TargetInsights: A New Method to Rapidly Access 'Specificity” of Selected Proteins' - webinar March...
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1 1 Your host: Ann-Marie Your presenter: Dr. Thomas van Himbergen Welcome to Elsevier Life Science webinar on Sandhoff Disease! We will begin soon.
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In drug discovery, a lot of energy is spent on researching disease specific proteins which may be suitable targets for drug intervention. TargetInsights helps you to dig out all the information which is hidden beneath the title and the abstract. Furthermore, Target Insights is a tool that helps you explore biological relationships in literature between concepts of interest. This webinar showed us how this is done.
Transcript of TargetInsights: A New Method to Rapidly Access 'Specificity” of Selected Proteins' - webinar March...
11
Your host: Ann-Marie Your presenter: Dr. Thomas van Himbergen
Welcome to Elsevier Life Science webinar on Sandhoff
Disease!
We will begin soon.
22
Elsevier’s Life Science Solutions
33
Webinar control panel:• ‘chat’ or ‘ask a question’ for question and comments•Option for full screen view
Q&A after presentation and demo
Useful tips
A New Method to Rapidly Access “Specificity” of Selected ProteinsWednesday, March 20, 2013 Thomas van Himbergen -- Project Manager
Profile Multiple proteins against Multiple diseases
Today’s Presentation
• General Introduction • Target Discovery • TargetInsights
• Use case: Sandhoff Disease • Basic Search: filtering searches• Advanced Search: relationship search• Multiple Search: disease protein profile
• Q&A and Demo
Good target selection is dependent on understanding disease & disease progression.
Pharmaceutical Target Discovery The First , Most Critical & Challenging Step
PIII/PIV PoCPI/IISafetyToxLead
ValLead
IDTarget
ValTarget
ID
Early Discovery
What proteins or
gene are associated
with disease of interest?
Is this target specific for disease x? Where else is
this protein expressed?
What is the function of this protein
target ?
Find new drug targets by:• Building & verifying disease models and
disease pathways
• Profiling proteins & genes against diseases and tissues and other biological properties to understand interactions
• Understanding functional relationships between entities and concepts to support target selection and disease mechanism hypotheses.
Good target selection is dependent on understanding disease & disease progression.
Pharmaceutical Target Discovery The First , Most Critical & Challenging Step
Validate drug targets by:• Finding evidence/ information on
proteins/genes to support experimental findings & hypotheses
• Uncovering information gaps – where data/ information is scarce or non-existing – to guide research
• Examining new information and how this affects selected projects to further support target selection decisions
Can this target be modulated or
alerted? If so what is best approach?
PIII/PIV PoCPI/IISafetyToxLead
ValLead
IDTarget
ValTarget
ID
Early Discovery
What assay or animal models
are best?
What types of experimental data has been published, siRNA,
genomic, knockout mice etc?
Can this target be modulated or
alerted? If so what is best approach?
PIII/PIV PoCPI/IISafetyToxLead
ValLead
IDTarget
ValTarget
ID
Early Discovery
Critical questions addressed!
What proteins or
gene are associated
with disease of interest?
Is this target specific for disease x? Where else is
this protein expressed?
What is the function of this protein
target ?
What assay or animal models
are best?
TargetInsights Search powerfully. Advance intelligently.
Full text relationship searching of biomedical literature, which is linked though a comprehensive taxonomy (thesaurus).
Full text annotations of the Elsevier and other publishers journals (approx. 600.000 articles/y in +5000 journals)
Additional annotations of Medline Unique Abstracts and Conference Abstracts (approx. 400.000/y)
Article in Press updates
Fully automated annotation.
Focus on genes/proteins, drugs and diseases.
TargetInsights Search powerfully. Advance intelligently.
