Computational Infrastructures for Large-Scale Data Access and Analysis in Post-Genomic Clinical Trials

Abstract

This Chapter reports on original results of the ACGT integrated project focusing on the design and development of a European Biomedical Grid infrastructure in support of multicentric, post genomic clinical trials on Cancer. ACGT is a FP6-IST research project developing open source middleware services layering to support multicentric, post-genomic Clinical Trials on Cancer. Post Genomic Clinical Trials use multilevel clinical and genomic data and advanced computational analysis and visualization tools to test hypotheses in trying to identify the molecular reasons for a disease and the stratification of patients in terms of treatment. The ultimate goal of the ACGT is to supply a collection of open source services that will be re-used for building complex, discovery driven analytical workflows. This Chapter provides a detailed presentation of the needs of users involved in post-genomic clinical trials, and presents such needs in the form of scenarios which drive the requirements engineering phase of the project. Subsequently, the initial architecture specified by the project is presented and its services are classified and discussed. A key set of such services are those used for wrapping heterogeneous clinical trial management systems and other public biological databases. In addition, the main technological challenge, i.e. the design and development of semantically rich Grid services is discussed. In achieving such an objective, extensive use of ontologies and metadata are required. The Master Ontology on Cancer, developed by the project, is presented and our approach to developing the required metadata registries, which provide semantically rich information about available data and computational services, is also provided. Finally, a discussion of the utilization of the infrastructure for the execution of highly complex computational work, that of modeling and simulation of tumor growth and response to treatment, is presented.