ALBERT

Description: As the use of next-generation sequencing (NGS) for the Mendelian diseases diagnosis is expanding, the performance of this method has to be improved in order to achieve higher quality. Typically, performance measures are considered to be designed in the context of each application and, therefore, account for a spectrum of clinically relevant variants. We present EphaGen, a new computational methodology for bioinformatics quality control (QC). Given a single NGS dataset in BAM format and a pre-compiled VCF-file of targeted clinically relevant variants it associates this dataset with a single arbiter parameter. Intrinsically, EphaGen estimates the probability to miss any variant from the defined spectrum within a particular NGS dataset. Such performance measure virtually resembles the diagnostic sensitivity of given NGS dataset. Here we present case studies of the use of EphaGen in context of BRCA1/2 and CFTR sequencing in a series of 14 runs across 43 blood samples and 504 publically available NGS datasets. EphaGen is superior to conventional bioinformatics metrics such as coverage depth and coverage uniformity. We recommend using this software as a QC step in NGS studies in the clinical context. Availability: https://github.com/m4merg/EphaGen or https://hub.docker.com/r/m4merg/ephagen.

Description: : Understanding the biology of ageing is an important and complex challenge. Survival experiments are one of the primary approaches for measuring changes in ageing. Here, we present a major update to SurvCurv, a database and online resource for survival data in animals. As well as a substantial increase in data and additions to existing graphical and statistical survival analysis features, SurvCurv now includes extended mathematical mortality modelling functions and survival density plots for more advanced representation of groups of survival cohorts. Availability and implementation: The database is freely available at https://www.ebi.ac.uk/thornton-srv/databases/SurvCurv/ . All data are published under the Creative Commons Attribution License. Contact: matthias.ziehm@ebi.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Description: We present the first results of our search for transiting exoplanet candidates as part of the Kourovka Planet Search (KPS) project. The primary objective of the project is to search for new hot Jupiters which transit their host stars, mainly in the Galactic plane, in the R c magnitude range of 11–14 mag. Our observations were performed with the telescope of the MASTER robotic network, installed at the Kourovka astronomical observatory of the Ural Federal University (Russia), and the Rowe-Ackermann Schmidt Astrograph, installed at the private Acton Sky Portal Observatory (USA). As test observations, we observed three celestial fields of size 2  x  2 deg 2 during the period from 2012 to 2015. As a result, we discovered four transiting exoplanet candidates among the 39 000 stars of the input catalogue. In this paper, we provide the description of the project and analyse additional photometric, spectral, and speckle interferometric observations of the discovered transiting exoplanet candidates. Three of the four transiting exoplanet candidates are most likely astrophysical false positives, while the nature of the fourth (most promising) candidate remains to be ascertained. Also, we propose an alternative observing strategy that could increase the project's exoplanet haul.

Description: We investigate signatures that would be produced in the spectrum and sky distribution of ultra-high energy cosmic rays (UHECR) by a population of the Galactic sources of high-energy protons in the energy range around 1 EeV, i.e. around the diffusive-to-ballistic transition. In this regime, the CR flux has to be calculated numerically. We employ the approach that consists in backtracking anti-protons from Earth through the Galaxy and integrating the source emissivity along the trajectory. This approach makes evident two generic features of the transition region: sharp increase of the total flux as the energy decreases across the transition region, and its strong anisotropy (appearance of a bright compact spot) all the way until the onset of the diffusive regime. We then discuss and compare several methods to experimentally detect or constrain these features. We find that a few per cent admixture of the Galactic protons can in principle be detected by the current UHECR experiments.

