Transcript Interpretation of microarray expression data using

Interpretation of microarray
expression data using
ontology browsing
Meeting the needs of a new era
Anders Bresell
17/07/2015
Presentation of Master Thesis
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Motivation
After we have preformed a microarray
analysis we have a set of interesting genes
that we want to know more about.
The existing knowledge are found in
articles and databases. But we need a lot
of time to skim through the information to
get a hunch of what the knowledge is
about.
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Motivation
In order to get a first glance of what
knowledge we have about a set of genes.
We need to find a way to represent the
knowledge in a more condensed way.
For this we used Ontologies.
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What is an Ontology?
Definition:
An explicit specification of
conceptualisation [Gruber 93]
A controlled vocabulary that has
specified relationships between the
terms.
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Why is an ontology so nice?
• It provides a common language of a
domain for human agents.
• It gives a inter-operability between
computer systems.
• It enables an improvement of the
search and knowledge acquisition
process.
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Example of an Ontology
Biological Process
Cell communication
Response to external stimulus
DNA protection
Cell growth and maintenance
Metabolism
Nucleotide metabolism
DNA metabolism
DNA protection
Stress response
DNA protection
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Ontology 4
Existing Ontologies
MeSH
All published litterature is indexed by
the terms from MeSH.
Gene Ontology
Organism independent ontology
describing Molecular function, Biological
process and Cellular component.
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Information
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Annotation
Article (in Medline)
GENE
Term 1
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Solution
• Instead of having the information in the
form of articles and databases we
represent it as a set of keywords or
terms.
• By using ontologies we could specify or
generalise the terms.
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Ontology Annotation Tree browser (OAT)
• We built a tool
– Database (holding the annotations and the
tree structure of the ontology)
– Tree Browser tool (Visualises the
ontology)
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The OAT-tool
Checkbox for terms
which are to be
included in the
report
Significance of the
Annotation
Number of genes
annotated with this
term
Number
of genes
below
Number of annotations below
Link to MeSH description
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Report feature
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Summary of OAT 1
• Only terms that are relevant for the
genes are displayed.
• This tool only aims to give some brief
information about a group of genes.
• The set of genes must undergo further
studies. The report page directs us to
the articles we used as source when we
made the annotations.
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Limitations of OAT
• The OAT-tool is totally dependent on the
annotations. If we have no connections
between a gene and a term, the tool
would not tell us anything about the
gene.
• We will import more annotations during
this summer. Then the tool will be a big
help in the digestion of information.
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More Annotations
• GeneOntology
– GOA (Swissprot, TrEMBL, Interpro etc.)
High quality
– Compugene
Unsupervised!!
• MeSH
– Human Protein (Swissprot, OMIM)
Text Mining by Ian Dix et al.
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Modifications
• Change of DBMS from Berkeley DB to
MySQL.
– To many annotations.
– To process demanding calculation due to
the inflexible querying of data.
– Other systems could use the data.
– Makes the updating of data easy.
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Feedback
Give me feedback…
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Acknowledgement
•
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Patrick Lambrix
Bo Servenius
Per Broberg
Thomas Breslin
Tobias Fändriks
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