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Rapid expansions of bioinformatics and computational biology have broadened the collection and use of -omics data including genomic, transcriptomic, methylomic and a myriad of other health data types, in the clinic and the laboratory. Both clinical and research uses of such data require co-analysis with large datasets, for which participant privacy and the need for data custodian controls must remain paramount. This is particularly challenging in multi-jurisdictional settings, such as Canada, where health privacy and security requirements are often heterogeneous. Data federation presents a solution to this, allowing for integration and analysis of large datasets from various sites while abiding by local policies.The Canadian Distributed Infrastructure for Genomics platform (CanDIG) enables federated querying and analysis of -omics and health data while keeping that data local and under local control. It builds upon existing infrastructures to connect five health and research institutions across Canada, relies heavily on standards and tooling brought together by the Global Alliance for Genomics and Health (GA4GH), implements a clear division of responsibilities among its participants and adheres to international data sharing standards. Participating researchers and clinicians can therefore contribute to and quickly access a critical mass of -omics data across a national network in a manner that takes into account the multi-jurisdictional nature of our privacy and security policies. Through this, CanDIG gives medical and research communities the tools needed to use and analyze the ever-growing amount of -omics data available to them in order to improve our understanding and treatment of various conditions and diseases. CanDIG is being used to make genomic and phenotypic data available for querying across Canada as part of data sharing for five leading pan-Canadian projects including the Terry Fox Comprehensive Cancer Care Centre Consortium Network (TF4CN) and Terry Fox PRecision Oncology For Young peopLE (PROFYLE), and making data from provincial projects such as POG (Personalized Onco- Genomics) more widely available.

The International Cancer Genome Consortium (ICGC)’s Pan-Cancer Analysis of Whole Genomes (PCAWG) project aimed to categorize somatic and germline variations in both coding and non-coding regions in over 2,800 cancer patients. To provide this dataset to the research working groups for downstream analysis, the PCAWG Technical Working Group marshalled ~800TB of sequencing data from distributed geographical locations; developed portable software for uniform alignment, variant calling, artifact filtering and variant merging; performed the analysis in a geographically and technologically disparate collection of compute environments; and disseminated high-quality validated consensus variants to the working groups. The PCAWG dataset has been mirrored to multiple repositories and can be located using the ICGC Data Portal. The PCAWG workflows are also available as Docker images through Dockstore enabling researchers to replicate our analysis on their own data.

In this paper we discuss the effect of recombinations to highly excited states (n > 100) in hydrogen during the cosmological recombination epoch. For this purpose, we developed a new ODE solver for the recombination problem, based on an implicit Gear's method. This solver allows us to include up to 350 l-resolved shells or ~61 000 separate levels in the hydrogen model and to solve the recombination problem for one cosmology in ~27 hours. This is a huge improvement in performance over our previous recombination code, for which a 100-shell computation (5050 separate states) already required ~150 hours on a single processor. We show that for 350 shells down to redshift z ~200 the results for the free electron fraction have practically converged. The final modification in the free electron fraction at z ~200 decreases from about \DeltaNe/Ne ~2.8% for 100 shells to \DeltaNe/Ne ~1.6% for 350 shells. However, the associated changes in the CMB power spectra at large multipoles l are rather small, so that for accurate computations in connection with the analysis of Planck data already ~100 shells are expected to be sufficient. Nevertheless, the total value of \tau could still be affected at a significant level. We also briefly investigate the effect of collisions on the recombination dynamics. With our current estimates for the collisional rates we find a correction of \DeltaNe/Ne ~ -0.088% at z ~ 700, which is mainly caused by l-changing collisions with protons. Furthermore, we present results on the cosmological recombination spectrum, showing that at low frequencies collisional processes are important. However, the current accuracy of collisional rates is insufficient for precise computations of templates for the recombination spectrum at \nu

