This document provides an overview and introduction to Pathway Studio, a software tool that helps researchers understand disease biology. It describes how Pathway Studio addresses challenges across the research and development value chain from discovery to post-launch. It highlights how Pathway Studio utilizes a large knowledgebase derived from literature to provide pathways, networks, and tools for visualizing and analyzing experimental omics data. Examples of how Pathway Studio can be used for tasks like target discovery, biomarker discovery, and drug repurposing are also presented.

1. An introduction to
Pathway Studio
Helping researchers understand the biology
of disease…
Frank White, PhD
May 27, 2015

2. | 2
Pathway Studio addresses key challenges across the
R&D value chain
DISCOVERY
PRE-
CLINICAL
CLINICAL
POST-
LAUNCH
Product Name Mapping to
R&D Phase
Description
Pathway Studio Discovery Target Discovery, Biomarker Discovery, Drug
Repurposing, Biological Pathways, Gene
Expression, Genomics, Proteomics, Basic
Research
Preclinical Proteomics, Metabolomics
Translational /
Clinical
Patient Stratification
R&D Value Chain

3. | 3
Pathway Studio overview: Data, tools, visualization
Pathway Studio
ToolsKnowledgebase
Manually
curated
pathways
Ontologies
Biological
relations
extracted from
literature
Experiment analysis:
Gene expression
Proteomics
Metabolomics
NGS data
Search
Summarization
Navigation
Visualization
24M abstracts
3.5M full texts
4.8M relations
+836K new
relations

4. | 4
Pathway Studio databases cover wide ranging information
standard
name
standard
link
standard
name
Mammal
protein-centered
ChemEffect
drug-centered
DiseaseFX
biomarker-centered
+Biomarker
facts
+Drugs
Proteins +
• diseases
• clinical parameters
• small molecules
• cell processes
• treatments
• genetic change
• state change
• quantitative change
Cells*
cell-centered
+Cell facts
Cells

5. | 5
Benefits: Visualize and understand disease biology
• Pathway diagrams provide
a view of complex biological
processes.
• Pathway views provide
the context for analyzing
neighboring molecules
of a particular target.
• Drugs may work on a
neighboring molecule in
the pathway instead of the
intended target, so
understanding
relationships is critical

6. How can Pathway
Studio help you?

7. | 7
The benefits of more content…
• Pathway Studio has 3-5x more literature-derived content
than any other resource, so…
 No matter what disease you study, you’ll find 2-3 times
more connections and pathway members than any other
resource… if they have any results at all!
 You’ll find more references supporting those
relationships, so you’ll have higher confidence in the
meaning of your experimental results
 You’ll feel more confident about what’s reported in the
literature, with more independent references to help you
verify reported experimental results

8. | 8
Start with expertly-curated pathways…
Pathway Studio includes
almost 1500 expertly-
curated reference
pathways that you can
search, edit, and use to
interpret your
experimental data. And
new pathways are added
regularly…

9. | 9
Focus on what’s important to you…
Users can customize
how they interact with
data in Pathway Studio –
so they can focus on
specific types of data, or
subsets of data from a
particular experiment.
Keep focused on what’s
important to your
research…

10. | 10
How does Pathway Studio help your research?

11. | 11
Pathway Studio saves you time

12. | 12
According to our customers…

13. Pathway Studio
versus similar tools

14. | 14
Pathway Studio vs the Competition: Autophagy
101
175
39
91
20
34
16
73*
MetaCore
Pathway Studio - Raw
Ingenuity
Pathway Studio - Corrected
Proof Point: More content translates to more results for researchers
Adapted figure from
Lorenzi et al, 2014.
Used with permission.
Lorenzi P, Claerhout S, Mills GB, Weinstein JN. 2014 A curated census of autophagy-modulating proteins and small molecules. Autophagy 10:7, 1-11
0
50
100
150
200
250
300
350
400
450
MetaCore IPA Pathway
Studio
Unique
Shared
* - This data comes from early 2013. When the list of 73 “unique” IPA hits were checked
in PS in July 2014, more than 50 were now found – that’s the power of more content!
Some proteins and small molecules are found with
all solutions (shared), and each product finds
some unique interactions (unique).
But Pathway Studio finds 2-3X more than IPA,
and 10X more than MetaCore.

