Date post: | 08-Jan-2017 |
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Health & Medicine |
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How do you handle data from multiple chemistry sources? Find out how Reaxys made it easier
June 2016
Olivier Barberan
Putting Data to Work |
Data-driven drug design and research
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• General descriptor-property relationships • Sub-structural alerts • QSAR • Matched Molecular Pair analyses • Predictive pharmacology Etc…
Cumming, J.G., Davis, A.M. et al. Nat. Rev. Drug Disc. (2013) 12, 948–962
Data Knowledge Analysis
Predictions
• Data normalization • Taxonomies • Quality control Etc…
“Those who cannot remember the past are condemned to repeat it.” George Santayana: Life of Reason, Reason in Common Sense, Scribner's, 1905, page 284
ELSEVIER
Putting Data to Work |
Transforms Data and Knowledge to Real Research
Select the right compounds, active to right targets for right patients
Stay tuned for advanced research and competitor’s work Access data, interpret data, act on data for incisive decision
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Putting Data to Work | | 5
The current information retrieval solution at
Project chemists & modelers
Questions: • Any Information
for my target? • Any compounds
similar to my ligand
• Any new MOA for my disease?
Output: • Manual collected
customized file • Up-to-search date
data • Multi-sources
Take days to weeks
Expert searchers
Where Science Intersects with Business – Creating Business Dashboards That Combine Data from
Multiple Sources Presented at Bioit World 2015 by H. Wang,E. Gifford,
M. Clark
Putting Data to Work |
Reaxys/RMC KNIME and Pipeline pilot new nodes
- 4 new KNIME nodes and Pipeline pilot components are available - Covering Bioactivities, Citations, Reactions and Substances searches - API Access is needed to use Reaxys/RMC KNIME and Pipeline piltot Nodes
Reaxys KNIME Nodes are compatible with Version 2.12 and 3.1x
- Reaxys PP Nodes are compatible with Version 9.5
Putting Data to Work |
Summarize Latest Information (Patents, Articles) about Cancer using Reaxys and RMC API and Pipeline pilot
Latest Patents, journal articles, compounds, reactions related to • Target • Indication • Compound
Summary of new Data for last 30 days
Putting Data to Work |
Compound Assays for a Given Target (p38b) using RMC API and Pipeline pilot
Lists assays, results, assay details • Enhance with clustering by structure • Include in-house information
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Putting Data to Work |
Roche : Business Case
What - Improve efficiency of research. Synthesis planning Publication authorship Patent submission
Why - Save time and money. Short-term spend, long-term benefit
How - Reduce user interfaces and eliminate slow software. Decommission ISIS/Host, circumvent ELN search
Who - A highly functional collaboration. Arcondis Group Elsevier Information Systems GmbH F. Hoffmann-La Roche NextMove Software Ltd.
Putting Data to Work |
Electronic Lab
Notebooks
Data Capture, Normalization and
Integration
Reaxys Data
Unified discovery
interface for researchers
Challenge: Chemistry information is housed in separate databases, leading to inefficient research and escalating costs. Need integration of data to accelerate research and increase discoverability.
Roche Challenge
Putting Data to Work |
https://reaxys.roche.com
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
Putting Data to Work |
• Customer Feedback
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
• Several advantages of going for an implementation of the flexible approach:
• Additional data sources have been added
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Reaxys – Electronic Lab Notebook interoperability
The Reaxys team currently works in partnership with three major ELN providers:
PerkinElmer (formerly CambridgeSoft), Accelrys/biovia and IDBS
Run query from within
the ELN
Import reaction or
substance
Browse, navigate and
refine in Reaxys
Select and export
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Putting Data to Work |
Integrating E-notebook data with published data
• E-notebooks are an important mechanism to capture intellectual property
• Not optimized for data exploration
• Reaxys interface is optimized for data retrieval
• Filtering
• Cross-linking
• Search trail
• Links to source full-text
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Putting Data to Work |
Integration of assay data
• E-notebooks are primary data storage
• Have only internally-generated data
• Integration allows access to “all known data” with one search
• Link structures and data
• Handles target name synonyms
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Putting Data to Work |
Integrated Solution Search
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List of integrated sources
Sources list can include licensed databases, and multiple e-notebooks from organizational units All e-notebooks can be integrated and searched together
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Ligand Based virtual Screening to Identify New T-Type Calcium
Channel blockers (Cav3.2)
Objective : Describe an In Silico Screening approach using Reaxys Medicinal Chemistry
(API and Flatfile) to identify new T-Type Calcium Channel blockers
130 Active compounds
on Cav 3.2 (affinity <0.1 µM)
