allows easy expansion when new data source becomes available

Performance and availability of the system is dependent on the source systems

No clean-up and normalization of the data


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EXAMPLE IMPLEMENTATION OF THE WAREHOUSE APPROACH

Storage

Capture

WAREHOUSE APPROACH

Analysis

system

User

In-house

Bioactivity data was normalized, and structures were de-duplicated

A customer set up a system that contains structure and bioactivity data, and IP information

All data was extracted, translated and loaded to fit into one unified data model (UDM)


Structures

http://upload.wikimedia.org/wikipedia/commons/a/a1/Chembl_logo.png


STRUCTURE DATA FROM REAXYS COMES FROM THE REAXYS STRUCTURE FLAT FILE


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PLATFORM FOR STRUCTURE AND BIOACTIVITY DATA

SOME DISADVANTAGES TO CONSIDER


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LIMITATIONS OF THE OF THE WAREHOUSE APPROACH

Storage

Capture

WAREHOUSE APPROACH

Analysis

system

User

In-house

Long implementation time and associated high cost

Difficult to accommodate differences or changes in data types


Structures



A CONTENT INTEGRATION SOLUTION THAT IS NOW AVAILABLE TO ALL REAXYS USERS


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EXAMPLE IMPLEMENTATION OF A FLEXIBLE APPROACH

Capture

FEDERATED MODEL

WAREHOUSE APPROACH

User Structures from PubChem and eMolecules have been integrated into Reaxys

Storage and capture

Pricing

Real-time commercial availability and pricing information comes via an eMolecules API

Structures

Structures

Storage

Using multiple storage systems eliminates the need for one UDM


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The substance crosslinking

icon allows to switch to

corresponding substances in

other data sources

Results are available from

different data source tabs

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Filter for substances that

are/aren’t contained in

other data sources



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Filter for substances that

are/aren’t contained in

other data sources



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The commercial availability

icon allows to check real-time

pricing information from

eMolecules

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PubChem property

headers with direct

links to PubChem

LESSONS LEARNED


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FLEXIBLE APPROACH FOR INTEGRATION

• Reaxys has proven to be extremely powerful as analysis and database system

• Separation of the data from different data sources into multiple storage

systems is the way to go…

• … if a powerful crosslinking mechanism is in place

• Some pieces of information that are subject to frequent updates should be

integrated using the federated model

A CONTENT INTEGRATION SOLUTION THAT ELSEVIER BUILT FOR ROCHE


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EXAMPLE IMPLEMENTATION OF A FLEXIBLE APPROACH

FEDERATED MODEL

WAREHOUSE APPROACH

User Integration of Roche proprietary data on chemistry experiments

Storage and capture

Pricing

Reaxys with PubChem and eMolecules integrated

ELN In-house Reactions

Capture

Structures

Structures

Storage


THE SITUATION AT ROCHE YESTERDAY… AND TODAY


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INTEGRATION OF ROCHE IN-HOUSE DATA

https://reaxys.roche.com

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Normalized

Roche-specific

reaction data

Data on references

and/or experiments,

including PDF links

Roche-specific data is included in

the Output (PDF, MS-Word etc.)

Filters on

Roche-specific

data fields

Up to four Roche reaction

data sources are supported


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A Roche icon allows

to switch to a Roche

in-house repository

The reaction crosslinking icon

allows to switch to

corresponding reactions in other

data sources

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Start building a synthesis tree by

clicking on the synthesize link


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Synthesis planner

opens up

The first step of the synthesis

plan is selected from the

Roche data source

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One step has

been added


Add a second

step

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New reactions are

loaded


The second step of the

synthesis plan is

selected from Reaxys

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Roche

Experimental details of the

“mixed” synthesis plan are

summarized in a table.

Another step has

been added


CUSTOMER FEEDBACK


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INTEGRATION OF ROCHE IN-HOUSE DATA

• Usability and acceptance tests by Roche

showed:

• Increased productivity of researchers at

Roche

• Increased discoverability of the Roche

reaction content

• Reduced maintenance effort for Roche:

• Legacy systems were decommissioned

• Roche gets on-going maintenance and

functionality improvements by Elsevier

• Not compromise in security

• Flexible approach:

• Additional data sources have been

added

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Therapeutic

target

Chemistry


Synthesize or buy

Test

Check ADME/Tox

Report

Analyze SAR


In-house

Knowledge

survey

ELN

Known ligands

DBs

Journals &

Patents

ELN Flatfiles

Docs

MedScan

Biology

Federated

search system


THANK YOU – QUESTIONS?

Dr. Sebastian Radestock Product Manager Reaxys

Elsevier Information Systems GmbH Frankfurt am Main, Germany

[email protected]

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ICIC 2013 Conference Proceedings Sebastian Radestock

Technology

data coverage

crystal data

property data fields

new data source

reaxys api

reaxys keywords

reaxys substances

reaxys server