Transcript Asymmetries in Retrieval of Gene Function Information

Asymmetries in Retrieval of
Gene Function Information
Timothy B. Patrick, PhD1,
Lillian C. Folk, MS2,
Catherine K. Craven, MLS3
1Healthcare
Administration and Informatics, University of Wisconsin-Milwaukee
2College Of Veterinary Medicine, 3Health Management and Informatics,
University of Missouri-Columbia
Acknowledgements
• 2004 Donald A. B. Lindberg Research
Fellowship
• University of Missouri National Library of
Medicine Biomedical and Health
Informatics Research Training grant
Overview
• Background
– What is an asymmetry in retrieval of gene function
information?
• Life science information retrieval and processing workflows
• Example of asymmetrical workflows
– Compare three apparently equivalent asymmetrical
workflows
• Conclusion
– Documentation standards
– Multidisciplinary teams for life science workflows
What is an Asymmetry in Retrieval?
• Taking different paths to get the same kind
of information about a given biological
object
• Life science information retrieval and
processing workflows
Complex Information Retrieval
• May involve the use of multiple information
resources databases and analysis tools, in
combination
• Such combinations of resources are often
represented as workflows.
Workflow Standards
• Business Process Execution Language for
Web Services Version 1.1
– http://www-128.ibm.com/developerworks/library/specification/ws-bpel/
• Simple Conceptual Unified Flow Language
(SCUFL)
– Taverna Workbench
• http://taverna.sourceforge.net/
Logical Workflows
• A logical workflow is sort of like a logical
process model, with processes, data links,
and control links
• Key aspects of the workflow are inputs,
outputs and processes that transform the
data
Sequence
ID
get DNA
sequence
Sequence
string
Similarity
search
results
Physical Workflows
• A physical workflow is like a physical
process model, with processes, data links,
and control links
UI
fetch DNA
sequence
Sequence
string
BLAST
BLAST
results
Physical Workflow
Antoon Goderis, Ulrike Sattler and Carole Goble, Applying DLs to workflow
reuse and repurposing Description Logics workshop, Edinburgh, Scotland, 2426 July 2005
Asymmetry
• Asymmetry means the paths or workflows
are different: from the same set of
potential inputs about some biological
object they take different paths to produce
the same kind of results.
• Asymmetrical workflows are equivalent if
they do produce the same results.
This Study
• Example of asymmetrical workflows that
might look to a user to be equivalent but
which are not equivalent due to various
features of the resources involved.
• Knowledge that they are not equivalent
requires knowledge of metadata about the
resources.
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Affymetrix
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
http://www.affymetrix.com/corporate/media/genechip_essentials/gene_expression/Features_and_probes.affx
http://www.mygrid.org.uk/images/pagemaster/GravesDiseasescenario_1.png
http://www.mygrid.org.uk/images/pagemaster/GravesDiseasescenario_1.png
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Methods
•
We first collected representative DNA Accession numbers associated with
genes expressed in a microarray experiment designed to identify changes
in gene expression associated with skeletal muscle recovery from
immobilization-induced sarcopenia. This experiment sought, using a mouse
model, to identify differences in gene expression associated with successful
recovery from sarcopenia in young muscle as compared to failed recovery
in old muscle.
– NIH grant AG18881
• Pattison JS, Folk LC, Madsen RW, Childs TE, Booth FW. Transcriptional profiling
identifies extensive downregulation of extracellular matrix gene expression in
sarcopenic rat soleus muscle. Physiological Genomics 15(1):34-43, 2003.
• Pattison JS, Folk LC, Madsen RW, Booth FW. Selected Contribution: Identification of
differentially expressed genes between young and old rat soleus muscle during
recovery from immobilization-induced atrophy. Journal of Applied Physiology
95(5):2171-9, 2003.
• Pattison JS, Folk LC, Madsen RW, Childs TE, Spangenburg EE, Booth FW. Expression
profiling identifies dysregulation of myosin heavy chains IIb and IIx during limb
immobilization in the soleus muscles of old rats. Journal of Physiology 553(Pt 2):35768, 2003.
Methods
• Next, we retrieved the Unique Identifiers (UI’s) of
Entrez Pubmed citations that were associated
with the Accession numbers by each of the three
Entrez resources.
– Directly in the case of Entrez Pubmed
– Indirectly, via Pubmed links in the case of Entrez
Nucleotide and Entrez Gene
• Next, we compared the number of Pubmed ID's
retrieved by the three resources for each of the
Accession numbers.
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Three Workflows
Affymetrix
Affymetrix
Genbank
Accession
number
Genbank
Accession
number
Nucleotide
Pubmed links
Affymetrix
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
Summary of Pubmed ID’s by
Accession Number
# of
Pubmed
ID’s
# of
Pubmed
ID’s
# of
Accession
numbers
# of
Accession
numbers
# of
Pubmed
ID’s
# of
Accession
numbers
0
198
0
132
0
216
1
36
1
112
1
34
2
10
2
5
2
0
3
4
3
2
3
1
4
1
4
0
4
0
5
2
5
0
5
0
Total
251
Pubmed
Total
251
Nucleotide
Total
251
Gene
Methods
• Compared number of Pubmed ID’s
produced for each Accession number by
each workflow.
• Applied non-parametric test: Kendall’s W
– Pubmed versus Nucleotide versus Gene
– p < .05
The Three Workflows Are Not
Equivalent
Affymetrix
Genbank
Accession
number
Affymetrix
≠
Affymetrix
Genbank
Accession
number
Nucleotide
≠
Pubmed links
Genbank
Accession
number
Gene
Pubmed links
Pubmed
Pubmed
Pubmed
Pubmed ID
Pubmed ID
Pubmed ID
The SI field identifies secondary source databanks and accession numbers
of outside resources discussed in MEDLINE articles. The field is composed
of the source followed by a slash followed by an accession number and can
be searched with one or both components, e.g., genbank [si], AF001892
[si], genbank/AF001892 [si].
The SI field and the Entrez sequence database links are not linked.
The PubMed links to these databases are created from the reference
field of the GenBank or GenPept flat file. These references include
citations that discuss the specific sequence presented in these flat
files.
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=helppubmed.box.pubmedhelp.Box_1_Search_Field_
D#pubmedhelp.Secondary_Source_ID_
Conclusions
Need for Documentation
• The first conclusion I take from this project
is that there is a need for documentation of
workflow details.
– In another study we look at the character of
documentation of information processing and
retrieval methods in published reports of
microarray experiments
Multidisciplinary Teams for
Workflows
• The second conclusion I take is that the
development of workflows requires
multidisciplinary teams.
KNOWLEDGE-ENABLED WORKFLOWS
METADATA
TOOLS
INFORMATION ITEMS
KNOWLEDGE-ENABLED WORKFLOWS
METADATA
TOOLS
INFORMATION ITEMS
domain
expert
(scientist)
KNOWLEDGE-ENABLED WORKFLOWS
METADATA
domain metadata
expert
(information
specialist)
TOOLS
INFORMATION ITEMS
domain
expert
(scientist)
KNOWLEDGE-ENABLED WORKFLOWS
METADATA
domain metadata
expert
(information
specialist)
TOOLS
INFORMATION ITEMS
domain
expert
(scientist)
workflows