| 1. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 2. |
- Li, Qishuang, et al.
(författare)
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Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast
- 2024
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Ingår i: Journal of Integrative Plant Biology. - 1672-9072 .- 1744-7909. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A- and D-rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)-glaziovine, (S)-glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.
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| 3. |
- Dai, Juncheng, et al.
(författare)
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Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:10, s. 2855-2864
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung ncer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant netic polymorphisms in the human genome. INDELs are highly associated with multiple human seases, including lung cancer. However, limited studies with large-scale samples have been available to stematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta- alysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional notations were performed to further explore the potential function of lung cancer risk INDELs. nditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci re identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 x 10(- ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 x 10(-7); 12p13.31: rs71450133, Deletion, OR = 09, p = 8.83 x 10(-7); and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 x 10(-8)). The eQTL alysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by gulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, e INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be tentially functional genetic variants for lung cancer risk. Further functional experiments are needed to tter understand INDEL mechanisms in carcinogenesis.
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| 4. |
- Fu, Keren, 1988, et al.
(författare)
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Adaptive Multi-Level Region Merging for Salient Object Detection
- 2014
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Ingår i: British Machine Vision Conference (BMVC) 2014. ; , s. 11 -
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Konferensbidrag (refereegranskat)abstract
- Most existing salient object detection algorithms face the problem of either under or over-segmenting an image. More recent methods address the problem via multi-level segmentation. However, the number of segmentation levels is manually predetermined and only works well on specific class of images. In this paper, a new salient object detection scheme is presented based on adaptive multi-level region merging. A graph based merging scheme is developed to reassemble regions based on their shared contourstrength. This merging process is adaptive to complete contours of salient objects that can then be used for global perceptual analysis, e.g., foreground/ground separation. Such contour completion is enhanced by graph-based spectral decomposition. We show that even though simple region saliency measurements are adopted for each region, encouraging performance can be obtained after across-level integration. Experiments by comparing with 13 existing methods on three benchmark datasets including MSRA-1000, SOD and SED show the proposed method results in uniform object enhancement and achieves state-of-the-art performance.
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| 5. |
- Li, Jingyi, et al.
(författare)
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Cis-acting mutation affecting GJA5 transcription is underlying the Melanotic within-feather pigmentation pattern in chickens
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:41
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Tidskriftsartikel (refereegranskat)abstract
- Melanotic (Ml) is a mutation in chickens that extends black (eumelanin) pigmentation in normally brown or red (pheomelanin) areas, thus affecting multiple within-feather patterns [J. W. Moore, J. R. Smyth Jr, J. Hered. 62, 215-219 (1971)]. In the present study, linkage mapping using a back-cross between Dark Cornish (Ml/Ml) and Partridge Plymouth Rock (ml(+)/ml(+)) chickens assigned Ml to an 820-kb region on chromosome 1. Identity-by-descent mapping, via whole-genome sequencing and diagnostic tests using a diverse set of chickens, refined the localization to the genomic region harboring GJA5 encoding gap-junction protein 5 (alias connexin 40) previously associated with pigmentation patterns in zebrafish. An insertion/deletion polymorphism located in the vicinity of the GJA5 promoter region was identified as the candidate causal mutation. Four different GJA5 transcripts were found to be expressed in feather follicles and at least two showed differential expression between genotypes. The results showed that Melanotic constitutes a cis-acting regulatory mutation affecting GJA5 expression. A recent study established the melanocortin-1 receptor (MC1R) locus and the interaction between the MC1R receptor and its antagonist agoutisignaling protein as the primary mechanism underlying variation in within-feather pigmentation patterns in chickens. The present study advances understanding the mechanisms underlying variation in plumage color in birds because it demonstrates that the activity of connexin 40/GJA5 can modulate the periodic pigmentation patterns within individual feathers.
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| 6. |
- Lv, Zhihan, et al.
(författare)
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Advanced Human–Computer Interaction Technology in Digital Twins
- 2023
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Ingår i: Studies in Computational Intelligence. - 1860-949X .- 1860-9503. ; , s. 99-123
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Bokkapitel (refereegranskat)abstract
- To explore the application of Human–Computer Interaction (HCI) in industrial Digital Twins (DTs), the current application status of DTs in Intelligent Manufacturing (IM) and the HCI problem in human–computer assembly are explored; aiming at the Human Action Recognition (HAR) of machine perspective in human–computer assembly, it proposes the Human Pose Estimation (HPE) method based on improved HRNet and inroduces the attention mechanism to establish the SE_NewHRNet model for the optimization of HPE; in addition, it points out Adaptive Architecture of Deep Learning Based on Confrontation (ADLC), and performs case analysis for the performance verification of the model. The accuracy of SE_NewHRNet in $$\mathrm{A}{P}:{pose}$$ indicator is 75.1%. Compared with other models, its network performance is improved to different extents, the number of parameters and calculation amount are lower, the Loss value decreases rapidly, and the decrease rate becomes slower after 40 iterations. In ADLC, the recognition accuracy of the branch model with three domain discrimination is the highest, reaching 86.50%; in most cases, ADLC performance is better in contrast to other models. Compared with the Wasserstein Generative Adversarial Networks (WGAN) model with the second comprehensive performance, the average accuracy of ADLC is 69.72, 9.24% higher than that of WGAN, and 27.67% higher than that of Source-only. Therefore, the proposed human recognition method performs better.