Deep Indexing of Full-text Articles
9 target discovery relevant Taxonomy categories
Millions of terms aligned to taxonomies
Taxonomies and indexing
Sandhoff Disease Use-Case
• Rare genetic lipid storage disorder• Beta-hexosaminidase enzyme deficiency• Accumulation of lipids in the brain and other organs of
the body. • Progressive decline of the central nervous system.
• Classic Infantile Sandhoff is the most common form: characterized by little to no Hexosaminidase-A (Hex-A) and Hexosaminidase-B (Hex-B) enzyme activity.
• Search Question: What other proteins may play a role in the progression of this disease and may be useful drug targets to manage the disease symptoms?
Sandhoff Disease?
Streamline Search Strategy From disease to potential drug target
What other genes or proteins may play a role in the progression of Sandhoff disease and may be useful drug targets?
1. Basic Search: one concept at the document level ‘Sandhoff Disease’
1a. Select Known Biological functions- search
2. Advanced Search: co-occurrence search between concepts, sent level
Sandhoff Disease & cathepsin d
3. Multiple search – to determine if cathepsin d is specific to Sandhoff disease, profile multiple
diseases against protein class cathepsin.
1b. Select top protein(s) associated with biological functions- set up
co-occurrence
Basic Search at the Document Level
Search Results: 324 Hits
A Quick Comparison to PubMed:About 5 Times More Hits using TI…
63 hits versus 324. There is a lot of information overlooked in Title-Abstract searches!
Filter on Biological Function
Search Results: 182 Hits
Filter on Specific Genes or Proteins
Categories populated with each new search
Top 25 indexed terms within the search results are presented: Scale research intensity: higher in
list more research Narrow and refine search fast Examine relationships that may
have been overlooked
Protein of interest?
SD Enzymes
Results: Filter on Specific Genes or Proteins
Display: Abstract and Index Terms
Cathepsin D and Sandhoff Disease not mentioned in
Abstract
Search Method:
Co-occurrence Search
Co-occurrence Search: Doc, Paragraph, Sentence
Results: Doc, Paragraph, Sentence
Display: Abstract and Index TermsCathepsin D is not
mentioned in Title or Abstract.
Review Paper: Sandhoff disease and Cathepsin D
co-occur in the same sentence:
… over expression of Cathepsin D (CTSD) has been reported in the brain of murine models of
several other lysosomal diseases such as Gaucher’s disease, Sandhoff disease, GM1
gangliosidoses, Neimann-Pick A …
Search Method:
Multiple Co-occurrence Search
Browse the Dictionary or Search Direct
Browse
Search Direct
Profile Proteins against Disease• Assemble neurological diseases along one axis• Assemble Cathepsin protein family members along another axis• Build knowledge profile
Small body of evidence established discovery still probable
Potential emerging area of research, new hypotheses?
Matrix Search Results:
Review Resultsand
Read Papers
• Basic Search for ‘Sandhoff Disease’• Filtered results based on biological function: ‘Lysosomal
Enzyme’ and ‘Beta-hexosaminidase’• Reviewed the list of proteins found in the search results:
Cathepsin D
• Advanced Search: Co-Occurrence• Retrieved two papers describing a relationship between
‘Sandhoff Disease’ and ‘Cathepsin D’ based on sentence level co-occurrence)
• Set up multiple search:• Profile of the Cathepsin protein family against other
neurodegenerative diseases.
Summary of Findings
• Which search method to further explore in the live demonstration?• Basic Search • Co-Occurrence search• Multiple search matrix
User Poll
DEMO: www.targetinsights.com
Based on the results from the Poll:• Basic Search• Co-Occurrence• Multiple search
• TargetInsights is a powerful search tool that informs target discovery & validation approaches:• Leverages Elsevier’s world class full-text journals as well as
multiple publishers to create a best-in-class and unique content database
• Allows researchers to dig deep into full text articles for new & existing information to guide discovery & validation approaches
• Provides unique search formats that quickly summaries information to aid researchers in generating, refining and verifying target research hypotheses
Product Summary
Questions?
