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HIGH PERFORMANCE COMPUTING
FOR INTEGRATIVE
CARDIOVASCULAR DRUG DESIGN
1Patrizio
Arrigo, 2Carmelina Ruggiero
1CNR
2DIST
ISMAC, Genoa, Italy
- University of Genoa, Italy
Changes in Life Science Research in
Pre-genomics and Post-genomic era
Pre-genomics
Small dataset
Limited data reuse
Limited data sharing
Post-genomics
Massive dataset
Extensive data reuse
Extensive data
Data production
sharing
and analysis
Straight-forward
Complex data
analysis
Manual analysis
Computer based
analysis
Relative low costs
Very high costs
Hypothesis-driven
Data-driven
Experimentation
Easy design of
Complex experiment
experiments
design
Reductionist
holistic
Mono-disciplinary
Multi-disciplinary
Research approach experimental
Conceptual
Limited collaboration Extensive
collaborations
Long-standing
Flexible virtual
collaboration
organization
Conventional science E-science
Molecular medicine approach in the
post-genomics era
Diagnostics
screening
Determination
Of the genetic
Component of the
Disease
Investigation of
Molecular mechanism of
the diseases
Pharmacogenomics
Gene
screening
Gene Therapy
Therapeutic
Target identification
And validation
An Integrative Virtual Drug Design Laboratory
(IVDDL)
Requirements:
•Database federation and heterogeneous data sources
integration
•Development of high performance information and
communication technology drivers that allow to
synchronize and optimize the integrative Knowledge
discovery process
•Optimization of the data mining process: computer
intensive tools for specific processes can reduce
computation time
•Integration with Virtual Screening systems
Basic Architecture for a Virtual Laboratory
(VL)
3
1
level
2
Hypothesis
generation
Knowledge
Discovery
Infrastructure
Experiment
design
Wet and
In silico
experiments
Experimental
Infrastructure
(Wet-Laboratory)
Enhancement
Of Knowledge
Decision Support
System Infrastructure
Communication Infrastructure
CARDIOWORKBENCH Partners
•University of Genoa (DIST-Unige), Italy
•University of Ulster, United Kingdom
•University of Tartu, Estonia
•National Research Council (CNR ISMAC), Italy
•Bielefeld University (UNIBI), Germany
•University of Leipzig, Germany
•University of Milan (UMIL), Italy
•Vienna Medical University (VMU), Austria
•Fraunhofer Institute for Biomedical Engineering (Fraunhofer), Germany
•Pharmacelsus (PHARMACEL), Germany
•Chemilia AB, Sweden
•Novamass Analytical Ltd (NOVAMASS), Finland
THE CARDIOWORKBENCH PROJECT
CARDIOWORKBENCH addresses bottlenecks in the drug design and the optimization
of knowledge transfer in join research activities that involve industrial and academicals
entities. The main activities of the project are the following:
•DNA Array technology
•High throughput proteomic analysis
•Integration of functional genomics and proteomics data mining
•Experimental dissection of metabolic pathways
•Determination of structural characteristics of the screened targets
•Quantitative activity and structural relationship (QSAR) and protein-ligand interaction
analysis
•Development of ADME and pharmacokinetic analysis system based on “in silico”
tissue computational models
•Evaluation of the interaction among metabolic pathways
•Modelling cellular behaviour on the basis of metabolic data
•Optimization of cell culture parameters
CARDIOWORKBENCH Architecture and
workflow
Mathematical modeling
Of metabolic pathway
Data Sources used in CARDIOWORKBENCH
DNA microarray
Existing Drug
Database
Phenotype
Genetic varabiality Database
Gene
Cardiovascular
Disease
Cellular Data
Proteomic analysis
Metabolic Pathways
Existing Ligand
Database
3D Structure
Interacting proteins
Relevant components of proposed GRID
infrastructure in CARDIOWORKBENCH
Data Warehouse
-Public data (molecular biology and
chemical data)
-Project data (clinical and experimental
data)
Data Mining
Bioinformatic and chemoinformatic
Virtual screening
-Fragment library generation (preliminary to
Docking)
-Optimization of structure generation
-QSPR/QSAR models development
CARDIOWORKBENCH functional
Bioinformatics resources
CARDIOWORKBENCH
data base
FUNCTIONAL
GENOMICS:
Integrative knowledge
discovery
-Microarray
-RNA Interference
PROTEOMICS:
-Antibody array
-Protein chip
Chemoinformatics
Knowledge discovery
System biology
modelling
Chemoinformatic Knowledge discovery
CARDIOWORKBENCH
data base
Structural property
analysis
Chemical data base
screening
QSAR analysis
Chemical
synthesis
System modeling module
Metabolic compartment modelling
Compartment model integrator
Metabolic compartment modelling
CARDIOWORKBENCH integrated high
performance resources
BIELEFELD Integrative
Bioinformatic Server
DIST Project Server
TARTU Computational
Chemistry Server
University of Vienna
ISMAC system biology
modelling Server
Data Mining Server
University of Ulster
Advantages of GRID
for CARDIOWORKBENCH
•Avalability of the computational tools of
for data communication and exchange
•Distribution of heavy computational tasks
(computational chemistry etc)
• Agent based technology for information
filtering
• Flexyble workflow design for integrative
data mining