High-resolution X-ray observations have revealed cavities and `cold fronts' with sharp edges in temperature, density, and metallicity within galaxy clusters. Their presence poses a puzzle since these features are not expected to be hydrodynamically stable, or to remain sharp in the presence of diffusion. However, a moving core or bubble in even a very weakly magnetized plasma necessarily sweeps up enough magnetic field to build up a dynamically important sheath around the object; the layer's strength is set by a competition between `plowing up' of field and field lines slipping around the core. We show that a two-dimensional approach to the problem is quite generally not possible. In three dimensions, we show with analytic arguments and in numerical experiments, that this magnetic layer modifies the dynamics of a plunging core, greatly modifies the effects of hydrodynamic instabilities on the core, modifies the geometry of stripped material, and even slows the fall of the core through magnetic tension. We derive an expression for the maximum magnetic field strength, the thickness of the layer, and the opening angle of the magnetic wake. The morphology of the magnetic draping layer implies the suppression of thermal conduction across the layer, thus conserving strong temperature gradients over the contact surface. The intermittent amplification of the magnetic field as well as the injection of MHD turbulence in the wake of the core is identified to be due to vorticity generation within the magnetic draping layer. These results have important consequences for understanding the physical properties and the complex gasdynamical processes of the intra-cluster medium, and apply quite generally to motions through other magnetized environments, e.g., the ISM., For version of this paper with interactive 3D graphics and full-resolution figures, see http://www.cita.utoronto.ca/~ljdursi/draping/ . 19p, 26 figures, emulateapj format. Version accepted by ApJ - new references, improved figures

We present a study of wind-driven nonlinear interfacial gravity waves using numerical simulations in two dimensions. We consider a case relevant to mixing phenomenon in astrophysical events such as novae in which the density ratio is approximately 1:10. Our physical setup follows the proposed mechanism of Miles [ J. Fluid Mech. 3, 185 (1957) ] for the amplification of such waves. Our results show good agreement with linear predictions for the growth of the waves. We explore how the wind strength affects the wave dynamics and the resulting mixing in the nonlinear stage. We identify two regimes of mixing, namely, the overturning and the cusp-breaking regimes. The former occurs when the wind is strong enough to overcome the gravitational potential barrier and overturn the wave. This result is in agreement with the common notion of turbulent mixing in which density gradients are increased to diffusion scales by the stretching of a series of vortices. In the latter case, mixing is the result of cusp instabilit...

The turbulent Rayleigh–Taylor instability is investigated in the limit of strong mode-coupling using a variety of high-resolution, multimode, three dimensional numerical simulations (NS). The perturbations are initialized with only short wavelength modes so that the self-similar evolution (i.e., bubble diameter Db∝amplitude hb) occurs solely by the nonlinear coupling (merger) of saturated modes. After an initial transient, it is found that hb∼αbAgt2, where A=Atwood number, g=acceleration, and t=time. The NS yield Db∼hb/3 in agreement with experiment but the simulation value αb∼0.025±0.003 is smaller than the experimental value αb∼0.057±0.008. By analyzing the dominant bubbles, it is found that the small value of αb can be attributed to a density dilution due to fine-scale mixing in our NS without interface reconstruction (IR) or an equivalent entrainment in our NS with IR. This may be characteristic of the mode coupling limit studied here and the associated αb may represent a lower bound that is insensiti...

We look in detail at the process of mapping an astrophysical initial model from a stellar evolution code onto the computational grid of an explicit, Godunov type code while maintaining hydrostatic equilibrium. This mapping process is common in astrophysical simulations, when it is necessary to follow short-timescale dynamics after a period of long timescale buildup. We look at the effects of spatial resolution, boundary conditions, the treatment of the gravitational source terms in the hydrodynamics solver, and the initialization process itself. We conclude with a summary detailing the mapping process that yields the lowest ambient velocities in the mapped model., Comment: 59 pages, 21 figures, accepted to ApJS. Some figures are degraded for size constraints

There has been significant recent work which examines a situation where a thin magnetic layer is `draped' over a core merging into a larger cluster; the same process also appears to be at work at a bubble rising from the cluster centre. Such a thin magnetic layer could thermally isolate the core from the cluster medium, but only if the same shear process which generates the layer does not later disrupt it. On the other hand, if the magnetized layer can stabilize against the shear instabilities, then the magnetic layer can have the additional dynamical effect of reducing the shear-driven mixing of the core's material during the merger process. These arguments could equally well to underdense cluster bubbles, which would be even more prone to disruption. While it is well known that magnetic fields can suppress instabilities, it is less clear that a thin layer can suppress instabilities on scales significantly larger than its thickness. Here we consider the stability imparted by a thin magnetized layer. Such a layer can have a significant stabilizing effect even on modes with wavelengths much larger than the thickness of the layer l; to stabilize modes ten times larger requires only that the Alfv\'en speed in the magnetized layer is comparable to the relevant destabilizing velocity -- the shear velocity in the case of pure Kelvin-Helmholtz like instability, or a typical buoyancy velocity in the case of pure Rayleigh-Taylor. We confirm our calculations with two-dimensional numerical experiments using the Athena code., Comment: 20pp, 10 figures; ApJ in press. Please email any comments. v2: Typo in Atwood number definition fixed, and resolution study mentioned. v3: As accepted by ApJ

