The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

In nanopore sequencing devices, electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine (5-mC). Here we quantified the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. By using synthetically methylated DNA, we were able to train a hidden Markov model to distinguish 5-mC from unmethylated cytosine. We applied our method to sequence the methylome of human DNA, without requiring special steps for library preparation.

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 ͑NS͒. The perturbations are initialized with only short wavelength modes so that the self-similar evolution ͑i.e., bubble diameter D b ϰamplitude h b) occurs solely by the nonlinear coupling ͑merger͒ of saturated modes. After an initial transient, it is found that h b ϳ␣ b Agt 2 , where AϭAtwood number, gϭacceleration, and tϭtime. The NS yield D b ϳh b /3 in agreement with experiment but the simulation value ␣ b ϳ0.025Ϯ0.003 is smaller than the experimental value ␣ b ϳ0.057Ϯ0.008. By analyzing the dominant bubbles, it is found that the small value of ␣ b can be attributed to a density dilution due to fine-scale mixing in our NS without interface reconstruction ͑IR͒ or an equivalent entrainment in our NS with IR. This may be characteristic of the mode coupling limit studied here and the associated ␣ b may represent a lower bound that is insensitive to the initial amplitude. Larger values of ␣ b can be obtained in the presence of additional long wavelength perturbations and this may be more characteristic of experiments. Here, the simulation data are also analyzed in terms of bubble dynamics, energy balance and the density fluctuation spectra.

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High-resolution X-ray observations have revealed cavities and ''cold fronts'' with sharp edges in temperature and density 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; the layer's strength is set by a competition between ''plowing up'' and slipping around of field lines, and depends primarily on the ram pressure seen by the moving object. In this inherently three-dimensional problem, our analytic arguments and numerical experiments show that this layer modifies the dynamics of a plunging core, greatly modifying the hydrodynamic instabilities and mixing, changing the geometry of stripped material, and slowing the core through magnetic tension. We derive an expression for the maximum magnetic field strength and thickness of the layer, as well as for 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. The intermittent amplification of the magnetic field as well as the injection of magnetohydrodynamic 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 complex gas-dynamical processes of the intracluster medium and apply quite generally to motions through other magnetized environments, e.g., the interstellar medium.

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 ApJ

Context. Simulations of astrophysical turbulence have reached such a level of sophistication that quantitative results are now starting to emerge. However, contradicting results have been reported in the literature with respect to the performance of the numerical techniques employed for its study and their relevance to the physical systems modelled. Aims. We aim at characterising the performance of a variety of hydrodynamics codes including different particle-based and grid-based techniques on the modelling of decaying supersonic turbulence. This is the first such large-scale comparison ever conducted. Methods. We modelled driven, compressible, supersonic, isothermal turbulence with an rms Mach number of M rms ∼ 4, and then let it decay in the absence of gravity, using runs performed with four different grid codes (ENZO, FLASH, TVD, ZEUS) and three different SPH codes (GADGET, PHANTOM, VINE). We additionally analysed two calculations denoted as PHANTOM A and PHANTOM B using two different implementations of artificial viscosity in PHANTOM. We analysed the results of our numerical experiments using volumeaveraged quantities like the rms Mach number, volume-and density-weighted velocity Fourier spectrum functions, and probability distribution functions of density, velocity, and velocity derivatives. Results. Our analysis indicates that grid codes tend to be less dissipative than SPH codes, though details of the techniques used can make large differences in both cases. For example, the Morris & Monaghan viscosity implementation for SPH results in less dissipation (PHANTOM B and VINE versus GADGET and PHANTOM A). For grid codes, using a smaller diffusion parameter leads to less dissipation, but results in a larger bottleneck effect (our ENZO versus FLASH runs). As a general result, we find that by using a similar number of resolution elements N for each spatial direction means that all codes (both grid-based and particle-based) show encouraging similarity of all statistical quantities for isotropic supersonic turbulence on spatial scales k N/32 (all scales resolved by more than 32 grid cells), while scales smaller than that are significantly affected by the specific implementation of the algorithm for solving the equations of hydrodynamics. At comparable numerical resolution (N particles ≈ N cells ), the SPH runs were on average about ten times more computationally intensive than the grid runs, although with variations of up to a factor of ten between the different SPH runs and between the different grid runs. Conclusions. At the resolutions employed here, the ability to model supersonic to transonic flows is comparable across the various codes used in this study.

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