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- Brownstein, Catherine A., et al.
(author)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Journal article (peer-reviewed)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Soler, J. M., et al.
(author)
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Predictive Modeling of a Simple Field Matrix Diffusion Experiment Addressing Radionuclide Transport in Fractured Rock. Is It So Straightforward?
- 2022
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In: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 208:6, s. 1059-1073
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Journal article (peer-reviewed)abstract
- The SKB GroundWater Flow and Transport of Solutes Task Force is an international forum in the area of conceptual and numerical modeling of groundwater flow and solute transport in fractured rocks relevant for the deep geological disposal of radioactive waste. Two in situ matrix diffusion experiments in crystalline rock (gneiss) were performed at POSIVA’s ONKALO underground facility in Finland. Synthetic groundwater containing several conservative and sorbing radiotracers was injected at one end of a borehole interval and flowed along a thin annulus toward the opposite end. Several teams performed predictive modeling of the tracer breakthrough curves using “conventional” modeling approaches (constant diffusion and sorption in the rock, no or minimum rock heterogeneity). Supporting information, derived from small-scale laboratory experiments, was provided. The teams were free to implement different concepts, use different codes, and apply the transport and retention parameters that they considered to be most suited (i.e., not a benchmark exercise). The main goal was the comparison of the different sets of results and the analysis of the possible differences for this relatively simple experimental setup with a well-defined geometry. Even though the experiment was designed to study matrix diffusion, the calculated peaks of the breakthrough curves were very sensitive to the assumed magnitude of dispersion in the borehole annulus. However, given the very different timescales for advection and matrix diffusion, the tails of the curves provided information concerning diffusion and retention in the rock matrix regardless of the magnitude of dispersion. In addition, although the task was designed to be a blind modeling exercise, the model results have also been compared to the measured experimental breakthroughs. Experimental results tend to show relatively small activities, wide breakthroughs, and early first arrivals, which are somewhat similar to model results using large dispersivity values.
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