We consider the competition of the different physical processes that can affect the evolution of a flame bubble in a Type Ia supernovae -- burning, turbulence and buoyancy. Even in the vigorously turbulent conditions of a convecting white dwarf, thermonuclear burning that begins at a point near the center (within 100 km) of the star is dominated by the spherical laminar expansion of the flame, until the burning region reaches kilometers in size. Consequently flames that ignite in the inner ~20 km promptly burn through the center, and flame bubbles anywhere must grow quite large--indeed, resolvable by large-scale simulations of the global system--for significant motion or deformation occur. As a result, any hot-spot that successfully ignites into a flame can burn a significant amount of white dwarf material. This potentially increases the stochastic nature of the explosion compared to a scenario where a simmering progenitor can have small early hot-spots float harmlessly away. Further, the size where the laminar flame speed dominates other relevant velocities sets a characteristic scale for fragmentation of larger flame structures, as nothing--by definition--can easily break the burning region into smaller volumes. This makes possible the development of semi-analytic descriptions of the earliest phase of the propagation of burning in a Type Ia supernovae, which we present here. Our analysis is supported by fully resolved numerical simulations of flame bubbles., 33 pages, 14 figures, accepted for publication in ApJ

We consider potential efficiency gains for time sub-cycling, or time refinement (TR), on Berger-Collela and oct-tree AMR meshes for explicit or local physics (such as explict hydrodynamics), where the work per block is roughly constant with level of refinement. We note that there are generally many more fine zones than there are coarse zones. We then quantify the natural result that any overall efficiency gains from reducing the amount of work on the relatively few coarse zones must necessarily be fairly small. Potential efficiency benefits from TR on these meshes are seen to be quite limited except in the case of refining a small number of points on a large mesh — in this case, the benefit can be made arbitrarily large, albeit at the expense of spatial refinement efficiency.

Many astrophysical systems have important behaviors on scales so disparate that even modern techniques such as adaptive mesh refinement cannot possibly resolve all of the dynamics. However, there are situations where the interactions between the scales are relatively simple; in these cases the system can be meaningfully decomposed into different sub-problems, which can be separately understood and then integrated back together into a large-scale model. Here we describe an in-progress computational astrophysics research program where such an approach is taken for two different problems - that of turbulent mixing in a large-scale flow between a high-speed hot wind and a cold, dense accretion disk; and turbulent ignition in what will become a Type Ia supernovae. In the case of the disk-wind interaction, the turbulent mixing is understood through parameter studies of small-scale mixing flows, with the aim of putting the resulting transport terms into a large-scale wind-disk model. In the case of ignition, the turbulence is itself the large-scale flow, and the ignition physics is the small-scale model which must be understood and inserted parametrically into the large-scale model. In both cases, the detailed modeling of the large number of small-scale models can easily exceed the later cost of the large-scale global computations.

Recent Chandra and XMM-Newton observations of galaxy cluster cooling flows have revealed X-ray emission voids of up to 30 kpc in size that have been identified with buoyant, magnetized bubbles. Motivated by these observations, we have investigated the behavior of rising bubbles in stratified atmospheres using the FLASH adaptive-mesh simulation code. We present results from 2-D simulations with and without the effects of magnetic fields, and with varying bubble sizes and background stratifications. We find purely hydrodynamic bubbles to be unstable; a dynamically important magnetic field is required to maintain a bubble's integrity. This suggests that, even absent thermal conduction, for bubbles to be persistent enough to be regularly observed, they must be supported in large part by magnetic fields. Thermal conduction unmitigated by magnetic fields can dissipate the bubbles even faster. We also observe that the bubbles leave a tail as they rise; the structure of these tails can indicate the history of the dynamics of the rising bubble., 44 pgs, accepted to ApJ. 25 figs; replaced with single-spaced version

