Euretos presentation ACS


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Presentation held at the ACS convention in San Francisco on August 11, 2014

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  • 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

  • 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.
  • Euretos presentation ACS

    1. 1. Beyond Text Mining: BRAIN August 11th, 2014/ACS
    2. 2. 2 Market Drivers Euretos BRAIN Use cases Close Topics
    3. 3. The Data Tsunami Datarrhoeia Standards? Needle Transport DIY Data Key drivers 3Copyright Euretos b.v. 2014
    4. 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
    5. 5. Is anyone really ‘doing it’? 5Copyright Euretos b.v. 2014
    6. 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
    7. 7. Market Drivers Euretos BRAIN Use cases Close Topics 7Copyright Euretos b.v. 2014
    8. 8. Addressing researchers’ needs 8Copyright Euretos b.v. 2014
    9. 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. 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. 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
    12. 12. Market Drivers Euretos BRAIN Use cases Close Topics 12Copyright Euretos b.v. 2014
    13. 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
    14. 14. SEEING THROUGH DATA Connected Is in PMID: 22869380 PMID: 20164304 PMID: 22869380 beta parvin Akt1 Binds PMID: 20164304 paxilin Leucine aspartic repeat motifs 14Copyright Euretos b.v. 2014
    15. 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. 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
    17. 17. Market Drivers Euretos BRAIN Use cases – Time to knowledge Close Topics 17Copyright Euretos b.v. 2014
    18. 18. Based on meticulous reading of 221 articles Time to knowledge 18Copyright Euretos b.v. 2014
    19. 19. Using BRAIN Path predictor function 19Copyright Euretos b.v. 2014
    20. 20. Using BRAIN Shortest Path function 20Copyright Euretos b.v. 2014
    21. 21. Detail statement and provenance Not mentioned in the Miedema paper. 21Copyright Euretos b.v. 2014
    22. 22. Significant Time-to-Knowledge saving 4 minutes….in BRAINReading 221 papers: WEEKS 22Copyright Euretos b.v. 2014
    23. 23. Market Drivers Euretos BRAIN Use cases – Knowledge Prediction Close Topics 23Copyright Euretos b.v. 2014
    24. 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. 25. Store terms and statements in project folder 5Copyright Euretos b.v. 2014  
    26. 26. Select statements with relevant relations 6Copyright Euretos b.v. 2014
    27. 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
    28. 28. Market Drivers Euretos BRAIN Use cases – Target dossier Close Topics 28Copyright Euretos b.v. 2014
    29. 29. P14735 One click target dossiers 29Copyright Euretos b.v. 2014 We provide • Target dossiers for target owners and internal review panel Reports Overview • Based in Leiden, NL • Bayer, Lundbeck, Merck, AstraZeneca, Janssen, Sanofi, UCB Consortium • Target screening Key functions  Target – disease association (predict function)  Drugability analysis of a compound  Indepth compound analysis ranked by QeD
    30. 30. 30Copyright Euretos b.v. 2014
    31. 31. 31Copyright Euretos b.v. 2014
    32. 32. Market Drivers Euretos BRAIN Use cases – Adverse Drug Reaction Close Topics 32Copyright Euretos b.v. 2014
    33. 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.
    34. 34. Connect the key concepts 34Copyright Euretos b.v. 2014
    35. 35. Review the evidence 2006 2010 2008 35Copyright Euretos b.v. 2014
    36. 36. Market Drivers Euretos BRAIN Use cases Close Topics 36Copyright Euretos b.v. 2014