The identification of novel biological factors associated with thrombin generation, a key biomarker of the coagulation process, remains a relevant strategy to disentangle pathophysiological mechanisms underlying the risk of venous thrombosis (VT). As part of the MARseille THrombosis Association Study (MARTHA), we measured whole blood DNA methylation levels, plasma levels of 300 proteins, 3 thrombin generation biomarkers (endogeneous thrombin potential, peak and lagtime), clinical and genetic data in 700 patients with VT. The application of a novel high-dimensional multi-levels statistical methodology we recently developed, the data driven sparse Partial Least Square method (ddsPLS), on the MARTHA datasets enabled us 1/ to confirm the role of a known mutation of the variability of endogenous thrombin potential and peak, 2/ to identify a new signature of 7 proteins strongly associated with lagtime.

Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

We present the implementation and analysis of a market-based resource allocation system for computational grids. Although grids provide a way to share resources and take advantage of statistical multiplexing, a variety of challenges remain. One is the economically efficient allocation of resources to users from disparate organizations who have their own and sometimes conflicting requirements for both the quantity and quality of services. Another is secure and scalable authorization despite rapidly changing allocations. Our solution to both of these challenges is to use a market-based resource allocation system. This system allows users to express diverse quantity- and quality-of-service requirements, yet prevents them from denying service to other users. It does this by providing tools to the user to predict and tradeoff risk and expected return in the computational market. In addition, the system enables secure and scalable authorization by using signed money-transfer tokens instead of identity-based authorization. This removes the overhead of maintaining and updating access control lists, while restricting usage based on the amount of money transferred. We examine the performance of the system by running a bioinformatics application on a fully operational implementation of an integrated grid market