| 1. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 6. |
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| 7. |
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| 8. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 9. |
- Aguilar, J. A., et al.
(author)
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Triboelectric backgrounds to radio-based polar ultra-high energy neutrino (UHEN) experiments
- 2023
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 145
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Journal article (peer-reviewed)abstract
- In the hopes of observing the highest-energy neutrinos (E> 1 EeV) populating the Universe, both past (RICE, AURA, ANITA) and current (RNO-G, ARIANNA, ARA and TAROGE-M) polar-sited experiments exploit the impulsive radio emission produced by neutrino interactions. In such experiments, rare single event candidates must be unambiguously identified above backgrounds. Background rejection strategies to date primarily target thermal noise fluctuations and also impulsive radio-frequency signals of anthropogenic origin. In this paper, we consider the possibility that 'fake' neutrino signals may also be generated naturally via the `triboelectric effect' This broadly describes any process in which force applied at a boundary layer results in displacement of surface charge, leading to the production of an electrostatic potential difference AV. Wind blowing over granular surfaces such as snow can induce such a potential difference, with subsequent coronal discharge. Discharges over timescales as short as nanoseconds can then lead to radio-frequency emissions at characteristic MHz-GHz frequencies. Using data from various past (RICE, AURA, SATRA, ANITA) and current (RNO G, ARIANNA and ARA) neutrino experiments, we find evidence for such backgrounds, which are generally characterized by: (a) a threshold wind velocity which likely depends on the experimental trigger criteria and layout; for the experiments considered herein, this value is typically O(10 m/s), (b) frequency spectra generally shifted to the low-end of the frequency regime to which current radio experiments are typically sensitive (100-200 MHz), (c) for the strongest background signals, an apparent preference for discharges from above-surface structures, although the presence of more isotropic, lower amplitude triboelectric discharges cannot be excluded.
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| 10. |
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| 11. |
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| 12. |
- Hirao, Yuki, et al.
(author)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Journal article (peer-reviewed)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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| 13. |
- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 14. |
- Thomas, M, et al.
(author)
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Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity
- 2023
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values<0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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