| 1. |
- Calabrese, Claudia, et al.
(author)
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Genomic basis for RNA alterations in cancer
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
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Journal article (peer-reviewed)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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| 2. |
- Chrysafi, Anna, et al.
(author)
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Quantifying Earth system interactions for sustainable food production via expert elicitation
- 2022
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In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 5:10, s. 830-842
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Journal article (peer-reviewed)abstract
- Several safe boundaries of critical Earth system processes have already been crossed due to human perturbations; not accounting for their interactions may further narrow the safe operating space for humanity. Using expert knowledge elicitation, we explored interactions among seven variables representing Earth system processes relevant to food production, identifying many interactions little explored in Earth system literature. We found that green water and land system change affect other Earth system processes strongly, while land, freshwater and ocean components of biosphere integrity are the most impacted by other Earth system processes, most notably blue water and biogeochemical flows. We also mapped a complex network of mechanisms mediating these interactions and created a future research prioritization scheme based on interaction strengths and existing knowledge gaps. Our study improves the understanding of Earth system interactions, with sustainability implications including improved Earth system modelling and more explicit biophysical limits for future food production.
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| 3. |
- Ferguson, Lyn D, et al.
(author)
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Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity : a cross-sectional study
- 2021
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:4, s. 1858-1862
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease.METHODS: Detailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls.RESULTS: PsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (s.d. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (s.d. 1.83 l)] (P <0.001) and liver fat percentage [median 8.88% (interquartile range 4.42-13.18%)] compared with MDF controls [3.29% (1.98-7.25%)] (P <0.001). These differences remained significant after adjustment for age, sex and BMI. There were no statistically significant differences in VAT, liver fat or muscle fat infiltration (MFI) between PsA and type 2 diabetes. PsA participants had a lower thigh muscle volume than MDF controls and those with type 2 diabetes. Body composition-predicted propensity for CHD and type 2 diabetes was 1.27 and 1.83 times higher, respectively, for PsA compared with matched-MDF controls.CONCLUSION: Individuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk.
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| 4. |
- Fluet-Chouinard, Etienne, et al.
(author)
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Extensive global wetland loss over the past three centuries
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 614:7947, s. 281-286
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Journal article (peer-reviewed)abstract
- Wetlands have long been drained for human use, thereby strongly affecting greenhouse gas fluxes, flood control, nutrient cycling and biodiversity1,2. Nevertheless, the global extent of natural wetland loss remains remarkably uncertain3. Here, we reconstruct the spatial distribution and timing of wetland loss through conversion to seven human land uses between 1700 and 2020, by combining national and subnational records of drainage and conversion with land-use maps and simulated wetland extents. We estimate that 3.4 million km2 (confidence interval 2.9–3.8) of inland wetlands have been lost since 1700, primarily for conversion to croplands. This net loss of 21% (confidence interval 16–23%) of global wetland area is lower than that suggested previously by extrapolations of data disproportionately from high-loss regions. Wetland loss has been concentrated in Europe, the United States and China, and rapidly expanded during the mid-twentieth century. Our reconstruction elucidates the timing and land-use drivers of global wetland losses, providing an improved historical baseline to guide assessment of wetland loss impact on Earth system processes, conservation planning to protect remaining wetlands and prioritization of sites for wetland restoration4.
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| 5. |
- Hering, Alessa, et al.
(author)
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Learn2Reg: comprehensive multi-task medical image registration challenge, dataset and evaluation in the era of deep learning
- 2023
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In: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 42:3, s. 697-712
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Journal article (peer-reviewed)abstract
- Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https:// learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.
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| 6. |
- Räsänen, Matti, et al.
(author)
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The effect of rainfall amount and timing on annual transpiration in a grazed savanna grassland
- 2022
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In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 26:22, s. 5773-5791
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Journal article (peer-reviewed)abstract
- The role of precipitation (P) variability with respect to evapotranspiration (ET) and its two components, transpiration (T) and evaporation (E), from savannas continues to draw significant research interest given its relevance to a number of ecohydrological applications. Our study reports on 6 years of measured ET and estimated T and E from a grazed savanna grassland at Welgegund, South Africa. Annual P varied significantly with respect to amount (508 to 672 mm yr-1), with dry years characterized by infrequent early-season rainfall. T was determined using annual water-use efficiency and gross primary production estimates derived from eddy-covariance measurements of latent heat flux and net ecosystem CO2 exchange rates. The computed annual T for the 4 wet years with frequent early wet-season rainfall was nearly constant, 326±19 mm yr-1 (T/ET=0.51), but was lower and more variable between the 2 dry years (255 and 154 mm yr-1, respectively). Annual T and T/ET were linearly related to the early wet-season storm frequency. The constancy of annual T during wet years is explained by the moderate water stress of C4 grasses as well as trees' ability to use water from deeper layers. During extreme drought, grasses respond to water availability with a dieback-regrowth pattern, reducing leaf area and transpiration and, thus, increasing the proportion of transpiration contributed by trees. The works suggest that the early-season P distribution explains the interannual variability in T, which should be considered when managing grazing and fodder production in these grasslands.
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| 7. |
- Sandström, Vilma, et al.
(author)
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Food system by-products upcycled in livestock and aquaculture feeds can increase global food supply
- 2022
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In: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 3:9, s. 729-740
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Journal article (peer-reviewed)abstract
- Many livestock and aquaculture feeds compete for resources with food production. Increasing the use of food system by-products and residues as feed could reduce this competition. We gathered data on global food system material flows for crop, livestock and aquaculture production, focusing on feed use and the availability of by-products and residues. We then analysed the potential of replacing food-competing feedstuff—here cereals, whole fish, vegetable oils and pulses that account for 15% of total feed use—with food system by-products and residues. Considering the nutritional requirements of food-producing animals, including farmed aquatic species, this replacement could increase the current global food supply by up to 13% (10–16%) in terms of kcal and 15% (12–19%) in terms of protein content. Increasing the use of food system by-products as feed has considerable potential, particularly when combined with other measures, in the much-needed transition towards circular food systems.
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