An introduction to Pathway Studio

Helping researchers understand the biology

of disease…

Frank White, PhD

May 27, 2015

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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

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Pathway Studio overview: Data, tools, visualization

Pathway Studio

Tools Knowledgebase

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

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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

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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

How can Pathway

Studio help you?

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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

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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…

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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…

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How does Pathway Studio help your research?

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Pathway Studio saves you time

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According to our customers…

Pathway Studio

versus similar tools

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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 PathwayStudio

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.

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

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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

Sample Pathway

Studio use cases

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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

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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

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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

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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

Sample Pathway

Studio workflow

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A blank canvas for your work

Starting out…

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Working with search results…

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Building a pathway…

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Building a pathway…

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Cleaning things up

Basic NGS

workflow

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• 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

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1. Import VCF file from disk or URL – await confirmation

Simple VCF file import

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Once you have 1 or more VCF files loaded, you can

browse them for various features

Browse the mutation database for specific features

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VCF files can also be searched for specific features

Search the database for mutations of interest

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You can search for associations and functional impact

Easily identify mutations with probably negative impact

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Compare data across multiple experimental and controls.

Filter by location, gene, disease, frequency, etc.

NGS workflows: compare multiple genotypes

Professional

Services Projects

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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

• 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.

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Example: Custom data sets for targeted discovery

Challenge: Find all of the reported mutations in cancer cells.

Questions?