# Presentation: 867253

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

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

## 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.

## 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.

## BIOlogy

** ****Genomics**

- BIOlogy

- MEDicine

- INFOrmatics

- Organ

** ****Radiology**
** ****- Imaging -**

- System

**     ****Clinic**
-    - Specialty -

**Immunochemistry**
- e-Cell modeling
**Molecular imaging**

- Cell

- Mol. Pathway
- Gene/Protein
- Interactions

**Proteomics**

- Tissue

** ****Histopathology**
**  ****Organ Modeling**
**   **- Simulations -

- Integrated access of Multilevel Biomedical Data

- RNA

**Functional**
**Genomics**

## The ACGT clinical trials

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

## TOP trial

***Neo-adjuvant ***
***Epirubicin x 4/6****** ***

**Can we find ****molecular**** ****signatures related to**
**Anthracycline**** ****response****?**

## TOP trial design

**Neo-adjuvant epirubicin x 4/6**

**SURGERY**

**Adjuvant ****TAXOTERE x 4**

- C1

- C2

- C3

- C4

- C1

- C2

- C3

- C4

- Blood samples (genotyping & proteomic data)
- Biopsies – frozen&fixed (gene-expression profiling, gene copy, molecular markers)

**Tumor sampling**

## 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

## ACGT orientation

- CPU intensive workload Grid as a utility, data Grids, robust infrastructure

- Intra-company, intra community
- e.g. Life Science Grid

- Sharing standard scientific process and data, sharing of common infrastructure

- Between trusted partners

- Sharing of apps and know-how

- With controlled set of unknown clients

- Virtual organisations with dynamic access to unlimited resources

- For all

## Ontologies & Metadata

## Ontology based mediation

## 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

## 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

## B

**I**
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**M**
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**D**
**I**
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**A**
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**N**
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**Y**

## CT end user tools

- Graphical representation of workflows
- Processing modules attached to each other in a workflow

- 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

**An integrated visual environment **

**Notes:**

	How easy is all of this? 

	For the end-users, VL has a friendly user interface, which in theory will allow the end-users to perform all 
 the tasks we  have discussed so far without writing a single program or script. The PFT is completely graphical,  
 present the needed information to the user on demand (usually by a simple click of the mouse button). 
 It communicates with all the other software components of the VL toolkit and convert there output to a human  
 readable form (filling forms, sending queries, composing a data process flow). 

	In Reality the end-user doesn’t use the PFT itself it create an instance and tuned it. As I said one of the
 tasks to be specified is the data flow process: where data is coming from? Which process needs to be applied? 
 On which resource the processes should be executed? And  where the outcome is saved? Mostly this is
 represented in the PFT as simple box by just clicking in the box, the use is provided with another graphical  
interface, which allows him to compose the process flow of the d 

## Workflow for data representation and usege

## Workflows

## CT analysis workflows

**CT analysis workflows**

- Data
- source

- Processing
- engine

- Data
- Mining

- Visualisation

- Resource brokeringand orchestration

## 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

## Scenarios for Clinical Trial Workflows

## Metadata, and workflows in ACGT

**Metadata, and workflows in ACGT**

## Triana used in DataMiningGrid (FhG, FORTH)

- Triana used in DataMiningGrid (FhG, FORTH)

## 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;

## 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.

## The ACGT Organisations

- 1 of 3 integrated projects funded by the IST programme
- Funding: ~18 MEuro, Time plan: 1/2/2006 – 31/1/2010