P-Multigrid expansion of hybrid multilevel solvers for discontinuous Galerkin finite element discrete ordinate (DG-FEM-SN) diffusion synthetic acceleration (DSA) of radiation transport algorithms

Effective preconditioning of neutron diffusion problems is necessary for the development of efficient DSA schemes for neutron transport problems. This paper uses P-multigrid techniques to expand two preconditioners designed to solve the MIP diffusion neutron diffusion equation with a discontinuous Galerkin (DG-FEM) framework using first-order elements. These preconditioners are based on projecting the first-order DG-FEM formulation to either a linear continuous or a constant discontinuous FEM system. The P-multigrid expansion allows the preconditioners to be applied to problems discretised with second and higher-order elements. The preconditioning algorithms are defined in the form of both a V-cycle and W-cycle and applied to solve challenging neutron diffusion problems. In addition a hybrid preconditioner using P-multigrid and AMG without a constant or continuous coarsening is used. Their performance is measured against a computationally efficient standard algebraic multigrid preconditioner. The results obtained demonstrate that all preconditioners studied in this paper provide good convergence with the continuous method generally being the most computationally efficient. In terms of memory requirements the preconditioners studied significantly outperform the AMG

Scalable angular adaptivity for Boltzmann transport

This paper describes an angular adaptivity algorithm for Boltzmann transport applications which for the first time shows evidence of $\mathcal{O}(n)$ scaling in both runtime and memory usage, where $n$ is the number of adapted angles. This adaptivity uses Haar wavelets, which perform structured $h$-adaptivity built on top of a hierarchical P$_0$ FEM discretisation of a 2D angular domain, allowing different anisotropic angular resolution to be applied across space/energy. Fixed angular refinement, along with regular and goal-based error metrics are shown in three example problems taken from neutronics/radiative transfer applications. We use a spatial discretisation designed to use less memory than competing alternatives in general applications and gives us the flexibility to use a matrix-free multgrid method as our iterative method. This relies on scalable matrix-vector products using Fast Wavelet Transforms and allows the use of traditional sweep algorithms if desired

Angular adaptivity with spherical harmonics for Boltzmann transport

This paper describes an angular adaptivity algorithm for Boltzmann transport applications which uses Pn and filtered Pn expansions, allowing for different expansion orders across space/energy. Our spatial discretisation is specifically designed to use less memory than competing DG schemes and also gives us direct access to the amount of stabilisation applied at each node. For filtered Pn expansions, we then use our adaptive process in combination with this net amount of stabilisation to compute a spatially dependent filter strength that does not depend on a priori spatial information. This applies heavy filtering only where discontinuities are present, allowing the filtered Pn expansion to retain high-order convergence where possible. Regular and goal-based error metrics are shown and both the adapted Pn and adapted filtered Pn methods show significant reductions in DOFs and runtime. The adapted filtered Pn with our spatially dependent filter shows close to fixed iteration counts and up to high-order is even competitive with P0 discretisations in problems with heavy advection.Comment: arXiv admin note: text overlap with arXiv:1901.0492

Goal-based angular adaptivity for Boltzmann transport in the presence of ray-effects

Boltzmann transport problems often involve heavy streaming, where particles propagate long distance due to the dominance of advection over particle interaction. If an insufficiently refined non-rotationally invariant angular discretisation is used, there are areas of the problem where no particles will propagate. These “ray-effects” are problematic for goal-based error metrics with angular adaptivity, as the metrics in the pre-asymptotic region will be zero/incorrect and angular adaptivity will not occur. In this work we use low-order filtered spherical harmonics, which are rotationally invariant and hence not subject to ray-effects, to “bootstrap” our error metric and enable highly refined anisotropic angular adaptivity with a Haar wavelet angular discretisation. We test this on three simple problems with pure streaming in which traditional error metrics fail. We show our method is robust and produces adapted angular discretisations that match results produced by fixed a priori refinement with either reduced runtime or a constant additional cost even with angular refinement

Hybrid multi-level solvers for discontinuous Galerkin finite element discrete ordinate (DG-FEM-SN) diffusion synthetic acceleration (DSA) of radiation transport algorithms

his paper examines two established preconditioners which were developed to accelerate the solution of discontinuous Galerkin nite element method (DG- FEM) discretisations of the elliptic neutron di usion equation. They are each presented here as a potential way to accelerate the solution of the Modi ed In- terior Penalty (MIP) form of the discontinuous di usion equation, for use as a di usion synthetic acceleration (DSA) of DG-FEM discretisations of the neutron transport equation. The preconditioners are both two-level schemes, di ering in the low-level space utilised. Once projected to the low-level space a selection of algebraic multigrid (AMG) preconditioners are utilised to obtain a further correction step, these are therefore \hybrid" preconditioners. The rst precon- ditioning scheme utilises a continuous piece-wise linear nite element method (FEM) space, while the second uses a discontinuous piece-wise constant space. Both projections are used alongside an element-wise block Jacobi smoother in order to create a symmetric preconditioning scheme which may be used along- side a conjugate gradient algorithm. An eigenvalue analysis reveals that both should aid convergence but the piece-wise constant based method struggles with some of the smoother error modes. Both are applied to a range of problems in- cluding some which are strongly heterogeneous. In terms of conjugate gradient (CG) iterations needed to reach convergence and computational time required, both methods perform well. However, the piece-wise linear continuous scheme appears to be the more e ective of the two. An analysis of computer memory usage found that that the discontinuous piece-wise constant method had the lowest memory requirements

A comparison of element agglomeration algorithms for unstructured geometric multigrid

This paper compares the performance of seven different element agglomeration algorithms on unstructured triangular/tetrahedral meshes when used as part of a geometric multigrid. Five of these algorithms come from the literature on AMGe multigrid and mesh partitioning methods. The resulting multigrid schemes are tested matrix-free on two problems in 2D and 3D taken from radiation transport applications; one of which is in the diffusion limit. In two dimensions all coarsening algorithms result in multigrid methods which perform similarly, but in three dimensions aggressive element agglomeration performed by METIS produces the shortest runtimes and multigrid setup times

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease