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PLAN LES OUATES, Switzerland

Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.1-1 | Award Amount: 8.71M | Year: 2012

We propose a technology that will sit at the front-end of sequencing pipelines, present and future, and will significantly enhance the quality and throughput of DNA sequencing. Although much attention has been given to throughput/cost of the sequencing process itself, the same cannot be said for the preparation of samples. Identified bottlenecks are (1) sequencing technologies require days of upfront sample preparation which is further increased when sequencing selected parts of the genome; (2) genome assembly relies on computationally intensive comparisons to the reference genome because existing technologies produce short sequence reads; (3) it is difficult to begin with small amounts of sample material comprising micro-biopsies and single cells. The CELL-O-MATIC project will synergize efforts from SMEs, academics and large companies to address these bottlenecks by developing chip-based systems that process DNA from individual cells, ready for next generation high-throughput sequencing. Single cell analysis has numerous applications in systems biology but we will emphasize DNA isolation and sequencing from circulating tumor cells (CTC), which have a strong prognostic value in cancer management. A second innovation will be to develop methods that enable up to whole chromosome lengths of DNA to be contiguously mapped using nanofluidics. The inclusion of nanofluidics makes the project particularly distinctive and introduces European SMEs to an area that so far has been the domain of US companies. A modular prototype comprising, a chip, fluid and thermal control, sonication and optical detection will be developed. Samples prepared using CELL-O-MATIC technology will be benchmarked in a high throughput environment with samples prepared by existing methods. Finally, the information obtained from the CELL-O-MATIC processed sample material will be validated for its utility as an aid to clinical decision making.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 7.62M | Year: 2012

Hematological diseases are highly heterogeneous malignancies in the matter of the molecular mechanisms related to their development and progression. A considerable heterogeneity can be further observed within the same hematological disease at the inter-individual level, being reflected by different clinical outcomes and responses to treatment in different patients. Nowadays, the advent of high-throughput next generation sequencing (NGS) technologies that are revolutionizing genomics and transcriptomics by providing a single base resolution tool for a unified deep analysis of diseases complexity allows a fast and cost-efficient fine-scale assessment of the genetic variability hidden within cohorts of patients affected by the same leukemia. That being so, by potentially highlighting inter-individual differences that may play a role in the differential success of diverse therapeutic interventions, they promise to be crucial for selecting the most appropriate medical treatments. This project aims at developing a European Hematological/NGS platform of scientists for improving outcomes for therapeutic interventions on acute and chronic leukemias and at developing strategies to personalize treatments and tailor therapies to different stratified groups of leukemia patients, with the goal of optimizing their efficacy and safety through a deeper and deeper understanding of the influence of genetic alterations on leukemias pathogenesis and treatment response (i.e. personalized therapy). Moreover, the final aim will be the identification of novel prognostic biomarkers for acute and chronic leukemias, as well as of molecular biomarkers and/or genome-wide profiles for the assessment of minimal residual disease. The originality of this project is to perform systematic deep whole exome/transcriptome studies on well-clinically-characterized leukemia patients, by exploiting NGS technologies able to quickly produce data with a good cost-effectiveness and an unprecedented resolution.

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