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- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 4. |
- Pustovalova, Y., et al.
(författare)
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NUScon: a community-driven platform for quantitative evaluation of nonuniform sampling in NMR
- 2021
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Ingår i: Magnetic Resonance. - : Copernicus GmbH. - 2699-0016. ; 2:2, s. 843-861
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Tidskriftsartikel (refereegranskat)abstract
- Although the concepts of nonuniform sampling (NUS) and non-Fourier spectral reconstruction in multidimensional NMR began to emerge 4 decades ago (Bodenhausen and Ernst, 1981; Barna and Laue, 1987), it is only relatively recently that NUS has become more commonplace. Advantages of NUS include the ability to tailor experiments to reduce data collection time and to improve spectral quality, whether through detection of closely spaced peaks (i.e., “resolution”) or peaks of weak intensity (i.e., “sensitivity”). Wider adoption of these methods is the result of improvements in computational performance, a growing abundance and flexibility of software, support from NMR spectrometer vendors, and the increased data sampling demands imposed by higher magnetic fields. However, the identification of best practices still remains a significant and unmet challenge. Unlike the discrete Fourier transform, non-Fourier methods used to reconstruct spectra from NUS data are nonlinear, depend on the complexity and nature of the signals, and lack quantitative or formal theory describing their performance. Seemingly subtle algorithmic differences may lead to significant variabilities in spectral qualities and artifacts. A community-based critical assessment of NUS challenge problems has been initiated, called the “Nonuniform Sampling Contest” (NUScon), with the objective of determining best practices for processing and analyzing NUS experiments. We address this objective by constructing challenges from NMR experiments that we inject with synthetic signals, and we process these challenges using workflows submitted by the community. In the initial rounds of NUScon our aim is to establish objective criteria for evaluating the quality of spectral reconstructions. We present here a software package for performing the quantitative analyses, and we present the results from the first two rounds of NUScon. We discuss the challenges that remain and present a roadmap for continued community-driven development with the ultimate aim of providing best practices in this rapidly evolving field. The NUScon software package and all data from evaluating the challenge problems are hosted on the NMRbox platform.
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- Zhang, D. Z., et al.
(författare)
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Genomic and phenotypic changes associated with alterations of migratory behaviour in a songbird
- 2022
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 32:2, s. 381-92
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Tidskriftsartikel (refereegranskat)abstract
- The seasonal migration of birds is a fascinating natural wonder. Avian migratory behaviour changes are common and are probably a polygenic process as avian migration is governed by multiple correlated components with a variable genetic basis. However, the genetic and phenotypic changes involving migration changes are poorly studied. Using one annotated near-chromosomal level de novo genome assembly, 50 resequenced genomes, hundreds of morphometric data and species distribution information, we investigated population structure and genomic and phenotypic differences associated with differences in migratory behaviour in a songbird species, Yellow-throated Bunting Emberiza elegans (Aves: Emberizidae). Population genomic analyses reveal extensive gene flow between the southern resident and the northern migratory populations of this species. The hand-wing index is significantly lower in the resident populations than in the migratory populations, indicating reduced flight efficiency of the resident populations. Here, we discuss the possibility that nonmigratory populations may have originated from migratory populations though migration loss. We further infer that the alterations of genes related to energy metabolism, nervous system and circadian rhythm may have played major roles in regulating migration change. Our study sheds light on phenotypic and polygenic changes involving migration change.
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| 6. |
- Liu, B. Y., et al.
(författare)
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Explosive radiation and spatial expansion across the cold environments of the Old World in an avian family
- 2017
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 7:16, s. 6346-6357
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to elucidate the biogeography and speciation patterns in an entire avian family, which shows a complex pattern of overlapping and nonoverlapping geographical distributions, and much variation in plumage, but less in size and structure. We estimated the phylogeny and divergence times for all of the world's species of Prunella based on multiple genetic loci, and analyzed morphometric divergence and biogeographical history. The common ancestor of Prunella was present in the Sino-Himalayan Mountains or these mountains and Central Asia-Mongolia more than 9 million years ago (mya), but a burst of speciations took place during the mid-Pliocene to early Pleistocene. The relationships among the six primary lineages resulting from that differentiation are unresolved, probably because of the rapid radiation. A general increase in sympatry with increasing time since divergence is evident. With one exception, species in clades younger than c. 3.7 my are allopatric. Species that are widely sympatric, including the most recently diverged (2.4 mya) sympatric sisters, are generally more divergent in size/structure than allo-/parapatric close relatives. The distributional pattern and inferred ages suggest divergence in allopatry and substantial waiting time until secondary contact, likely due to competitive exclusion. All sympatrically breeding species are ecologically segregated, as suggested by differences in size/structure and habitat. Colonizations of new areas were facilitated during glacialperiods, followed by fragmentation during interglacials-contrary to the usual view that glacial periods resulted mainly in fragmentations.
