| 1. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
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| 4. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 5. |
- Aceto, Lidia, et al.
(författare)
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Fractional Laplace operator in two dimensions, approximating matrices, and related spectral analysis
- 2020
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Ingår i: Calcolo. - : Springer Science and Business Media LLC. - 0008-0624 .- 1126-5434. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- In this work we review some proposals to define the fractional Laplace operator in two or more spatial variables and we provide their approximations using finite differences or the so-called Matrix Transfer Technique. We study the structure of the resulting large matrices from the spectral viewpoint. In particular, by considering the matrix-sequences involved, we analyze the extreme eigenvalues, we give estimates on conditioning, and we study the spectral distribution in the Weyl sense using the tools of the theory of Generalized Locally Toeplitz matrix-sequences. Furthermore, we give a concise description of the spectral properties when non-constant coefficients come into play. Several numerical experiments are reported and critically discussed.
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| 6. |
- Adriani, Andrea, et al.
(författare)
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Asymptotic Spectra of Large (Grid) Graphs with a Uniform Local Structure (Part I) : Theory
- 2020
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Ingår i: Milan Journal of Mathematics. - : Springer Science and Business Media LLC. - 1424-9286 .- 1424-9294. ; 88:2, s. 409-454
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Tidskriftsartikel (refereegranskat)abstract
- We are mainly concerned with sequences of graphs having a grid geometry, with a uniform local structure in a bounded domain omega subset of Rd, d >= 1. When omega=[0,1] , such graphs include the standard Toeplitz graphs and, for omega=[0,1](d), the considered class includesd-level Toeplitz graphs. In the general case, the underlying sequence of adjacency matrices has a canonical eigenvalue distribution, in the Weyl sense, and we show that we can associate to it a symbol f. The knowledge of the symbol and of its basic analytical features provides many information on the eigenvalue structure, of localization, spectral gap, clustering, and distribution type.Few generalizations are also considered in connection with the notion of generalized locally Toeplitz sequences and applications are discussed, stemming e.g. from the approximation of differential operators via numerical schemes. Nevertheless, more applications can be taken into account, since the results presented here can be applied as well to study the spectral properties of adjacency matrices and Laplacian operators of general large graphs and networks
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| 7. |
- Adriani, Andrea, et al.
(författare)
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Asymptotic spectra of large (grid) graphs with a uniform local structure, Part II : Numerical applications
- 2024
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Ingår i: Journal of Computational and Applied Mathematics. - : Elsevier. - 0377-0427 .- 1879-1778. ; 437
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Tidskriftsartikel (refereegranskat)abstract
- In the current work we are concerned with sequences of graphs having a grid geometry, with a uniform local structure in a bounded domain Ω ⊂ Rd , d ≥ 1. When Ω = [0, 1], such graphs include the standard Toeplitz graphs and, for Ω = [0,1]d, the considered class includes d-level Toeplitz graphs. In the general case, the underlying sequence of adjacency matrices has a canonical eigenvalue distribution, in the Weyl sense, and it has been shown in the theoretical part of this work that we can associate to it a symbol f. The knowledge of the symbol and of its basic analytical features provides key information on the eigenvalue structure in terms of localization, spectral gap, clustering, and global distribution. In the present paper, many different applications are discussed and various numerical examples are presented in order to underline the practical use of the developed theory. Tests and applications are mainly obtained from the approximation of differential operators via numerical schemes such as Finite Differences, Finite Elements, and Isogeometric Analysis. Moreover, we show that more applications can be taken into account, since the results presented here can be applied as well to study the spectral properties of adjacency matrices and Laplacian operators of general large graphs and networks, whenever the involved matrices enjoy a uniform local structure.
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| 8. |
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| 9. |
- Adriani, Andrea, et al.
(författare)
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Generalized Locally Toeplitz matrix-sequences and approximated PDEs on submanifolds : the flat case
- 2023
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Ingår i: Linear and multilinear algebra. - : Informa UK Limited. - 0308-1087 .- 1563-5139. ; , s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- In the present paper, we consider a class of elliptic partial differential equations with Dirichlet boundary conditions where the operator is the Laplace-Beltrami operator Δ over Ω¯, Ω being an open and bounded submanifold of Rν, ν=2,3. We will take into consideration the classical Pk Finite Elements, in the case of Friedrichs-Keller triangulations, leading to sequences of matrices of increasing size. We are interested in carrying out a spectral analysis of the resulting matrix-sequences. The tools for our derivations are mainly taken from the Toeplitz technology and from the rather new theory of Generalized Locally Toeplitz (GLT) matrix-sequences. The current contribution is only quite an initial step, where a general programme is provided, with partial answers leading to further open questions: indeed the analysis is performed on special flat submanifolds and hence there is room for wide generalizations, with a final picture which is still unclear with respect to, e.g. the role of the submanifold curvature.
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