by Jessica Michel Assoumou and Manolis Tsiknakis
During the last four and one-half years, the EU-funded ACGT project (Advancing Clinico-Genomic Trials on cancer: Open Grid Services for improving Medical Knowledge Discovery) managed by ERCIM, has been developing methods and systems for improved medical knowledge discovery and understanding through the integration of biomedical information.
The ACGT project vision has been rooted in the realization that information arising from post-genomics research and genetic and clinical trials is rapidly providing the medical and scientific community with new insights, answers and capabilities when combined with advances in high-performance computing and informatics. The objective of the ACGT project has thus been the provision of a unified technological infrastructure which facilitates the seamless and secure access and analysis of multi-level clinico-genomic data enriched with high-performing knowledge discovery operations and services. Biomedical data and information that have been considered include clinical information relating to tissues, organs or personal health-related information, but also information at the level of molecules and cells, as acquired from genomics and proteomics research.
During the course of its life, the project has defined a detailed architectural blueprint and has developed, tested and validated a range of technologies, such as:
- new, domain-specific ontologies, built on established theoretical foundations and taking into account current initiatives, existing standard data representation models, and reference ontologies
- innovative and powerful data exploitation tools, for example multi-scale modelling and simulation, considering and integrating from the molecular to the systems biology level, and from the organ to the living organism level
- standards for exposing the properties of local sources in a federated environment
- a biomedical grid infrastructure offering seamless mediation services for sharing data and data-processing methods and tools
- advanced security tools including anonymisation and pseudonymisation of personal data according to European legal and ethical regulations
- a ‘Master Ontology on Cancer’ and standard clinical and genomic ontologies and metadata for the semantic integration of heterogeneous databases
- an ontology based ‘Trial Builder’ for helping to easily set up new clinico-genomic trials, to collect clinical, research and administrative data, and to put researchers in the position to perform cross trial analysis
- data and literature mining services in order to support and improve complex knowledge discovery processes.
The technological infrastructure has been validated in a concrete setting of advanced clinical trials on cancer. The project has targeted two major cancer diseases: breast cancer (BRCA) and paediatric nephroblastoma (PN). The Trastuzumab Optimization Trial in Breast Cancer (TOP), a trial which aims at identifying molecular markers that predict response/resistance to one of the most commonly administered chemotherapies in breast cancer, is one of those pilot trials for ACGT. TOP has been selected as demonstration at the final project review to illustrate several procedures and tools set up by ACGT, for example:
- how the trial data is introduced and analyzed in the ACGT infrastructure to identify the targeted biomarkers
- the importance of the ACGT Master Ontology for the semantic integration of heterogeneous data (clinical, imaging, genomic, proteomic, etc).
- how tools developed within ACGT can facilitate the identification of predictive markers of response/resistance for anthracyclines chemotherapy using microarray-based gene expression profiling as well as genotyping technology
- advances made by the in silico oncology working group. This group has evaluatee the reliability of in silico modelling as a tool for assessing alternative cancer treatment strategies; especially in the case of combining and utilizing mixed clinical, imaging and genomic/genetic information and data.
Although the ACGT project is officially ending, the excellent research partnerships developed during the project will continue. The vision of becoming a pan-European voluntary network connecting individuals and institutions while enabling the sharing of data and tools and thus creating a European-wide web of cancer clinical research has been well advanced. The project has developed long lasting partnerships with some of the major stakeholders in the European Cancer Research arena, including ECCO (European Cancer Organisation), BIG (Breast International Group), SIOPE Europe (The European Society for Paediatric Oncology) and the European Clinical Research Infrastructures Network (ECRIN). Building upon the technologies, procedures and knowledge generated by the project, several ACGT partners – jointly with such important end user groups – are about to enter the second phase of implementation. This has been made possible through additional funding form the EU research programmes (both HEALTH and ICT). From legal and ethical aspects to purely ICT solutions, ACGT legacy will be seen under several EU co-financed projects such as the European Network for Cancer Research in Children and Adolescents (ENCCA) and CONTRACT (Consent in a Trial and Care Environment) project that will support the platform created by the ACGT.
In parallel to these developments, the primary instruments for ACGT’s collaborative exploitation are well developed. The Center for Data Protection (CDP) has been established and is already actively engaged in service provision. Also the STaRC Initiative has grown into maturity. STaRC is intended to be a ‘Study, Trial and Research Centre’ that will exploit clinically relevant aspects of ACGT. The concept behind STaRC has received significant recognition and support from patient organisations and patient support groups as well as from some regional governments. The activities for its official initiation are almost complete.
ACGT was an Integrated Project (IP) funded in the 6th Framework Programme of the European Union under the Action Line “Integrated biomedical information for better health”. The project has been carried out by 26 organisations and institutes from academia and industry including the ERCIM members ICS-FORTH (scientific coordinator), INRIA, Computer Architecture Department at the University of Malaga, Technical University of Madrid (both members of SpaRCIM), and Fraunhofer Gesellschaft.
Jessica Michel Assoumou, ERCIM office, France
Manolis Tsiknakis, FORTH-ICS, Greece