Many classical nova ejecta are enriched in CNO and Ne. Rosner et al. recently suggested that the enrichment might originate in the resonant interaction between large-scale shear flows in the accreted H/He envelope and gravity waves at the interface between the envelope and the underlying C/O white dwarf. The shear flow amplifies the waves, which eventually form cusps and break. This wave breaking injects a spray of C/O into the superincumbent H/He. Using two-dimensional simulations, we formulate a quantitative expression for the amount of C/O per unit area that can be entrained into the H/He at saturation. The fraction of the envelope that is enriched depends on the horizontal distribution of shear velocity and the density contrast between the C/O white dwarf and the H/He layer but is roughly independent of the vertical shape of the shear profile. Using this parameterization for the mixed mass, we then perform several one-dimensional Lagrangian calculations of an accreting white dwarf envelope and consider two scenarios: that the wave breaking and mixing is driven by the convective flows; and that the mixing occurs prior to the onset of convection. In the absence of enrichment prior to ignition, the base of the convective zone, as calculated from mixing-length theory with the Ledoux instability criterion, does not reach the C/O interface. As a result, there is no additional mixing, and the runaway is slow. In contrast, the formation of a mixed layer during the accretion of H/He, prior to ignition, causes a more violent runaway. The envelope can be enriched by, 6 pages, 6 figures, uses emulateapj.cls (included); minor changes to text from v1, to appear in ApJ

Critically understanding the `standard candle'-like behavior of Type Ia supernovae requires understanding their explosion mechanism. One family of models for Type Ia Supernovae begins with a deflagration in a Carbon-Oxygen white dwarf which greatly accelerates through wrinkling and flame instabilities. While the planar speed and behavior of astrophysically-relevant flames is increasingly well understood, more complex behavior, such as the flame's response to stretch and curvature, has not been extensively explored in the astrophysical literature; this behavior can greatly enhance or suppress instabilities and local flame-wrinkling, which in turn can increase or decrease the bulk burning rate. In this paper, we explore the effects of curvature on both nuclear flames and simpler model flames to understand the effect of curvature on the flame structure and speed., 25 pages; accepted to ApJ; fixed author fields

We present a case study of validating an astrophysical simulation code. Our study focuses on validating FLASH, a parallel, adaptive-mesh hydrodynamics code for studying the compressible, reactive flows found in many astrophysical environments. We describe the astrophysics problems of interest and the challenges associated with simulating these problems. We describe methodology and discuss solutions to difficulties encountered in verification and validation. We describe verification tests regularly administered to the code, present the results of new verification tests, and outline a method for testing general equations of state. We present the results of two validation tests in which we compared simulations to experimental data. The first is of a laser-driven shock propagating through a multi-layer target, a configuration subject to both Rayleigh-Taylor and Richtmyer-Meshkov instabilities. The second test is a classic Rayleigh-Taylor instability, where a heavy fluid is supported against the force of gravity by a light fluid. Our simulations of the multi-layer target experiments showed good agreement with the experimental results, but our simulations of the Rayleigh-Taylor instability did not agree well with the experimental results. We discuss our findings and present results of additional simulations undertaken to further investigate the Rayleigh-Taylor instability., Comment: 76 pages, 26 figures (3 color), Accepted for publication in the ApJS

We present the results of a simulation of a wind-driven non-linear gravity wave breaking on the surface of a white dwarf. The ``wind'' consists of H/He from an accreted envelope, and the simulation demonstrates that this breaking wave mechanism can produce a well-mixed layer of H/He with C/O from the white dwarf above the surface. Material from this mixed layer may then be transported throughout the accreted envelope by convection, which would enrich the C/O abundance of the envelope as is expected from observations of novae., Comment: 5 pages, 3 figures, to appear in the proceedings of the International Conference on Classical Nova Explosions, Sitges, Spain, 20-24 May 2002

Observed novae abundances and explosion energies estimated from observations indicate that there must be significant mixing of the heavier material of the white dwarf (C+O) into the lighter accreted material (H+He). Accordingly, nova models must incorporate a mechanism that will dredge up the heavier white dwarf material, and fluid motions from an early convection phase is one proposed mechanism. We present results from two-dimensional simulations of classical nova precursor models that demonstrate the beginning of a convective phase during the `simmering' of a Nova precursor. We use a new hydrostatic equilibrium hydrodynamics module recently developed for the adaptive-mesh code FLASH. The two-dimensional models are based on the one-dimensional models of Ami Glasner, and were evolved with FLASH from a pre-convective state to the onset of convection., Comment: 5 pages, 4 figures, from the 2002 International Conference on Classical Novae in Sitges, Spain

We show direct numerical simulations of flame-vortex interactions in order to understand quenching of thermonuclear flames. The key question is—can a thermonuclear flame be quenched? If not, the deflagration-detonation transition mechanisms that demand a finely tuned preconditioned region in the interior of a white dwarf are unlikely to work. In these simulations, we pass a steady-state laminar flame through a vortex pair. The vortex pair represents the most severe strain the flame front will encounter inside the white dwarf. We perform a parameter study, varying the speed and size of the vortex pair, in order to understand the quenching process. No quenching is observed in any of the calculations performed to date.