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- Qu, C. L., et al.
(författare)
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Activation of mu-opioid receptors in the ventrolateral orbital cortex inhibits the GABAergic miniature inhibitory postsynaptic currents in rats
- 2015
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 592, s. 64-69
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that mu-opioid receptors in the ventrolateral orbital cortex (VLO) are involved in antinociception in tail flick tests and GABAergic neurons or terminals express mu-opioid receptors in the VLO. The current study examined the effect of selective mu-opioid receptor agonist DAMGO on the GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the VLO in rats using the whole-cell patch clamp. The results demonstrated that 5 mu M DAMGO application into the rat VLO slices significantly reduced the GABAergic mIPSCs frequency, without any effect on its amplitude, and this effect of DAMGO was reversed by pretreatment with selective mu-opioid receptor antagonist I i.M CTOP. Importantly, application of CTOP alone into the VLO slices did not produce any effect on the frequency and amplitude of GABAergic mIPSCs. These results indicate a presynaptic effect of mu-opioid receptor activation on the GABAergic neurons in the VLO. The current data suggests that a presynaptic inhibition of the GABA release may contribute to the mu-opioid receptor mediated effects in the VLO and provides novel electrophysiological evidence for the underlying mechanisms of mu-opioid receptors in the VLO. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Qu, X. B., et al.
(författare)
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Accelerated NMR Spectroscopy with Low-Rank Reconstruction
- 2015
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Ingår i: Angewandte Chemie-International Edition. - : Wiley. - 1433-7851. ; 54:3, s. 852-854
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated multi-dimensional NMR spectroscopy is a prerequisite for high-throughput applications, studying short-lived molecular systems and monitoring chemical reactions in real time. Non-uniform sampling is a common approach to reduce the measurement time. Here, a new method for high-quality spectra reconstruction from non-uniformly sampled data is introduced, which is based on recent developments in the field of signal processing theory and uses the so far unexploited general property of the NMR signal, its low rank. Using experimental and simulated data, we demonstrate that the low-rank reconstruction is a viable alternative to the current state-of-the-art technique compressed sensing. In particular, the low-rank approach is good in preserving of low-intensity broad peaks, and thus increases the effective sensitivity in the reconstructed spectra.
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| 9. |
- Wang, Z., et al.
(författare)
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A Sparse Model-Inspired Deep Thresholding Network for Exponential Signal Reconstruction--Application in Fast Biological Spectroscopy
- 2022
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Ingår i: IEEE Transactions on Neural Networks and Learning Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 2162-237X .- 2162-2388. ; 34:10, s. 7578-92
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Tidskriftsartikel (refereegranskat)abstract
- The nonuniform sampling (NUS) is a powerful approach to enable fast acquisition but requires sophisticated reconstruction algorithms. Faithful reconstruction from partially sampled exponentials is highly expected in general signal processing and many applications. Deep learning (DL) has shown astonishing potential in this field, but many existing problems, such as lack of robustness and explainability, greatly limit its applications. In this work, by combining the merits of the sparse model-based optimization method and data-driven DL, we propose a DL architecture for spectra reconstruction from undersampled data, called MoDern. It follows the iterative reconstruction in solving a sparse model to build the neural network, and we elaborately design a learnable soft-thresholding to adaptively eliminate the spectrum artifacts introduced by undersampling. Extensive results on both synthetic and biological data show that MoDern enables more robust, high-fidelity, and ultrafast reconstruction than the state-of-the-art methods. Remarkably, MoDern has a small number of network parameters and is trained on solely synthetic data while generalizing well to biological data in various scenarios. Furthermore, we extend it to an open-access and easy-to-use cloud computing platform (XCloud-MoDern), contributing a promising strategy for further development of biological applications.
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| 10. |
- Zhao, M., et al.
(författare)
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Phylogenetic position of the Wallcreeper Tichodroma muraria
- 2016
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Ingår i: Journal of Ornithology = Journal fur Ornithologie. - : Springer Science and Business Media LLC. - 0021-8375 .- 1439-0361. ; 157:3, s. 913-918
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Tidskriftsartikel (refereegranskat)abstract
- The Wallcreeper Tichodroma muraria is usually placed in a monotypic family or subfamily within the superfamily Certhioidea, with assumed close relationships to Certhia (treecreepers), Sitta (nuthatches) and Salpornis (spotted creepers). Previous studies have suggested that Tichodroma is most closely related to Sitta, alternatively to Salpornis. We analysed the relationships of Tichodroma using two mitochondrial and five nuclear loci. The tree based on concatenated sequences strongly supported a sister relationship between Tichodroma and Sitta, as well as between Salpornis and Certhia. However, species tree analysis (MP-EST) was unable to resolve these relationships, and although the concatenation tree remains the best hypothesis, more data are needed to corroborate this. © 2016, Dt. Ornithologen-Gesellschaft e.V.
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