15. Pathway Studio vs the Competition: Apoptosis
Apoptosis results similar to Autophagy
Ingenuity Pathway Analysis
Pathway Studio
Lorenzi et al., 2015 unpublished
3487
2894
484
0
1000
2000
3000
4000
5000
6000
7000
IPA Pathway Studio
Unique
Shared
Pathway Studio finds twice as many total
results as Ingenuity, and 7X more unique
results

16. | 16
Why researchers need Pathway Studio
More content equals more confidence in your answers:
 Data collected from 5-8 times more full-text articles provides the needed
context and evidence to unravel even the most complex biological
processes
 Weekly updates - keeps researchers up-to-date with the latest research
 Largest collection of expertly-curated reference pathways provides a
starting point for complex model building and exploration
Analysis tools that provide deeper insights, better understanding
 Import your own content to leverage legacy data and in-house expertise
 Analysis wizards streamline everyday analysis, highlight most regulated
genes in minutes
 Advanced tools support creating de novo pathways from customer’s
experimental data to enable better ROI

17. Sample Pathway
Studio use cases

18. | 18
Target discovery
• Most comprehensive knowledgebase
enables more complete mapping of
in-house or public expression data to
pathways
• Simple data importing using step-by-
step wizards
• SubNetwork Enrichment Analysis
(SNEA) helps identify upstream
regulators of specific expression
patterns
• Drug mechanism of action models
facilitate identification of on-target
and off-target effects
Most researchers use Pathway Studio to analyze in-house experiments

19. | 19
Biomarker discovery
• Most comprehensive
knowledgebase, along with cellular
localization data provides more
information on potential biomarkers.
• Easily find and visualize interactions
of genes and proteins with specific
cell processes, diseases, and small
molecules
• Linkages with other Elsevier
products (Reaxys, PharmaPendium)
provide more information about
potential and observed biomarkers
Biomarkers are a critical early step in many discovery strategies

20. | 20
Drug repurposing
• Largest knowledgebase of drug
targets coupled with knowledge on
biology of more than 6000 diseases
provides the most information to
search for shared patterns
• Statistical enrichment analysis
simplifies identification of common
regulators and pathways
• Combine multiple disparate
pathways to create a comprehensive
picture of drug action in the context
of each disease, and better
understand off-target effects
Comprehensive pathways help identify alternative applications

21. | 21
NGS data interpretation
• Import, filter, and analyze VCF data,
as well as RNA-Seq data, from any
NGS platform
• Filter thousands of variations down
to a few important ones by
comparison to databases of
mutational information and predictive
tools
• The largest collection of literature-
derived molecular function data
enables more precise associations of
mutations with functional effects and
disease associations
Interpret gene mutations and gene expression information

22. Sample Pathway
Studio workflow

23. | 23
A blank canvas for your work
Starting out…

24. | 24
Working with search results…

25. | 25
Building a pathway…

26. | 26
Building a pathway…

27. | 27
Cleaning things up

28. Basic NGS
workflow

29. | 29
• Import and analyze NGS expression (RNA-Seq) data
• Browse the Database for specific variations
 Find a gene associated with a specific disease
 Find deleterious SNPs within a conserved coding sequence
• Analyze a single genotype sample
 Place affected genes into a new pathway
 Find pathogenic variants of a particular gene
• Analyzing multiple genotype samples
 Find mutations that differ between control and experimental groups
Support for the most common NGS analysis workflows

30. | 30
1. Import VCF file from disk or URL – await confirmation
Simple VCF file import

31. | 31
Once you have 1 or more VCF files loaded, you can
browse them for various features
Browse the mutation database for specific features

32. | 32
VCF files can also be searched for specific features
Search the database for mutations of interest

33. | 33
You can search for associations and functional impact
Easily identify mutations with probably negative impact

34. | 34
Compare data across multiple experimental and controls.
Filter by location, gene, disease, frequency, etc.
NGS workflows: compare multiple genotypes

35. Professional
Services Projects

36. | 36
Pathway Studio custom services engagements
Customized analyses, bespoke datasets/pathways can be performed
by our dedicated teams of PhD scientists
• Access to life science data and content with proven data curation, taxonomy
expertise, and semantic backbone across R&D and post market launch
• Demonstrated R&D data integration expertise
• Existing life science portfolio of solutions across development spectrum
• Global sales footprint in life science sector
Partnered with Pathway expert Dr. Phil Lorenzi
 Create an expert view on your area
 Compares across data types

37. • The Process: The Professional Services
team created a custom search in full-text
literature to find statements indicating
that the piece contained information
about protein mutations. This was then
integrated into a custom cartridge for
Pathway Studio.
• The Results: More than 100,000
mutations were found in the literature.
Using Pathway Studio, the customer can
search the list and find mutation they
needed — and the search strategies will
keep the their data set up-to-date.
37
Example: Custom data sets for targeted discovery
Challenge: Find all of the reported mutations in cancer cells.

38. Questions?