4. 4
* 2013: Ann Winblad
legendary investor and senior partner at Hummer-Winblad
“Data is just like crude.
It’s valuable, but if
unrefined it cannot
really be used. It has to
be changed into gas,
plastic, chemicals, etc.,
to create a valuable
entity that drives
profitable activity.”
Data: The new oil
6. Life sciences – the perfect storm?
Phenome
Metabolome
Transciptome
Proteome
Genome
The easy ‘low hanging fruit’ medical
discoveries have been made
New ‘higher hanging fruit’ research
is orders of magnitude more
complex
Drowning in data
1.5 new article published every minute
Massive multi-omics output data (genome
data alone doubles per 8 months)
Lost in data
Many databases are consulted daily
Each only have a fragment of the puzzle
Each have specific classifications, terms
Google as the only integrative tool
6Copyright Euretos b.v. 2014
9. Many online resources
Look through data
Discover new relations
Instantly evaluate evidence
Personalise alerts
Minimise Time to knowledge
Euretos Product Solution:
9Copyright Euretos b.v. 2014
10. Products & Services
10Copyright Euretos b.v. 2014
KaaS
Overview
• Knowledge as a Service
• User friendly application
• Instant access
• Public & private data
• Secure
• Up to date
• Easy collaboration
• Alerts
Private Instance
Overview
• On-site BRAIN install
• Behind own firewall
• Public & private data
• Frequent updates
• Tailored pricing
• Full integration into local
environment
Reports
Overview
• Standard reports
• Custom reports
API
Overview
• Access to BRAIN database
• Develop own applications
License
• Fixed price per report /
• Subscription
License
• Monthly subscription
• Integration services
License
• Annual base license &
• Per transaction fee
License
• Annual base license &
• Support fee &
• Professional services
11. Selected references
11Copyright Euretos b.v. 2014
We provide
• BRAIN KaaS to the pre-
clinical research team
We provide
• Target dossiers for target
owners and internal
review panel
We provide
• API for in-house solution
development including
project support
We provide
• In-house installation of
key elements of BRAIN to
support data indexing &
publishing
KaaS
Overview
• HQ Kopenhagen, DK
• Listed company
• Development of human
antibody therapeutics for
cancer treatment
Private Instance
Overview
• HQ Hinxston, UK
• Official EU infrastructure
for life sciences data
• ‘FAIR’ datapublishing of
public research data
Reports
Overview
• Based in Leiden, NL
• Bayer, Lundbeck, Merck,
AstraZeneca, Janssen,
Sanofi, UCB Consortium
• Target screening
API
Overview
• HQ San Diego, US
• Agricultural, industrial
and healthcare markets
• Plant and yeast genetics
& trait development
13. A STATEMENT: [Term A - relates to - Term B] & it’s SOURCE
R. Yamaguchi, 2008,
Journal of Systems
Biology
Term ‘A’
KLK2 gene
‘relates to’
Causes
Term ‘B’
Prostate Cancer
Source
BRAIN knowledge refinery process
We refine data to the smallest unit of knowledge (a Nanopublication)
Disambiguation – By knowing all terms, their synonyms and storing
them as a single concept. Whatever term you enter, we always find what
you mean
Look through data – By connecting these Nanopublications and thus
‘look through’ all the data sources at once
Data reduction – By taking only Nanopublications from raw data and ‘zip
up’ all identical ones in a single ‘Cardinal Assertion’.
Performance – the result: high performance at a very low footprint
13Copyright Euretos b.v. 2014
15. Biological
pathways
Genetics
Proteins
Phenotypes
Chemical/
Pharmacology
Other
H1 2014 H2 2014
Pubmed
Uniprot
ChEMBL
EntrezGene
WikiPW
Drugbank
Enzyme
Protein Data
bank
Genes /
Diseases
Reactome
LOVD
ENCODE
SNP db
HMDB
GWAS Jaspar DB
Tiger
Epigenomics
Secreted
Protein db
Binding
db
DBGaP
BioGRID
SuperLigandsPubChem
NCIClinicaltrial USPTO
Gene
Ontology
Protein
Atlas
CTD
H1 2015
KEGG
Foodb
TD3B
NCI/UMLS
Comprehensive
15Copyright Euretos b.v. 2014
16. In summary: Value to the researcher
First to Knowledge…
Create a single view on private &
public data
See all existing knowledge in all
sources at once
Discover ‘potential’ relations
Collaborate on specific hypotheses
Keep up to date via alerts
….First to Market
Find more leads for research
Increase quality of research
Decrease late stage attrition of
leads
Accelerate end to end development
process
Save time, cost & money
16Copyright Euretos b.v. 2014
24. “Also just saw this
article on ALS and
Retigabine, a drug that
affects Potassium
channels and might
work for ALS.
Would BRAIN have
predicted this
relationship?
4Copyright Euretos b.v. 2014
Knowledge prediction
25. Store terms and statements in project folder
5Copyright Euretos b.v. 2014
27. Before this paper
was published,
BRAIN contained
sufficient indirect
relationships
between
Retigabine and
ALS to predict it as
a potential drug.
7Copyright Euretos b.v. 2014
Discovery that several mutations associated with ALS cause abnormally high activity in motor neurons > early degradation. There is a deficit
in open potassium channels in ALS motor neurons. Retigabine, a drug that opens potassium channels and approved for human use, seems
to normalize ALS cells in vitro, reducing their hyperexcitability > clinical trials in preparation.
Then visualize statements
Location
of
Causes
Stimulate
s
Interacts with
Causes
Associated with
Location
of
Stimulate
s
Location of
Stimulates
Stimulates
Interacts with Causes
Causes
Location of
Affects
33. Adverse drug reaction assessment
33Copyright Euretos b.v. 2013
Rosiglitazone (trade name Avandia,
GlaxoSmithKline) is an antidiabetic
drug in the thiazolidinedione class
of drugs.
A meta-analysis of 16 observational studies released in
March, 2011, provides evidence that rosiglitazone is
associated with a higher risk of heart failure,
myocardial infarction and death than a similar agent,
pioglitazone in real life.
When you look for direct statements between ALS and potassium channels there is no direct relationship but if you use the BRAIN shortest route function several hundreds of indirect relationships are found. I have added the most relevant ones to my knowledge lab and….
Selected several with relevant relations
Once you visualize them it is shown that ALS and potassium channels are indeed related through regitabine (the drug mentioned in the article
Default starting point.
Find individual terms and use as starting point for:
exploring based on CATEGORIES
Finding relations based on 2nd KEYWORD
In the search panel, the CATEGORY buttons are filters for the result display page.
Top hits is the Top x rank based on number of statements. Top hits is default. If another option is selected, top hits is deselected.
Navigate from here:
Click term - > Relate to categories [screen 2]
Detail -> Keyword detail [screen 3]
Relate other keyword [screen4]
- Generate KEYWORD REPORT (if available for the semantic group/type)
Add KEYWORD to Workspace for notifications
NEW KEYWORD SEARCH
Well known case of Avandia. In 2011 a study was published indicating rosiglitazone was associated with a higher risk of myocardial infarction
When using the BRAIN shortest route feature (looking at indirect relationships between the two concepts involved many genes show up where the chemical stimulates higher expression which induces myocardial infarction. The relationship is so strong in the knowledge graph that the compound and the disease are almost pushed onto each other! For all realtionships (statements, triples) found one can review the underlying articles for evidence
Which shows that way before the 2011 study the relationship found was a known fact. This approach can be used to determine possible adverse effects of a compound and is actually also used in use case 1 I showed before.