josé cruz toledo - aptamer basebc2012
Post on 19-Oct-2014
875 views
DESCRIPTION
Aptamer Base: A collaborative knowledge base to describe aptamers and SELEX experiments, by Cruz-Toledo, Jose; McKeague, Maureen; Zhang, Xueru; Giamberardino, Amanda; McConnell, Erin; Francis, Tariq; DeRosa, Maria; Dumontier, Michel. Presented at the 5th International Biocuration Conference, hosted by PIR in Washington, DC, April 2-4, 2012.TRANSCRIPT
Aptamer Base: A collaborative knowledgebase to describe aptamers and
SELEX experiments
Biocuration 2012 Tuesday April 3rd
Jose Cruz-Toledo
PhD candidate, Carleton University, Canada
1
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
2
PDBID: 1RAW
Aptamers offer several advantages over antibodies
• Entirely generated in vitro
• Can be selected to bind to specific targets
• Relatively low production cost
3
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– Out of date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
5
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
7
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
8
9
SELEX experimental details
10
Aptamer & target details
11
Aptamer Base data can be accessed in several ways
12
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"
}]
}]
13
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
14
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
15
Acknowledgements
Supervisors:
Dr. Michel Dumontier and Dr. Maria DeRosa
Collaborators:
Maureen Mckeague, Xueru Zhang, Amanda Giamberardino, Erin McConnell, Tariq Francis, Matthew Chan
16
Questions?
17