ACGT: Open Grid Services for Improving Medical Knowledge Discovery A European Biomedical Informatics

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ACGTOpen Grid Services for Improving Medical
Knowledge Discovery A European Biomedical
Informatics Grid initiative

• M. Tsiknakis, D. Kafetzopoulos, A. Kumar

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ACGT details

• The ACGT concept resulted from experiences in
  running large, multi-site, post-genomic,
  translational clinical trials
• International Society of Paediatric Oncology
  (SIOP) - SIOP 2001/GPOH concerned with Wilms
  tumour (nephroblastoma).
• TransBIG - Translating molecular knowledge into
  early breast cancer management. European
  Commission under its FP6 programme. 45 sites in
  25 countries.
• PrognoChip, a multi-site national study aiming
  at the identification and validation of
  signature gene expression profiles of breast
  tumours.

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The ACGT vision principles

• The ultimate objective of the ACGT project is the
  provision of a unified technological
  infrastructure which will facilitate
• integrated access to multi-level biomedical data
• development or re-use of open source analytical
  tools, accompanied with the appropriate meta-data
  allowing their discovery and orchestration into
  complex workflows.
• ACGT
• focuses on clinical trials on Cancer (Wilms
  tumor, Breast) and
• is based on the principles of
• Open access (among trusted partners)
• Open source
• is not a standards generating exercise but a
  standards adopting one.

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Integrated access of Multilevel Biomedical Data
System
Clinic - Specialty -
Organ
Radiology - Imaging -
MEDicine
Tissue
Histopathology Organ Modeling - Simulations
-
INFOrmatics
Cell
Immunochemistry e-Cell modeling Molecular imaging
Mol. Pathway Gene/Protein Interactions
Proteomics
BIOlogy
RNA
Functional Genomics
DNA ACGTTCGCT
Genomics
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The ACGT clinical trials

• Multicentric TOP trial Breast Cancer
• SIOP 2002 paediatric nephroblastoma
• In Silico modeling and simulation of tumor growth
  response to treatment

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TOP trial
Neo-adjuvant Epirubicin x 4/6
Can we find molecular signatures related
to Anthracycline response?
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TOP trial design
Tumor sampling
SURGERY
Neo-adjuvant epirubicin x 4/6
Adjuvant TAXOTERE x 4
Diagnosis
C1
C2
C3
C4
C1
C3
C4
C2
Blood samples (genotyping proteomic
data) Biopsies frozenfixed (gene-expression
profiling, gene copy, molecular markers)
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In silico modeling and simulation

• Seeks to extract information related to tumor
  growth response to treatment
• Requires
• access to multi-level clinico-genomic data.
• implementation of a variety of processing tools
  and
• specification of complex analytical workflows

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ACGT orientation
Virtual organisations with dynamic access to
unlimited resources
For all
Sharing of apps and know-how
With controlled set of unknown clients
Sharing standard scientific process and data,
sharing of common infrastructure
Between trusted partners
CPU intensive workload Grid as a utility, data
Grids, robust infrastructure
Intra-company, intra community e.g. Life Science
Grid
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• Ontologies Metadata

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Ontology based mediation
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Goal of the ACGT ontology

• Priority Ontology of entities involved in two
  carcinomas
• Nephroblastoma and Breast Carcinoma
• Basis for creation of databases and CRFs
• Constant extensibility ability to draw
  inferences computationally
• Use anatomy axis as basis of manual entry into
  ontology and provide another partition once
  anatomy axis is exhausted
• Urinary system Urinary Tract Upper Urinary
  Tract Kidney
• Disease of Urinary System - Disease of Kidney
  Renal Neoplasm

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Sources of terms

• Terms from different terminologies ontologies
  are integrated together
• Hierarchy and Relations of terminologies
  ontologies NOT incorporated (except FMA)
• Sources used as a dictionary
• Deficiencies present in each source in
  classificationand relations improved
• Possible collaboration with GRID services to
  access the Source foreseen

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B I O M E D I C A L O N T O L O G Y
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CT end user tools
An integrated visual environment

• Clinical Trial Templates
• Augmented by the ACGT Master Ontology
• Graphical representation of data elements and
  processing steps in a clinical trial
• Context-sensitive assistance

• Data mining and analytical tools
• A variety of tools and applications

• Clinical trial workflows
• Graphical representation of workflows
• Processing modules attached to each other in a
  workflow

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Workflow for data representation and usege
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• Workflows

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CT analysis workflows
Resource brokeringand orchestration
Data source
Processing engine
Data Mining
Visualisation
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Overview of requirements

• We do NOT yet know all analytical services which
  will be required, but
• Accessing multilevel data will not be enough.
  The data will need to be integrated, processed,
  transformed, analyzed, etc
• Analytical services must be presented as Grid
  Services and provide APIs for discovering and
  invoking the service
• The analytical services, just as the data access
  services, will take in and return semantically
  harmonized data types
• Must provide AnalyticalServiceMetadata describing
  the service

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Scenarios for Clinical Trial Workflows
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Metadata, and workflows in ACGT
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Triana used in DataMiningGrid (FhG, FORTH)
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Main challenges Semantic Integration

• Middleware technology, enabling large-scale
  (semantic, structural, and syntactic)
  interoperation among biomedical resources and
  services on an as-needed basis
• Shared mediator ontology through semantic
  modelling of biomedical concepts using existing
  ontologies and ontologies developed for the needs
  of the project
• Mapping of local conceptual models (clinical,
  genomic) to the shared ontology while checking
  consistency and integrity of the mapped
  information
• Semantic annotation and advertisement of
  biomedical resources, to allow metadata-based
  discovery and query of tools, and services
• Mata-data descriptions of clinical trials to
  provide adequate provenance information for
  future re-use, comparison, and integration of
  results

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Concluding remarks

• ACGT is promoting
• the adoption of standards and
• the re-use results of others.
• As a result we are here
• to learn and talk to people,
• to exchange experiences and
• to explore possibilities for common actions.
• Areas of possible collaboration harmonization
• Harmonization initiatives
• Meta-data description of analytical tools so
  that they can be discovered, invoked and
  integrated into our CT workflows
• Joined study of legal, security issues related to
  the intenationalisation of CTs.
• Promotion of the common basic principles.

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The ACGT Organisations
1 of 3 integrated projects funded by the IST
programme Funding 18 MEuro, Time plan 1/2/2006
31/1/2010