1. The Ultralink – an expert system for contextual hyperlinking in knowledge management Manuel C. Peitsch Head of Systems Biology Novartis Institutes for Biomedical Research

2. 2 Ultralink/ M. Peitsch/ Bio-IT World April 2006 A Knowledge Space

3. 3 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Connecting the Knowledge Bodies (requirements)  Intelligent integration of heterogeneous data to enable “Seamless Navigation”:  One-stop shop.  Re-useable, in any Web and Office application.  Intelligent, i.e. knows about biology, medicine, chemistry, diseases, business, people, etc…  On demand and easy to use.  Configurable.

4. 4 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Connecting the Knowledge Bodies (Components)  Indexing of large heterogeneous data collections (databases, full texts) to enable semantic expansion.  Information Retrieval and Extraction, entity recognition, semantic enrichment.  Knowledge Map (navigating the conceptual network).  Terminology Hub (thesauri and ontologies).  Ontology-associated business rules.

5. 5 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Creating references (Terminology Hub) Different knowledge repositories have different ways to encode a concept:  Registry Number  Unique Internal ID  Concept Identifier  Enumerating terms  Just using different terms without any constraints Searching a term in source A and B may lead to different results although the underlying concepts exists in both sources (false negatives in IR and IE) Terminology Hub ensures coherent mapping  Between coding systems  Between different representation levels (e.g. ID vs. Concept)  Between local terms and global terms Over 8 GB of cross-referencing information

6. 6 Ultralink/ M. Peitsch/ Bio-IT World April 2006 What entities constitute our Terminology?  Chemical entities – IUPAC names, trivial names, trade names, INNs, compound codes, ligands.  Biological entities – targets, genes/protein, modes of actions…  Diseases, Indications, Side Effects, Contraindications  Institutions, Affiliations, People  Geographic locations  …

7. 7 Ultralink/ M. Peitsch/ Bio-IT World April 2006 The UltraLink : a revolutionary tool to navigate the “Knowledge Space”  Zoning  This process uses our (meta-) knowledge about information structure, and tags the relevant contexts of the documents or database records.  Identification of terms based on the terminology or on regular expression  Term Identification: identify the lexical items in a text, relate them to a term and retrieve the corresponding reference term via thesaurus relations.  Concept Identification: identify the concept related to the reference term(s).  Type Assignment: Assign the concept type related to a concept identifier  Extraction and normalization  Get list of rules to apply  Verifiers  Application of rules  Display

8. 8 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Creating the Ultralink

9. 9 Ultralink/ M. Peitsch/ Bio-IT World April 2006 UltraLink Examples Treatment of ambiguities WILMs TUMOR DISEASEWilms' tumor => nephroblastoma GENE NAMEWT1 TARGETWilms' tumor

10. 10 Ultralink/ M. Peitsch/ Bio-IT World April 2006 UltraLink Examples Term extraction / Normalization -> Examples (mtor, mammalian target of rapamycin)

11. 11 Ultralink/ M. Peitsch/ Bio-IT World April 2006 UltraLink Examples Term to UltraLink: granulocyte - macrophage colony stimulating factor Concept Type: TARGET Normalized term (non exhaustive): Granulocyte-macrophage colony-stimulating factor Synonyms: colony stimulating factor 2 Colony-stimulating factor, CSF,GCSF, GM-CSF Granulocyte macrophage colony stimulating factor Molgramostin, Sargramostim Local terms (non exhaustive list of examples): EMBL e.g. AC004511, AF373868, … Pubmed e.g. 1569568, 1737041, … NCBI e.g. 10090, 10116, 9606 GO e.g. GO:000512, GO:0019221, … UniProt e.g. P01587, …

12. 12 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Link to Pathway information from TCF7L2

13. 13 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Further query, Genome/Proteome Information

14. 14 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Access to tools and reagents

15. 15 Ultralink/ M. Peitsch/ Bio-IT World April 2006 MetaCore Map containing FZD4 (frizzled 4) Proteins where antibodies are available are marked with an additional icon Mouse-over shows specificity Hyperlink to Antibodies Web Report

16. 16 Ultralink/ M. Peitsch/ Bio-IT World April 2006 UltraLink Examples

17. 17 Ultralink/ M. Peitsch/ Bio-IT World April 2006 UltraLink Examples

18. 18 Ultralink/ M. Peitsch/ Bio-IT World April 2006 The Ultralink can be call from the Internet Explorer Internet Explorer Integration GPS Add-in Internet Explorer Integration GPS Add-in Web PageTagged Document 2 Sends the document for analysis 3 Gets back tagged parts 1 User requests for analysis 4 Injection of specific HTML tags Web Service (WSDL) GPS Lexical Analysis Server Tools Terminology Lexical Extraction Zoning Tagging DocStructures Meta-Rules

19. 19 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Activation UltraLink Annotations on any web page

20. 20 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Web Service (WSDL) The Ultralink is integrated with Microsoft Office Microsoft Smart Tag Extraction Microsoft Smart Tag Extraction Office DocumentTagged Document 2 Sends the document for analysis 3 Gets back tagged parts 1 User requests for analysis GPS Lexical Analysis Server Tools Terminology Lexical Extraction Zoning Tagging DocStructures Meta-Rules

21. 21 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Annotations on full text in a Word document

22. 22 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Ultralinks can be coded into any application

23. 23 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Acknowledgements Thérèse Vachon Martin Romacker Pierre Parisot Nicolas Grandjean Brigitte Charpiot Jean-Marc von Allmen Daniel Cronenberger Olivier Kreim

24. 24 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Knowledge Space and GPS Navigator Backup slides

25. 25 Ultralink/ M. Peitsch/ Bio-IT World April 2006 What constitutes the Knowledge Space Ultralinker Semantic Search Text Mining Analytics InternetOther Research Documentation ChemistryBiology Literature Comp. Inf.Bioinformatics Meta Data K map Thesaurii Ontologies Rules Defined workflows

26. 26 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Data Analysis – Protease modulators in CI DBs July 2004 - ADIS & Pharmaprojects Univariate - Companies Univariate - MOA Univariate - Diseases conditionned by Companies Clustering Diseases -MOAs

27. 27 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Graph Navigator – Protease modulators in CI DBs July 2004 - ADIS & Pharmaprojects

28. 28 Ultralink/ M. Peitsch/ Bio-IT World April 2006 Clustering