Flat file
Representation & Chemical Space Molecular descriptors & Fingerprints
Virtual Screening Pharmacophoric Similarity
N
O
N
NN
O
N
N
N
"Drug-like" Filtering
1. Molecular diversity and chemical originality
2. Compounds availability
1
2
3
4
5
1) Searching for Active Compounds on Cav3.2 ( affinity < 0.1µM)
Channel in Reaxys Medicinal Chemistry Using KNIME/Pipeline pilot
2) Build a pharmacophoric similarity Model based on Active
compounds found in RMC
3) Use of the Reaxys Flat file as an External Chemical source
4) Drug like filtering of potential Cav3,2 blockers
5) Biological testing on Cav3.2
API/KNIME/Pipelinepilot
314 Hits
39 Tested
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Biological testing of the 39 Hits on Cav3.2
Electrophysiology experiments: Screening @10 µM on Cav3.2 T-Type channels
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 29 30 31 32 33 34 35 36 37 38 39 0
25
50
75
100
Pe
ak
cu
rre
nt
inh
ibit
ion
(%
)
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9 compounds with a % inhibition > 75%
15 compounds with a % inhibition >50%
Compound # (@ 10µM)
Reaxys medicinal chemistry supports Ligand based virtual
Screening approaches
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
Target-directed and Phenotypic screening: parallel pathways to the
same goal
Phenotypic screening identifies compounds
that produce a biological response in a cell
or animal model
Target screening identifies
compounds that produce a biological
response on an isolated target
Phenotype - led vs. Target - led
However, a drawback is the need to use time-consuming genetic, chemical and/or
biophysical methods to identify the targets of compounds that are active (Target
deconvolution)
Phenotypic screening can find molecules that have more optimized drug-like
properties (such as cell penetration) than target-based screens.
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Scenario Melanoma cells predominantly occur in skin. Melanoma is less common than
other skin cancer. However, it is much more dangerous if it is not found in the
early stages. It causes the majority (75%) of deaths related to skin cancer.
Which are the targets involved in proliferation of melanoma cells lines ? And
which substances are acting on ?
Melanoma Cells
Search In RMC
Which Targets are involved in melanoma cells proliferation ?
Target Fingerprint of A 375 Melanoma cells based on Similar Compounds
996
molecules
Cell line A375
IC50 <= 1µM
3525 molecules
+In vitro Biological
results on targets
In vitro Biological
results on targets
Define activity class of
compounds
active / inactive on target
Target active
ratio calculation
3525
molecules
Chemical Similarity
Search 85%
For each compound and its given target:
Compound_Active_Ratio = (#Actives) / (#Actives +
#Inactives)
Active if Active_Ratio ≥ 0.8
Inactive if Active_Ratio ≤ 0.2
For each Target, count the number of Active and Inactive
molecules
Target_Active_Ratio = (#Actives - #Inactives) / (#Actives
+ #Inactives)
Target Fingeprint of A375 based on similar Compounds
(85% similarity)
#Molecules >= 20
Average Activity
Rate in RMC
Key Take Away
Using Reaxys API and Pipeline pilot an automated process was set up to
establish a target FingerPrint for disease specific cell lines.
Reaxys Medicinal chemistry provides High Quality data to identify
pharmacological targets involved in phenotypic screening and understand the
molecular mechanisms of action of drugs (MMOA).
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
Reaxys API/KNIME/Pipelinepilot
« In silico Screening »
Reaxys API/KNIME/Pipelinepilot
Reaxys API/KNIME/Pipelinepilot
Reaxys API
| 35
Customer problem
• In drug development, we need to screen large chemical libraries to identify compounds with desired properties
• Instead of experimentally testing all compounds, an in-silico pre-screening is usually performed
• For the in-silico pre-screening process, we need to have powerful predictive models in hand
• Such models are constructed using experimentally derived data
The Elsevier solution
• Reaxys is the most comprehensive source for experientally derived information on chemical compounds
• This information can be used to construct high-performance predictive models
• The best way to retrieve the required information from Reaxys is using the Reaxys API which can be accessed from Knime or PipelinePilot
• Elsevier provides readily usable Knime and PipelinePilot components
Your problem… and our solution
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Building a QSAR model for α-Chymotrypsin activity
Using KNIME
For training the
model, we retrieved
~ 5.000 quantitative
bioactivity data
points for “Alpha
Chymotrypsin”
extracted from RMC
using the API
With an error rate of
0.2 the model
predicts for new
compounds if they
are active or not
Putting Data to Work |
Reaxys Provides a Unified Information Portal
•Provides a single powerful interface
•Can integrate several notebook systems
•Links chemistry, structures, sourcing, citations, and full-text of articles
Reaxys API/KNIME/Pipelinepilot (Professional Services)
« Self service »
Data Integration into Reaxys (Professional Services)
In House Data Integration (RMC Flatfile)
« Discoveryconnect »
Data Integration of Reactions into Reaxys (Professional Services)
API/KNIME/Pipelinepilot
« In silico Screening »
API/KNIME/Pipelinepilot
API/KNIME/Pipelinepilot
Reaxys API