Sponsored by: Participating Experts: Dr. Uwe Sauer Institute of Molecular Systems Biology Zürich, Switzerland Dr. Albert Fornace Georgetown University Washington, DC Dr. Richard Gross Washington University in St. Louis St. Louis, MO Brought to you by the Science/AAAS Business Office 12 October, 2010 12 October, 2010 Integrated Biology: What is needed to bring Omics together? Integrated Biology: What is needed to bring Omics together? Webinar Series Webinar Series Science Science
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Sponsored by:
Participating Experts:
Dr. Uwe SauerInstitute of Molecular Systems BiologyZürich, Switzerland
Dr. Albert FornaceGeorgetown UniversityWashington, DC
Dr. Richard GrossWashington University in St. LouisSt. Louis, MO
Brought to you by the Science/AAAS Business Office12 October, 201012 October, 2010
Integrated Biology: What isneeded to bring Omics together?Integrated Biology: What isneeded to bring Omics together?
Webinar SeriesWebinar SeriesScienceScience
2
Uwe Sauer, Professor of Systems Biology, ETH Zurich
ETH Zürich | Institute of Process Engineering | Bioprocess Lab | CH-8092 Zürich
Omics Data Integration in Metabolic Research Not only desirable, but necessary for discovery and mechanistic understanding !
• Steady state (baker’s yeast)• Dynamic nutritional adaptations (B. subtilis)
• Although hundreds of transcripts/proteins/ metabolites change, modeling & experimental validation reveals that only very few changes are required for adaptation !
Challenges – Best Practices• Before one can even consider data integration
– Biological variability (in dynamic exps)• all samples from same physical cultures• standardization
– Naming and formatting conventions (one thing - one name)– Combine overlapping dynamic data
• Consensus omics data from different analytical platforms (eg 2D and gel-free proteomics data)
• Replicate time series smoothed/interpolated by Bayesian multicurve regression• Algorithm for metabolomics data smoothing
• Without some type of computational data integration – almost meaningless data piles !
• “Soft” problems– Develop a common language– Leadership at many levels (most effective: small teams with a lead person !)
– Multi-authorship
Sponsored by:
Participating Experts:
Dr. Uwe SauerInstitute of Molecular Systems BiologyZürich, Switzerland
Dr. Albert FornaceGeorgetown UniversityWashington, DC
Dr. Richard GrossWashington University in St. LouisSt. Louis, MO
Brought to you by the Science/AAAS Business Office12 October, 201012 October, 2010
Integrated Biology: What isneeded to bring Omics together?Integrated Biology: What isneeded to bring Omics together?
Webinar SeriesWebinar SeriesScienceScience
Professor of Medicine, Chemistry and Developmental Biology
Richard W. Gross, M.D., Ph.D.
Integration of the “Omics”in Systems Biology
Disclosure:
Dr. Gross has financial interests in:
LipoSpectrumU.S. Patents 7,306,952; and 7,510,880
PlatomicsU.S. Patent 12/174,493
Chemistry Department
Integration of the “Omics”
Genomics
Proteomics
MetabolomicsLipidomics
Traditional Approaches to Systems Biology
Biological Hierarchy of Metabolic Regulation
Bacteria Yeast Mammals
Metabolic Compartmentation
ReceptorsIon Channels and
Transporters
1. Diverse repertoire of discrete chemical species to modulate transmembrane protein activities.
2. Scaffolding for self-organizing chemical assemblies.3. Storage depot for latent 2nd messengers of signal transduction.4. Bilayer medium for membrane trafficking, membrane fusion,
and hormone release.
Functions of Biologic Membranes
Phospholipases
1. The functional sequelae of SNPs and the consequences of alterations in transcript levels can not be routinely predicted in a comprehensive manner.
2. The amount of protein does not necessarily correlate with enzyme activity or protein function due to multiple posttranslational modifications and compartmentation.
3. Examination of whole cell or tissue extracts are not necessarily indicative of the physical interactions between moieties.
Challenges in Integrating the "Omics" to Identify Mechanisms Underlying
Current and Past MembersDivision of Bioorganic Chemistry: Collaborators:
AcknowledgementsAcknowledgements
Sponsored by:
Participating Experts:
Dr. Uwe SauerInstitute of Molecular Systems BiologyZürich, Switzerland
Dr. Albert FornaceGeorgetown UniversityWashington, DC
Dr. Richard GrossWashington University in St. LouisSt. Louis, MO
Brought to you by the Science/AAAS Business Office12 October, 201012 October, 2010
Integrated Biology: What isneeded to bring Omics together?Integrated Biology: What isneeded to bring Omics together?
Webinar SeriesWebinar SeriesScienceScience
Integrated Biology: What is needed to bring the Omics together?
Albert J. Fornace Jr. Professor, Dept. of Biochemistry and Molecular &
Cellular Biology Lombardi Comprehensive Cancer Center
Georgetown University
Gene-Protein-Reactions (GPRs) and Data Integration
Hyduke & Palsson
What is Needed to Bring Omics Together?
• Data management– Clear indication of the source and context of the data– Meaningful identifiers (everybody’s proud of their clever system that nobody else uses)
– Accessible data sources
• Models / Methods to interpret the data– An honest assessment of the benefits and limits of various modeling
approaches– A realistic assessment of the near-term capabilities of current
modeling approaches.
• The ability to understand the limits of the data and models– Complexity of mammalian systems– "As the complexity of the variable increases, it becomes more
important to have a solid model of what you think you can predict and to then test it explicitly, rather than less important as the machine learning enthusiasts would have it." Michael Bittner, TGen
Potential integromics approaches in complex systems
• “Holistic” approach– where a comprehensive list of parameters are assembled from a
sufficiently robust dataset– NCI60 example– application to toxicogenomics and subsequent extension to
additional omics levels
• Genetic approach– p53 signaling at multiple omics levels– Analysis of the role of “ATM” through “omics” analysis