11. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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12. |
- Do, Thanh Toan, et al.
(författare)
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Simultaneous feature aggregating and hashing for compact binary code learning
- 2019
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Ingår i: IEEE Transactions on Image Processing. - 1941-0042 .- 1057-7149. ; 28:10, s. 4954-4969
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Tidskriftsartikel (refereegranskat)abstract
- Representing images by compact hash codes is an attractive approach for large-scale content-based image retrieval. In most state-of-the-art hashing-based image retrieval systems, for each image, local descriptors are first aggregated as a global representation vector. This global vector is then subjected to a hashing function to generate a binary hash code. In previous works, the aggregating and the hashing processes are designed independently. Hence, these frameworks may generate suboptimal hash codes. In this paper, we first propose a novel unsupervised hashing framework in which feature aggregating and hashing are designed simultaneously and optimized jointly. Specifically, our joint optimization generates aggregated representations that can be better reconstructed by some binary codes. This leads to more discriminative binary hash codes and improved retrieval accuracy. In addition, the proposed method is flexible. It can be extended for supervised hashing. When the data label is available, the framework can be adapted to learn binary codes which minimize the reconstruction loss with respect to label vectors. Furthermore, we also propose a fast version of the state-of-the-art hashing method Binary Autoencoder to be used in our proposed frameworks. Extensive experiments on benchmark datasets under various settings show that the proposed methods outperform the state-of-the-art unsupervised and supervised hashing methods.
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