The Flash code was developed at the University of Chicago as part of the Department of Energy’s Accelerated Strategic Computing Initiative (ASCI). The code was designed specifically to simulate thermonuclear flashes in compact stars (white dwarfs and neutron stars). This paper will give a brief introduction to the astrophysics problems we wish to address, followed by a description of the current version of the Flash code. Finally, we discuss two simulations of astrophysical detonations that we have carried out with the code. The first is of a helium detonation in an X-ray burst. The other simulation models a carbon detonation in a Type Ia supernova explosion.

We present direct numerical simulations of mixing at Rayleigh-Taylor unstable interfaces performed with the FLASH code, developed at the ASCI/Alliances Center for Astrophysical Thermonuclear Flashes at the University of Chicago. We present initial results of single-mode studies in two and three dimensions. Our results indicate that three-dimensional instabilities grow significantly faster than two-dimensional instabilities and that grid resolution can have a significant effect on instability growth rates. We also find that unphysical diffusive mixing occurs at the fluid interface, particularly in poorly resolved simulations., 3 pages, 1 figure. To appear in the proceedings of the 20th Texas Symposium on Relativistic Astrophysics

We discuss some of the computational challenges encountered in simulating the evolution of clusters of galaxies. Eulerian adaptive mesh refinement (AMR) techniques can successfully address these challenges but are currently being used by only a few groups. We describe our publicly available AMR code, FLASH, which uses an object-oriented framework to manage its AMR library, physics modules, and automated verification. We outline the development of the FLASH framework to include collisionless particles, permitting it to be used for cluster simulation., Comment: 3 pages, 3 figures, to appear in Proceedings of the VII International Workshop on Advanced Computing and Analysis Techniques in Physics Research (ACAT 2000), Fermilab, Oct. 16-20, 2000

Cancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic resource to study genetic determinants of somatic mutagenesis across 39 cancer types. Our analyses implicate damaging germline variants in a variety of cancer predisposition and DNA damage response genes with specific somatic mutation patterns. Mutations in the MBD4 DNA glycosylase gene showed association with elevated C>T mutagenesis at CpG dinucleotides, a ubiquitous mutational process acting across tissues. Analysis of somatic structural variation exposed complex rearrangement patterns, involving cycles of templated insertions and tandem duplications, in BRCA1-deficient tumours. Genome-wide association analysis implicated common genetic variation at the APOBEC3 gene cluster with reduced basal levels of somatic mutagenesis attributable to APOBEC cytidine deaminases across cancer types. We further inferred over a hundred polymorphic L1/LINE elements with somatic retrotransposition activity in cancer. Our study highlights the major impact of rare and common germline variants on mutational landscapes in cancer.

We present the results of a numerical study of helium detonations on the surfaces of neutron stars. We describe two-dimensional simulations of the evolution of a detonation as it breaks through the accreted envelope of the neutron star and propagates laterally through the accreted material. The detonation front propagates laterally at nearly the Chapman-Jouguet velocity, v = 1.3 × 109 cm s-1. A series of surface waves propagate across the pool of hot ash behind the detonation front with the same speed, matching the speed expected from shallow water wave theory. The entire envelope oscillates in the gravitational potential well of the neutron star with a period of ~50 μs. The photosphere reaches an estimated height of 10 km above the surface of the neutron star. Our study confirms that such a detonation can insure the spread of burning over the entire neutron star surface on a timescale consistent with burst rise times. We analyze the sensitivity of the results to the spatial resolution and the assumed initial conditions. We conclude by presenting a comparison of this model to type I X-ray bursts.

We present the results of a numerical study on two-dimensional carbon detonations. For an upstream density of 107 g cm-3 the length-to-width ratio of the detonation cells is about 1.6 and is not strongly dependent on the spatial resolution of the simulation. However, the curvature of the weak incident shocks, strength of the triple points and transverse waves, and sizes of the underreacted and overreacted regions all depend strongly on the spatial resolution of the calculation. These resolution studies help define the minimum resolution required by multidimensional Type Ia supernovae models where the cellular structure of a detonation front is a key feature of the model.