José Cruz Toledo - Aptamer basebc2012

Aptamer Base: A collaborative knowledgebase to describe aptamers and

SELEX experiments

Biocuration 2012 Tuesday April 3rd

Jose Cruz-Toledo

PhD candidate, Carleton University, Canada

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What are aptamers?

• In vitro selected short nucleic acid polymers that bind with high specificity and affinity to a variety of targets

– Small molecules, organic dyes, toxins, proteins and whole cells

– Binding affinities in the micro-nano molar range

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PDBID: 1RAW

Aptamers offer several advantages over antibodies

• Entirely generated in vitro

• Can be selected to bind to specific targets

• Relatively low production cost

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Aptamers are created using Systematic Evolution of Ligands by Exponential

Enrichment (SELEX)

4 Image source: http://bio349.biota.utoronto.ca/20069/bio349jerry1/images/background_fig2.jpg

Most of our knowledge about aptamers is still found only in scientific publications

• There are only a few existing aptamer databases

– Out of date

– Cannot be updated by users

– Data is not available for download

– Data cannot be queried directly

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Freebase is a community created knowledge base

• Data in Freebase is stored as a structured graph containing over 22 million topics

• Metaweb Query Language (MQL) is used for querying

• Topics are organized into bases

6 http://www.freebase.com

The Aptamer Base is a hub for aptamer knowledge, built on Freebase

• A collection of experimental details about SELEX based experiments

• Over 5700 topics about experimental details of ~250 SELEX experiments

• Details for over 1200 aptamers including sequences, dissociation constants and secondary structure predictions

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Type # Instances

Experimental outcome 1903

Linear polymer 1629

Interactor 1582

Nucleic acid 1549

Aptamer 1239

Interaction 1068

RNA 1006

Dissociation constant 896

Pairwise interaction 889

Experiment 641

The Aptamer Base facilitates collaborative data contribution and sharing

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SELEX experimental details

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Aptamer & target details

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Aptamer Base data can be accessed in several ways

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aptamer.freebase.com

freebase.com/labs/parallax/

aptamerbase.semanticscience.org

MQL allows powerful querying over the Aptamer Base

How many SELEX experiments are described in the Aptamer Base?

[{

"type": "/base/aptamer/selex_experiment",

"return": "count"

}]

Provide a list of all interactions that have as participants RNA aptamers

[{

"id": null,

"type": "/base/aptamer/interaction",

"has_participant": [{

"id": null,

"a:type": "/base/aptamer/aptamer",

"b:type": "/base/aptamer/rna"

}]

}]

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Find all affinity experiments that dispute interactions that have as participant “Sulforhodamine b”

[{

"mid": null,

"type": "/base/aptamer/affinity_experiment",

"disputes": [{

"type": "/base/aptamer/interaction",

"has_participant": [{

"type": "/base/aptamer/molecule",

"name": "Sulforhodamine b"

}]

}]

}]

Find all dissociation constants that have a value that is less than 1E-6 for interactions involving either L-Arginine or Thrombin [{

"mid": null,

"type": "/base/aptamer/dissociation_constant",

"has_value<": 0.000001,

"/base/aptamer/dissociation_constant/is_dissociation_constant_of": [{

"/base/aptamer/interaction/has_participant": [{

"mid": null,

"type": "/base/aptamer/aptamer_target",

"name|=": [

"L-Arginine",

"Thrombin"

]

}]

}]

}]

Results: http://tinyurl.com/d3ox66m

Results: http://tinyurl.com/cckdax7

Results: http://tinyurl.com/bmcyfdw

Results: http://tinyurl.com/c8ystcg

The Aptamer Base is not just another Aptamer Database

• The Aptamer Base is the only collaborative aptamer resource on the web

• Users are not limited to an HTML form for accessing data – TSV :

http://download.freebase.com/datadumps/latest/browse/base/aptamer/

– RDF: http://rdf.freebase.com/rdf/[TOPIC_ID]

– Powerful query language: http://wiki.freebase.com/wiki/MQL

• The aptamer Base extends over ~2700 pre-existing topics on Freebase

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Future Work

• Implement a topic entry interface at http://aptamerbase.semanticscience.org

• Add SELEX based aptamer journal articles published between 2010 and 2012

• Integrate data with the Bio2RDF network

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Acknowledgements

Supervisors:

Dr. Michel Dumontier and Dr. Maria DeRosa

Collaborators:

Maureen Mckeague, Xueru Zhang, Amanda Giamberardino, Erin McConnell, Tariq Francis, Matthew Chan

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Questions?

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