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| 7. |
- Lv, Zhihan, et al.
(författare)
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Distributed computing to blockchain: Architecture, technology, and applications
- 2023
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Ingår i: Distributed Computing to Blockchain: Architecture, Technology, and Applications. - 9780323961462 ; , s. 39-54
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Bokkapitel (refereegranskat)abstract
- This chapter aims to explore the correlation between distributed computing and blockchain technology and deeply investigate the architecture and application of blockchain technology. Mobile devices are taken as the research object, and blockchain technology is used to provide a distributed computing model for mobile terminals in the wireless communication scenario. Besides, deep learning is employed to classify tasks and enhance the analysis efficiency of multisource data. Finally, a distributed deep learning network model based on blockchain technology is constructed. In addition, the performance of the model is verified by simulation experiments. The experimental results demonstrate that through the comparative analysis of system performance, the computational overhead of the model constructed here is the lowest, maintained at about 0.12s, and the comprehensive income and system operation efficiency are the highest. In terms of the security performance of data transmission, the average delay of the distributed framework reported here is stable at about 250ms, and the identification accuracy of transmitted data reaches 92.40%. Therefore, the distributed deep learning model proposed here realizes splendid recognition accuracy, comprehensive income, and system operation efficiency and shows excellent system performance, which can provide a reference for the improvement of blockchain technology application in future.
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| 8. |
- Niu, Jingyi, et al.
(författare)
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Quantification of Long-Range Dependence in Hydroclimatic Time Series: A Method-Comparison Study
- 2023
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Ingår i: Journal of Applied Meteorology and Climatology. - 1558-8424 .- 1558-8432. ; 62:12, s. 1921-1942
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Tidskriftsartikel (refereegranskat)abstract
- Accurate evaluation of the long-range dependence in hydroclimatic time series is important for understanding its inherent characteristics. However, the reliability of its evaluation may be questioned, since different methods may yield various outcomes. In this study, we evaluate the performances of seven widely used methods for estimating long-range dependence: absolute moment estimation, difference variance estimation, residuals variance estimation, rescaled range estimation, periodogram estimation, wavelet estimation (WLE), and discrete second derivative estimation (DSDE). We examine the influences of six major factors: data length, mean value, three nonstationary components (trend, jump, and periodicity), and one stationary component (short-range dependence). Results from the Monte Carlo experiments show that WLE and DSDE have greater credibility than the other five methods. They also reveal that data length, as well as stationary and nonstationary components, have notable influences on the evaluation of long-range dependence. Following it, we use the WLE and DSDE methods to evaluate the long-range dependence of precipitation during 1961–2015 on the Tibetan Plateau. The results indicate that the precipitation variability mirrors the long-range dependence of the Indian summer monsoon but with obvious spatial difference. This result is consistent with the observations made by previous studies, further confirming the superiority of the WLE and DSDE methods. The outcomes from this study have important implications for modeling and prediction of hydroclimatic time series.
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| 9. |
- Smith, Ryan G., et al.
(författare)
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Apportioning deformation among depth intervals in an aquifer system using InSAR and head data
- 2021
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Ingår i: Hydrogeology Journal. - : Springer Science and Business Media LLC. - 1431-2174 .- 1435-0157. ; 29:7, s. 2475-2486
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Tidskriftsartikel (refereegranskat)abstract
- Land surface subsidence due to excessive groundwater pumping is an increasing concern in California, USA. Interferometric Synthetic Aperture Radar (InSAR) is a remote sensing technique for measuring centimeter-to-millimeter surface deformation at 10–100 m spatial resolution. Here, a data-driven approach that attributes deformation to individual depth intervals within an aquifer system by integrating head data acquired from each of three screened intervals in a monitoring well with InSAR surface deformation measurements was developed. The study area was the Colusa Basin in northern Central Valley. To reconstruct the surface deformation history over the study area, 13 ALOS-PALSAR scenes acquired between 2006 and 2010 were processed. Up to ~3-cm year−1 long-term subsidence and up to ~6 cm seasonal subsidence were observed using the InSAR technique. The technique developed in this paper integrates the InSAR-observed seasonal deformation rate and the co-located head measurements in multiple depth intervals to estimate the elastic skeletal storage coefficient, the time delay between the head change and the observed deformation, and subsequently the deformation of each depth interval. This technique can be implemented when hydraulic head measurements within each depth interval are not correlated with each other. Using this approach, the depth interval that contributed the most to the total subsidence, as well as storage parameters for all intervals, are estimated. The technique can be used for identification of the depth interval within the aquifer system responsible for deformation.
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| 10. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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