ACGT: advancing clinico-genomic trials on cancer - four years of experience.

The challenges regarding seamless integration of distributed, heterogeneous and multilevel data arising in the context of contemporary, post-genomic clinical trials cannot be effectively addressed with current methodologies. An urgent need exists to access data in a uniform manner, to share information among different clinical and research centers, and to store data in secure repositories assuring the privacy of patients. Advancing Clinico-Genomic Trials (ACGT) was a European Commission funded Integrated Project that aimed at providing tools and methods to enhance the efficiency of clinical trials in the -omics era. The project, now completed after four years of work, involved the development of both a set of methodological approaches as well as tools and services and its testing in the context of real-world clinico-genomic scenarios. This paper describes the main experiences using the ACGT platform and its tools within one such scenario and highlights the very promising results obtained.

Variance and covariance of actual relationship between relatives at one locus.

The relationship between pairs of individuals is an important topic in many areas of population and quantitative genetics. It is usually measured as the proportion of thegenome identical by descent shared by the pair and it can be inferred from pedigree information. But there is a variance in actual relationships as a consequence of Mendelian sampling, whose general formula has not been developed. The goal of this work is to develop this general formula for the one-locus situation,. We provide simple expressions for the variances and covariances of all actual relationships in an arbitrary complex pedigree. The proposed method relies on the use of the nine identity coefficients and the generalized relationship coefficients; formulas have been checked by computer simulation. Finally two examples for a short pedigree of dogs and a long pedigree of sheep are given.