MAGNet Center: Andrea Califano NCIBI: Brian Athey Simbios: Russ Altman Creating a DBP Community to...
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Transcript of MAGNet Center: Andrea Califano NCIBI: Brian Athey Simbios: Russ Altman Creating a DBP Community to...
MAGNet Center: Andrea Califano
NCIBI: Brian Athey
Simbios: Russ Altman
Creating a DBP Community to Enhance the NCBC Biomedical Impact
NCBC Work Group Report, 18 July 2006
Workgroup Goals Problem: The NCBCs have no workgroup to help build the DBP community
Goal 1: To determine the Mission and Goals for the Applications of Systems Biology, Modeling and Analysis Working Group
Goal 2: To determine how this group would interact with the 2 other NCBC Working Groups to define key sets of: Data Tools Methodologies Ontologies DBPs
Goal 3: Identify NCBC DBPs that are highly motivated to participate in the Working Group
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)
Integrated Computational Biology Platform Support for gene expression data, physics-
based simulations, image analysis, sequences, pathways, structure, etc. (40+ visualization and analysis modules).
Access to local and remote data sources and analytical services.
Support for workflow scripting. Integration with grid infrastructures.
Development framework Open source development. Modular/extensible architecture, supporting
pluggable components with configurable user interface.
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 Many Toolkit and platforms
Internal SimTk Genopia VTK/ITK Brainsuite geWorkbench GenePattern MiMI SAGA miBLAST MarkerInfoFinder
External 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
KNN
WV
SVM
SOM
GSEA
ARACNE
SPLASH
PCA
GenePattern Module Repository
Wrap geWorkbench Wrap geWorkbench modules as modules as GenePattern tasksGenePattern tasks
Execute GenePattern Execute GenePattern modules from within modules from within geWorkbenchgeWorkbench
Interactions with the Scientific Ontology Working Group
@Publish public DSDataSet publish(. . .) { DSDataSet dataSet; // do some work that assigns a value to dataSet. return dataSet;}
@Subscribe public void receive(DSDataSet dataSet, Object source) { // Consume the argument dataSet, as appropriate}
Provide re-usable models of common bioinformatics concepts: 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)
Component A
Component B
Identifying Specific Tools
There are tools, databases, and methods that have universal value across different DBPs. What are they? Which NCBC or external community is producing them What can we do to standardize their use across the
community.
An Example: 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
What does it take to turn a ridiculome into a relevantome? Quality control metrics (recall/precision) Context specificity
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 Integrative Framework
Bayesian Evidence integration of pairwise interactions Protein-Protein, Protein-DNA Prior Knowledge Incorporation
Context Specific ARACNE, GeneWays, REDUCE
B-Cell data or B-cell specific criteria Linked to one of the largest B-Cell expression profiles microarray dataset, ChIP-
Chip assays (MYC/BCL6), miRNA profiles, and Literature
Captures Multi-variate dependencies Three-way interactions via MINDY and MATRIXReduce
Post-translational modulation of transcriptional regulation Combinatorial transcriptional regulation Signal transduction control of Transcriptional Regulation
I.e. the Transferome meets the Transcriptome
Links to literature (via GeneWays, NCIBI, I2B2, GATE, etc.)
Other examples? Oncomine (NCIBI), GenePattern ALL/AML, Others?
Example
Some Key Observations from Attendees:
Systems Biology name is too narrow. Think of Alternatives: “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 “multi-scale” modeling and biological context
Outcomes:
Create a DBP community within the NCBCs: ACTION: Make an interactome map of the existing DBPs with
potential synergies to be published in Symbios magazine 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 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: “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)
Distribution Model: How Can the 7 NCBCs Effectively Interoperate?
Informatics for IntegratingBiology and the Bedside (i2b2)Isaac Kohane, PI
Center for Computational Biology(CCB)Arthur Toga, PI
Multiscale Analysis of Genomicand Cellular Networks (MAGNet)Andrea Califano, PI
National Alliance for MedicalImaging Computing (NA-MIC)Ron Kikinis, PI
The National Center ForBiomedical Ontology (NCBO)Mark Musen, PI
Physics-Based Simulation ofBiological Structures (SIMBIOS)Russ Altman, PI
National Center for Integrative Biomedical Informatics (NCIBI) Brian D. Athey, PI