CD40 ligand and tumor necrosis factor alpha, the cells acquire a mature phenotype of dendritic cells that is characterized by up-regulation of human leukocy

te antigen (CD80, CD86, CD40and CD54 and appearance of CD83. These

Second Order Semantic Enrichmentand the role of Wiki’s for Professionals

Second Order Semantic Enrichmentand the role of Wiki’s for Professionals

•Peter Bram ‘t Hoen•Ellen Sterrenburg•Herman van Haagen•Allessandro Botelho-Bovo•Judith Boer•Johan den Dunnen •Gert Jan van Ommen

•Peter Bram ‘t Hoen•Ellen Sterrenburg•Herman van Haagen•Allessandro Botelho-Bovo•Judith Boer•Johan den Dunnen •Gert Jan van Ommen

•Erik van Mulligen•Martijn Schuemie•Rob Jelier•Antoine Velthoven•Christina Hettne•Jan Kors•Johan van der Lei

•Erik van Mulligen•Martijn Schuemie•Rob Jelier•Antoine Velthoven•Christina Hettne•Jan Kors•Johan van der Lei

•Christine Chichester•Erik van Mulligen•Marc Weeber•Kevin Kalupsen•Reuben Christie•Jacintha van Beemen•Nickolas Barris•Albert Mons

•Christine Chichester•Erik van Mulligen•Marc Weeber•Kevin Kalupsen•Reuben Christie•Jacintha van Beemen•Nickolas Barris•Albert Mons

•Gerard Meijssen•Erik Moeller•Peter Jan Roes•Karsten Uil•Siebrand Mazeland•Sabine Cretella

•Gerard Meijssen•Erik Moeller•Peter Jan Roes•Karsten Uil•Siebrand Mazeland•Sabine Cretella

Barend MonsBarend Mons

The ConsortiumOpen Access Semantic Support Technology

For on-line Knowledge Tracking, Discovery and Management

WikiProfessional

Semantic Web workspaces for scientistsenabling real time knowledge exchange and

exploration

Many challenges in current bomedical research

• Volume of data (both high troughput and text)• Complexity • Distributed systems and databases• Incompatible data formats• Multi-disciplinarity• Multi-linguality• Ambiguity of terminology• Inability to share Knowledge• Globalization of knowledge

•Repetition of facts is of great value for the readability of individual papers, •but the fact itself is a single unit of information, and needs no repetition.

– A defining characteristic of wiki technology is the ease with which pages can be created and updated. Generally, there is no review before modifications are accepted.

The Million Minds Approach

Personal Communication Johan den Dunnen.Personal Communication Johan den Dunnen.

Websites such as www.dmd.nl are increasingly cited in the literatureWebsites such as www.dmd.nl are increasingly cited in the literature

0

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1 researchgroup

2 or moregroups

genes/proteins

The majority of (SP) proteins has more than 1 research group asociatedThe majority of (SP) proteins has more than 1 research group asociated

So…..can we use wikis for this ??????So…..can we use wikis for this ??????

• Contextual annotation of web pages for interactive browsing, van Mulligen E, Diwersy M, Schijvenaars B, Weeber M, van der Eijk CC, Jelier R, Schuemie M, Kors J, Mons B, Medinfo 2004, 11:94-8• Which gene did you mean?, Mons B, BMC Bioinformatics 2005 Jun 7, 6:142

First order semantic enrichment

The Knowlet

2nd order S.E.

<Source concept><Target Concept><Relations>:

<Typea1> Database facts (mutiple attributes)<Typea2> Community Annotations (WikiProf)<Typeb1> Co-occurrence sentence<Typeb2> Co-occurrence abstract<Typec1> Concept Profile Match<Type c2> Sequence similarity (BLAST score Genes and Proteins only)<Type c3 Co-expression with (genes from expression Databases)

Knowlet building block

Knowlet of core concept Knowlet space

What does a Knowlet look like ‘under the hood’?

