Transcript Molecular Interaction Maps - National Alliance for Medical Image

Creating a DBP Community to Enhance the
NCBC Biomedical Impact
NCBC Work Group Report, 18 July 2006
MAGNet Center: Andrea Califano
NCIBI: Brian Athey
Simbios: Russ Altman
Workgroup Goals
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Problem: The NCBCs have no workgroup to help build the DBP community
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Goal 1: To determine the Mission and Goals for the Applications of Systems Biology,
Modeling and Analysis Working Group
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Goal 2: To determine how this group would interact with the 2 other NCBC Working
Groups to define key sets of:
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Data
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Tools
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Methodologies
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Ontologies
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DBPs
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Goal 3: Identify NCBC DBPs that are highly motivated to participate in the Working
Group
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Goal 4: How to link to external communities (e.g., DREAM-like activities)?
Additionally: Discuss as a focused example “Molecular Interaction Maps” in the context of
the DBPs
DBP Success Depends on the Availability of an Integrated
Resourceome (Not a priority for Core I/Core II Projects)
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Integrated Computational Biology Platform
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Support for gene expression data, physicsbased simulations, image analysis,
sequences, pathways, structure, etc. (40+
visualization and analysis modules).
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Access to local and remote data sources
and analytical services.
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Support for workflow scripting.
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Integration with grid infrastructures.
Development framework
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Open source development.
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Modular/extensible architecture, supporting
pluggable components with configurable
user interface.
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Easy integration of 3rd party components.
The integration process
must be driven by the DPB
requirements rather than
by Core I/II activities.
We Must Work With the “Yellow Pages” WG to Assemble
an Indexable List of Most Useful Tools and Platforms
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Many Toolkit and platforms
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Internal
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External
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SimTk
Genopia
VTK/ITK
Brainsuite
geWorkbench
GenePattern
MiMI
SAGA
miBLAST
MarkerInfoFinder
GenePattern
Systems Biology Workbench
myGRID
Cytoscape and ISB tools
How do we make these tools interoperable? This must be DBP-driven because
other cores (I/II) do not necessarily depend on tool interoperability.
GenePattern/geWorkbench Interoperability:
An Opportunity and a Starting Point
Execute GenePattern
modules from within
geWorkbench
KNN
PCA
WV
GSEA
SVM
ARACNE
SOM
SPLASH
GenePattern Module
Repository
Wrap geWorkbench
modules as
GenePattern tasks
Interactions with the Scientific Ontology Working Group
Component A
@Publish public DSDataSet publish(. . .) {
DSDataSet dataSet;
// do some work that assigns a value to dataSet.
return dataSet;
}
Component B
@Subscribe public void receive(DSDataSet dataSet, Object source) {
// Consume the argument dataSet, as appropriate
}
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Provide re-usable models of common bioinformatics concepts:
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Data: sequence, expression, genotype, structure, proteomics
Complex data structures: patterns, clusters, HMMs, PSSMs, alignments
Algorithms: Clustering, matching, discovery, normalization, filtering
Provide a foundation for the development of interoperable geWorkbench components
Endorsed by multiple communities (caBIG, AMDeC, NCBCs)
Identifying Specific Tools
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There are tools, databases, and methods that have
universal value across different DBPs.
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What are they?
Which NCBC or external community is producing them
What can we do to standardize their use across the
community.
An Example:
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Molecular Interaction Maps
A Relevant Example That Was Discussed
Molecular Interaction Maps are becoming the
equivalent of an anatomy atlas to map specific
measurements in a functional context; e.g.
QTLs, expression profiles, etc.
Discussion Goal: To determine how relevant these maps are to
the DBPs of the various NCBCs
Limitations: Many Interactomes are limited because they are (1)
too generic (e.g. missing cellular and molecular context), (2) poorly
annotated (e.g. linked only to the specific data used to produce
them), (3) limited to pairwise interactions, (4) lacking quality
control/validation, and (5) not associated to the investigation of
specific biological/biomedical problems.
Example: From Molecular Interaction Maps to
Molecular Interaction Knowledge Bases
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What does it take to turn a ridiculome into a
relevantome?
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Quality control metrics (recall/precision)
Context specificity
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Cellular: Is the interaction specific to a cellular phenotype
Molecular: Is the interaction dependent on the availability of
other molecular species
Links to data (and literature)
Links to analysis of biomedical problems
Focus on specific features (e.g. mechanisms)
A Potential Template for NCBC Knowledge Bases:
MAGNet Human B Lymphocytes Dataset
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Integrative Framework
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Bayesian Evidence integration of pairwise interactions
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Context Specific
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ARACNE, GeneWays, REDUCE
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Protein-Protein, Protein-DNA
Prior Knowledge Incorporation
B-Cell data or B-cell specific criteria
Linked to one of the largest B-Cell expression profiles microarray dataset, ChIPChip assays (MYC/BCL6), miRNA profiles, and Literature
Captures Multi-variate dependencies
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Three-way interactions via MINDY and MATRIXReduce
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Post-translational modulation of transcriptional regulation
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Combinatorial transcriptional regulation
Signal transduction control of Transcriptional Regulation
I.e. the Transferome meets the Transcriptome
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Links to literature (via GeneWays, NCIBI, I2B2, GATE, etc.)
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Other examples? Oncomine (NCIBI), GenePattern ALL/AML, Others?
Some Key Observations from Attendees:
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Systems Biology name is too narrow. Think of Alternatives:
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“Working group to Biomedical Impacts of Computational Biology
at NCBCs” or
NCBC Biomedical Impact Workgroup
Is the intramural program a better place to create atlases and
knowledge bases, since it’s not RO1 funding? They could
implement contract mechanisms with extramural researchers
to leverage outside expertise
Keep in mind that we need to understand what will you deliver
at the end of 4 years, positioning each NCBC for renewal.
Which communities are using the tools? Are they better off?
Individual centers can work to create a specific resourceome
that can be linked and accessible to others
Many working group members had a strong interest in “multiscale” modeling and biological context
Outcomes:
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Create a DBP community within the NCBCs:
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Use this forum to inform target biological communities (not
just NCBCs). E.g. DREAM meeting.
Organize a coordinated effort to evaluate the tools and
technologies and make them interoperable
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ACTION: Coordinate the DBP requirements to drive the
integration of specific tools and data resources
Integrate data and annotation in knowledge bases and
models for related DBPs. Identify other common tools, data,
and methods
Drop the Systems Biology name: Use something like:
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ACTION: Make an interactome map of the existing DBPs with
potential synergies to be published in Symbios magazine
“NCBC Biomedical Impact Workgroup”
Commit to a regular T-con and virtual (Wiki) participation
Consider a yearly retreat of NCBC DBPs possibliy in
collaboration with other NIH roadmap activities (e.g. ICBPs)
NCBC DBP Interactome I: Useful Starting Point
Peter Woolf, NCIBI
Distribution Model: How Can the 7 NCBCs
Effectively Interoperate?
Physics-Based Simulation of
Biological Structures (SIMBIOS)
Russ Altman, PI
National Center for Integrative
Biomedical Informatics (NCIBI)
Brian D. Athey, PI
Informatics for Integrating
Biology and the Bedside (i2b2)
Isaac Kohane, PI
National Alliance for Medical
Imaging Computing (NA-MIC)
Ron Kikinis, PI
The National Center For
Biomedical Ontology (NCBO)
Mark Musen, PI
Multiscale Analysis of Genomic
and Cellular Networks (MAGNet)
Andrea Califano, PI
Center for Computational Biology
(CCB)
Arthur Toga, PI