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| 2. |
- Auffray, Charles, et al.
(författare)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
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Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 3. |
- Benavides, Raquel, et al.
(författare)
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The GenTree Leaf Collection : Inter- and intraspecific leaf variation in seven forest tree species in Europe
- 2021
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Ingår i: Global Ecology and Biogeography. - : John Wiley & Sons. - 1466-822X .- 1466-8238. ; 30:3, s. 590-597
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Tidskriftsartikel (refereegranskat)abstract
- Motivation Trait variation within species can reveal plastic and/or genetic responses to environmental gradients, and may indicate where local adaptation has occurred. Here, we present a dataset of rangewide variation in leaf traits from seven of the most ecologically and economically important tree species in Europe. Sample collection and trait assessment are embedded in the GenTree project (EU-Horizon 2020), which aims at characterizing the genetic and phenotypic variability of forest tree species to optimize the management and sustainable use of forest genetic resources. Our dataset captures substantial intra- and interspecific leaf phenotypic variability, and provides valuable information for studying the relationship between ecosystem functioning and trait variability of individuals, and the response and resilience of species to environmental changes. Main types of variable contained We chose morphological and chemical characters linked to trade-offs between acquisition and conservation of resources and water use, namely specific leaf area, leaf size, carbon and nitrogen content and their ratio, and the isotopic signature of stable isotope C-13 and N-15 in leaves. Spatial location and grain We surveyed between 18 and 22 populations per species, 141 in total, across Europe. Time period Leaf sampling took place between 2016 and 2017. Major taxa and level of measurement We sampled at least 25 individuals in each population, 3,569 trees in total, and measured traits in 35,755 leaves from seven European tree species, i.e. the conifers Picea abies, Pinus pinaster and Pinus sylvestris, and the broadleaves Betula pendula, Fagus sylvatica, Populus nigra and Quercus petraea. Software format The data files are in ASCII text, tab delimited, not compressed.
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| 4. |
- Chagtai, Tasnim, et al.
(författare)
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Gain of 1q as a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 trial : A SIOP renal tumours biology consortium study
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:26, s. 3195-3203
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods: WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results: One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P < .001; hazard ratio, 2.33) and OS (P = .01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion: Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
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| 5. |
- Friede, Tim, et al.
(författare)
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Recent advances in methodology for clinical trials in small populations : the InSPiRe project
- 2018
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Where there are a limited number of patients, such as in a rare disease, clinical trials in these small populations present several challenges, including statistical issues. This led to an EU FP7 call for proposals in 2013. One of the three projects funded was the Innovative Methodology for Small Populations Research (InSPiRe) project. This paper summarizes the main results of the project, which was completed in 2017. The InSPiRe project has led to development of novel statistical methodology for clinical trials in small populations in four areas. We have explored new decision-making methods for small population clinical trials using a Bayesian decision-theoretic framework to compare costs with potential benefits, developed approaches for targeted treatment trials, enabling simultaneous identification of subgroups and confirmation of treatment effect for these patients, worked on early phase clinical trial design and on extrapolation from adult to pediatric studies, developing methods to enable use of pharmacokinetics and pharmacodynamics data, and also developed improved robust meta-analysis methods for a small number of trials to support the planning, analysis and interpretation of a trial as well as enabling extrapolation between patient groups. In addition to scientific publications, we have contributed to regulatory guidance and produced free software in order to facilitate implementation of the novel methods.
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| 6. |
- Hamperl, Jonas, et al.
(författare)
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High Energy Parametric Laser Source and Frequency-Comb-Based Wavelength Reference for CO2 and Water Vapor DIAL in the 2 mu m Region : Design and Pre-Development Experimentations
- 2021
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Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- We present a differential absorption lidar (DIAL) laser transmitter concept designed around a Nested Cavity Optical Parametric Oscillator (NesCOPO) based Master Oscillator Power Amplifier (MOPA). The spectral bands are located around 2051 nm for CO2 probing and 1982 nm for (H2O)-O-16 and (HDO)-O-16 water vapor isotopes. This laser is aimed at being integrated into an airborne lidar, intended to demonstrate future spaceborne instrument characteristics: high-energy (several tens of mJ nanosecond pulses) and high optical frequency stability (less than a few hundreds of kHz long term drift). For integration and efficiency purposes, the proposed design is oriented toward the use of state-of-the-art high aperture periodically poled nonlinear materials. This approach is supported by numerical calculations and preliminary experimental validations, showing that it is possible to achieve energies in the 40-50 mJ range, reaching the requirement levels for spaceborne Integrated Path Differential Absorption (IPDA) measurements. We also propose a frequency referencing technique based on beat note measurement of the laser signal with a self-stabilized optical frequency comb, which is expected to enable frequency measurement precisions better than a few 100 kHz over tens of seconds integration time, and will then be used to feed the cavity locking of the NesCOPO.
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| 7. |
- Johnson, David, et al.
(författare)
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Dealing with Diversity in Computational Cancer Modeling
- 2013
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Ingår i: Cancer Informatics. - : Libertas Academica Ltd. - 1176-9351. ; 12, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- This paper discusses the need for interconnecting computational cancer models from different sources and scales within clinically relevant scenarios to increase the accuracy of the models and speed up their clinical adaptation, validation, and eventual translation. We briefly review current interoperability efforts drawing upon our experiences with the development of in silico models for predictive oncology within a number of European Commission Virtual Physiological Human initiative projects on cancer. A clinically relevant scenario, addressing brain tumor modeling that illustrates the need for coupling models from different sources and levels of complexity, is described. General approaches to enabling interoperability using XML-based markup languages for biological modeling are reviewed, concluding with a discussion on efforts towards developing cancer-specific XML markup to couple multiple component models for predictive in silico oncology.
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| 8. |
- O'Meara, Elaine, et al.
(författare)
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Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney
- 2012
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 227:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms' Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of similar to 3 kb, incorporating exons 15 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 9. |
- Opgenoorth, Lars, et al.
(författare)
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The GenTree Platform : growth traits and tree-level environmental data in 12 European forest tree species
- 2021
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Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information.Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species' geographic ranges and reflecting local environmental gradients.Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available.
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| 10. |
- Perotti, Daniela, et al.
(författare)
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Hallmark discoveries in the biology of Wilms tumour
- 2023
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Ingår i: Nature Reviews Urology. - 1759-4812.
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Forskningsöversikt (refereegranskat)abstract
- The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the ‘two-hit’ model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics — from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
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