| 1. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 2. |
- Wang, Y., et al.
(författare)
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Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers
- 2018
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 10:433, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease. In contrast, only 1.4% of 714 women without cancer had positive Pap brush samples (specificity, ~99%). Next, we showed that intrauterine sampling with a Tao brush increased the detection of malignancy over endocervical sampling with a Pap brush: 93% of 123 (95% CI, 87 to 97%) patients with endometrial cancer and 45% of 51 (95% CI, 31 to 60%) patients with ovarian cancer were positive, whereas none of the samples from 125 women without cancer were positive (specificity, 100%). Finally, in 83 ovarian cancer patients in whom plasma was available, circulating tumor DNA was found in 43% of patients (95% CI, 33 to 55%). When plasma and Pap brush samples were both tested, the sensitivity for ovarian cancer increased to 63% (95% CI, 51 to 73%). These results demonstrate the potential of mutation-based diagnostics to detect gynecologic cancers at a stage when they are more likely to be curable.
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| 3. |
- Andrews, Timothy, et al.
(författare)
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On the Effect of Historical SST Patterns on Radiative Feedback
- 2022
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:18
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the dependence of radiative feedback on the pattern of sea-surface temperature (SST) change in 14 Atmospheric General Circulation Models (AGCMs) forced with observed variations in SST and sea-ice over the historical record from 1871 to near-present. We find that over 1871–1980, the Earth warmed with feedbacks largely consistent and strongly correlated with long-term climate sensitivity feedbacks (diagnosed from corresponding atmosphere-ocean GCM abrupt-4xCO2 simulations). Post 1980, however, the Earth warmed with unusual trends in tropical Pacific SSTs (enhanced warming in the west, cooling in the east) and cooling in the Southern Ocean that drove climate feedback to be uncorrelated with—and indicating much lower climate sensitivity than—that expected for long-term CO2 increase. We show that these conclusions are not strongly dependent on the Atmospheric Model Intercomparison Project (AMIP) II SST data set used to force the AGCMs, though the magnitude of feedback post 1980 is generally smaller in nine AGCMs forced with alternative HadISST1 SST boundary conditions. We quantify a “pattern effect” (defined as the difference between historical and long-term CO2 feedback) equal to 0.48 ± 0.47 [5%–95%] W m−2 K−1 for the time-period 1871–2010 when the AGCMs are forced with HadISST1 SSTs, or 0.70 ± 0.47 [5%–95%] W m−2 K−1 when forced with AMIP II SSTs. Assessed changes in the Earth's historical energy budget agree with the AGCM feedback estimates. Furthermore satellite observations of changes in top-of-atmosphere radiative fluxes since 1985 suggest that the pattern effect was particularly strong over recent decades but may be waning post 2014.
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| 4. |
- Gutjahr, Marcus, et al.
(författare)
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Sub‐Permil Interlaboratory Consistency for Solution‐Based Boron Isotope Analyses on Marine Carbonates
- 2021
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Ingår i: Geostandards and Geoanalytical Research. - : John Wiley & Sons. - 1639-4488 .- 1751-908X. ; 45:1, s. 59-75
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Tidskriftsartikel (refereegranskat)abstract
- Boron isotopes in marine carbonates are increasingly used to reconstruct seawater pH and atmospheric pCO2 through Earth’s history. While isotope ratio measurements from individual laboratories are often of high quality, it is important that records generated in different laboratories can equally be compared. Within this Boron Isotope Intercomparison Project (BIIP), we characterised the boron isotopic composition (commonly expressed in δ11B) of two marine carbonates: Geological Survey of Japan carbonate reference materials JCp‐1 (coral Porites) and JCt‐1 (giant clam Tridacna gigas). Our study has three foci: (i) to assess the extent to which oxidative pre‐treatment, aimed at removing organic material from carbonate, can influence the resulting δ11B; (ii) to determine to what degree the chosen analytical approach may affect the resultant δ11B, and (iii) to provide well‐constrained consensus δ11B values for JCp‐1 and JCt‐1. The resultant robust mean and associated robust standard deviation (s*) for un‐oxidised JCp‐1 is 24.36 ± 0.45‰ (2s*), compared with 24.25 ± 0.22‰ (2s*) for the same oxidised material. For un‐oxidised JCt‐1, respective compositions are 16.39 ± 0.60‰ (2s*; un‐oxidised) and 16.24 ± 0.38‰ (2s*; oxidised). The consistency between laboratories is generally better if carbonate powders were oxidatively cleaned prior to purification and measurement.
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