KKKK DDDD

KKKK GGGG

KKKK HHHH

KKKK ZZZZ

KKKK BBBB

KKKK EEEE

KKKK AAAA

KKKK DDDD

KKKK FFFF

KKKK IIII

KKKK DDDD

KKKK GGGG

KKKK HHHH

KKKK ZZZZ

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factual associativeco occurrence

• Rules to combine different sources of information into a single relationship

• Time-stamped information• The relationship to the original texts or

database entries

• A Knowlet represents a unit of thought interconnected with other units of thoughts or in other words: a ‘cloud’ of concepts that have one or more relationship types with the central (selected) concept

• The interconnection reflects a semantic relationship derived:

– From facts in database– From co-occurrence in a text– From other associations

• Relations have a strength– Based on the source of relationship– Based on the amount of «evidence»

• Knowlets belong to one or more semantic classes: proteins, diseases, authors, organizations, journals, experiments, etc.

• Each Knowlet is uniquely identified by a URL or URI (Unique Resource Identifier)

The Knowlet

person organisation Object 1

gene

Object 2

disease

Object 3

drug

3. Building an association matrix of large data sources

1 Million

1 Million

Function unknow nChaperonesChromatin structureFibrous proteinsmRNA metabolismOthersRibosomal proteinsRibosome biogenesisTranslation

SRPPARN

l

• Assignment of protein function and discovery of new nucleolar proteins based on automatic analysis of MEDLINE. Martijn Schuemie, Christine Chichester, Frederique Lisaceck, Yohann Coute, Peter-Jan Roes, Jean Charles Sanchez, Barend MonsSpecial issue on Systems Biology in Proteomics, 2008 (accepted for publication)

Cluster studies on basis of Homologene IDs

Cluster 4: EOM-specific genes in mdx

Cluster 5: Development of EOM muscleand rat atrophy

Cluster 1:Mdx miceDysferlin-deficient mice

Cluster 2: myositisCluster 3: DMD

GeneSet Clusterer, Rob Jelier, Erasmus MC

Kappa-based clustering based on Gene ID

Clustering of genes based on similarity of concept profiles

GeneSet Clusterer, Rob Jelier, Erasmus MC

Cluster 1: atrophy and myopathy

Cluster 2: extraocular muscle of mdx

Cluster 3: human and mouse muscular dystrophies and myositis

Cluster 4: long gene lists

Cluster 5: muscle differentiation;Ky-mutant and Fxr-/- mice

Cluster 6: ageing and sarcopenia

Evaluate biological processes that bring studies together

DatasetComparer, Rob Jelier, Erasmus MC

No overlap on GeneID level

Many assocations on concept profile level

Annotate

• OmegaWiki (terminology system)• Wiki Authors• Wiki Medical/Clinical• Wiki Proteins• Wiki Chemicals• Wiki Etc.

Allow for:

• Community Annotation• Quick growth of terminology systems• Semantic Linking between concepts

Knowlet 

Association Matrix Meta-analysis

Expert Challenge

WikiZ/PExpert comments

Peer to Peer Review

Final Approval

U.W. Fingerprint

Update

Literature

Protein A

0.1

0.4

0.9

New publications or annotations

Solid (a)

Liquid (b)

Gas (C)

1st order Semantic enrichment

ReductionFalse Positives

DiscussionVoting in Wiki

Meta-analysisProximity measures

Proposals to Data bases ?

Central Annotation

• REGISTRATION (1X)

• Unique Author ID• E-mail Adress• PHP/userpage• People Knowlets

• Unique concept ID• Language variants• Homonyms• Definitions (brief)• Object Knowlets

Science Wiki’s• UID from WiktionaryZ• Research information• Talk-page• Liquid Threads• Object Knowlets

• UID from WiktionaryZ• Articles about UID’s• Encyclopaedic/ NPOV• Anonymous allowed

Nature News February 15, 2007

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Step 2: select concepts of interest

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v chloroquineprimaquine

Para-amino-benzoic acidNew Drug ????

Cellular Memberan (GO)Mosquitoes

Core concept: Malaria (mean distance 5)

Semantic distance to: Malaria

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Plasmodium Chabaudi

F+, C+, A+

F-, C+, A +

F-, C-, A+

The Knowlet Visualization

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Mosquitoes

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Core concept: Malaria (mean distance 5)

Para-amino-benzoic acidCellular Memberan (GO)