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- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 2. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 3. |
- Alef, S., et al.
(författare)
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The BGOOD experimental setup at ELSA
- 2020
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:4
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Tidskriftsartikel (refereegranskat)abstract
- The BGOOD experiment at the ELSA facility in Bonn has been commissioned within the framework of an international collaboration. The experiment pursues a systematic investigation of non-strange and strange meson photoproduction, in particular t-channel processes at low momentum transfer. The setup uniquely combines a central almost 4 π acceptance BGO crystal calorimeter with a large aperture forward magnetic spectrometer providing excellent detection of both neutral and charged particles, complementary to other setups such as Crystal Barrel, Crystal Ball, LEPS and CLAS.
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| 8. |
- Dutkiewicz, Stephanie, et al.
(författare)
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Multiple biotic interactions establish phytoplankton community structure across environmental gradients
- 2024
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590.
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Tidskriftsartikel (refereegranskat)abstract
- The combination of taxa and size classes of phytoplankton that coexist at any location affects the structure of the marine food web and the magnitude of carbon fluxes to the deep ocean. But what controls the patterns of this community structure across environmental gradients remains unclear. Here, we focus on the North East Pacific Transition Zone, a similar to 10 degrees region of latitude straddling warm, nutrient-poor subtropical and cold, nutrient-rich subpolar gyres. Data from three cruises to the region revealed intricate patterns of phytoplankton community structure: poleward increases in the number of cell size classes; increasing biomass of picoeukaryotes and diatoms; decreases in diazotrophs and Prochlorococcus; and both increases and decreases in Synechococcus. These patterns can only be partially explained by existing theories. Using data, theory, and numerical simulations, we show that the patterns of plankton distributions across the transition zone are the result of gradients in nutrient supply rates, which control a range of complex biotic interactions. We examine how interactions such as size-specific grazing, multiple trophic strategies, shared grazing between several phytoplankton size classes and heterotrophic bacteria, and competition for multiple resources can individually explain aspects of the observed community structure. However, it is the combination of all these interactions together that is needed to explain the bulk compositional patterns in phytoplankton across the North East Pacific Transition Zone. The synthesis of multiple mechanisms is essential for us to begin to understand the shaping of community structure over large environmental gradients.
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