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- Wang, Anqi, et al.
(author)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Aleksich, Mariya, et al.
(author)
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XFEL Microcrystallography of Self-Assembling Silver n-Alkanethiolates
- 2023
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In: Journal of the American Chemical Society. - 0002-7863. ; 145:31, s. 17042-17055
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Journal article (peer-reviewed)abstract
- New synthetic hybrid materials and their increasing complexity have placed growing demands on crystal growth for single-crystal X-ray diffraction analysis. Unfortunately, not all chemical systems are conducive to the isolation of single crystals for traditional characterization. Here, small-molecule serial femtosecond crystallography (smSFX) at atomic resolution (0.833 Å) is employed to characterize microcrystalline silver n-alkanethiolates with various alkyl chain lengths at X-ray free electron laser facilities, resolving long-standing controversies regarding the atomic connectivity and odd-even effects of layer stacking. smSFX provides high-quality crystal structures directly from the powder of the true unknowns, a capability that is particularly useful for systems having notoriously small or defective crystals. We present crystal structures of silver n-butanethiolate (C4), silver n-hexanethiolate (C6), and silver n-nonanethiolate (C9). We show that an odd-even effect originates from the orientation of the terminal methyl group and its role in packing efficiency. We also propose a secondary odd-even effect involving multiple mosaic blocks in the crystals containing even-numbered chains, identified by selected-area electron diffraction measurements. We conclude with a discussion of the merits of the synthetic preparation for the preparation of microdiffraction specimens and compare the long-range order in these crystals to that of self-assembled monolayers.
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- Feng, Shaohong, et al.
(author)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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- Ibrahim, A. Y., et al.
(author)
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An X-Ray and Radio View of the 2022 Reactivation of the Magnetar SGR J1935+2154
- 2024
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In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 965:1
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Journal article (peer-reviewed)abstract
- Recently, the Galactic magnetar SGR J1935+2154 has garnered attention due to its emission of an extremely luminous radio burst, reminiscent of fast radio bursts (FRBs). SGR J1935+2154 is one of the most active magnetars, displaying flaring events nearly every year, including outbursts as well as short and intermediate bursts. Here, we present our results on the properties of the persistent and bursting X-ray emission from SGR J1935+2154 during the initial weeks following its outburst on 2022 October 10. The source was observed with XMM-Newton and NuSTAR (quasi-)simultaneously during two epochs, separated by ∼5 days. The persistent emission spectrum is well described by an absorbed blackbody plus power-law model up to an energy of ∼25 keV. No significant changes were observed in the blackbody temperature (kT BB ∼ 0.4 keV) and emitting radius (R BB ∼ 1.9 km) between the two epochs. However, we observed a slight variation in the power-law parameters. Moreover, we detected X-ray pulsations in all the data sets and derived a spin-period derivative of P ̇ = 5.52 ( 5 ) × 10 − 11 s s−1. This is 3.8 times larger than the value measured after the first recorded outburst in 2014. Additionally, we performed quasi-simultaneous radio observations using three 25-32 m class radio telescopes for a total of 92.5 hr to search for FRB-like radio bursts and pulsed emission. However, our analysis did not reveal any radio bursts or periodic emission.
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