Description: We report the first search for new star clusters performed using the VISTA near-infrared YJK s Magellanic Clouds survey (VMC) data sets. We chose a pilot field of ~0.4 deg 2 located in the South-west of the Small Magelllanic Cloud bar, where the star field is among the densest and highest reddened region in the galaxy. In order to devise an appropriate automatic procedure we made use of dimensions and stellar densities observed in the VMC data sets of the known clusters in this area. We executed different kernel density estimations over a sample of more than 358 000 stars with magnitudes measured in the three YJK s filters. We analysed the new cluster candidates whose colour–magnitude diagrams (CMDs), cleaned from field star contamination, were used to assess the clusters’ reality and estimate reddenings and ages of the genuine systems. As a result 38 objects ( a 55 per cent increase in the known star clusters located in the surveyed field) of 0.15–0.40 arcmin (2.6–7.0 pc) in radius resulted to have near-infrared CMD features which resemble those of star clusters of young to moderate intermediate age (log( t  yr –1 ) ~7.5–9.0). Most of the new star cluster candidates are hardly recognizable in optical images without the help of a sound star field decontaminated CMD analysis. For highly reddened star cluster candidates ( E ( B – V ) ≥ 0.6 mag) the VMC data sets were necessary in order to recognize them.

Description: We determine the response of a uniformly rotating star to tidal perturbations due to a companion. General periodic orbits and parabolic flybys are considered. We evaluate energy and angular momentum exchange rates as a sum of contributions from normal modes allowing for dissipative processes. We consider the case when the response is dominated by the contribution of an identifiable regular spectrum of low-frequency modes, such as rotationally modified gravity modes. We evaluate this response in the limit of very weak dissipation, where individual resonances can be significant and also when dissipative effects are strong enough to prevent wave reflection from the neighbourhood of either the stellar surface or stellar centre, making radiation conditions more appropriate. The former situation may apply to Sun-like stars with radiative cores and convective envelopes and the latter to more massive stars with convective cores and radiative envelopes. We provide general expressions for transfer of energy and angular momentum that can be applied to an orbit with any eccentricity. Detailed calculations require knowledge of the mode spectrum and evaluation of the mode overlap integrals that measure the strength of the tidal interaction. These are evaluated for Sun-like stars in the slow rotation regime where centrifugal distortion is neglected in the equilibrium and the traditional approximation is made for the normal modes. We use both a Wentzel-Kramers-Brillouin-Jeffreys (WKBJ) procedure and a direct numerical evaluation which are found to be in good agreement for regimes of interest. The former is used to provide expressions for the mode spectrum and overlap integrals as a function of mode frequency and stellar rotation rate. These can be used to find the tidal energy and angular momentum exchange rates and hence the orbital evolution. Finally we use our formalism to determine the evolution time scales for an object, in an orbit of small eccentricity, around a Sun-like star in which the tidal response is assumed to occur. Systems with either no rotation or synchronous rotation are considered. Only rotationally modified gravity modes are taken into account under the assumption that wave dissipation proceeds close to the stellar centre. It is noted that inertial waves excited in the convective envelope may produce a comparable amount of tidal dissipation in the latter case for sufficiently large orbital periods.

Description: DNA methylation is one of the most important epigenetic alterations involved in the control of gene expression. Bisulfite sequencing of genomic DNA is currently the only method to study DNA methylation patterns at single-nucleotide resolution. Hence, next-generation sequencing of bisulfite-converted DNA is the method of choice to investigate DNA methylation profiles at the genome-wide scale. Nevertheless, whole genome sequencing for analysis of human methylomes is expensive, and a method for targeted gene analysis would provide a good alternative in many cases where the primary interest is restricted to a set of genes. Here, we report the successful use of a custom Agilent SureSelect Target Enrichment system for the hybrid capture of bisulfite-converted DNA. We prepared bisulfite-converted next-generation sequencing libraries, which are enriched for the coding and regulatory regions of 174 ADME genes (i.e. genes involved in the metabolism and distribution of drugs). Sequencing of these libraries on Illumina’s HiSeq2000 revealed that the method allows a reliable quantification of methylation levels of CpG sites in the selected genes, and validation of the method using pyrosequencing and the Illumina 450K methylation BeadChips revealed good concordance.

Description: 〈span〉〈div〉SUMMARY〈/div〉Guided waves in a water layer overlaying an elastic half-space are known as normal modes. They are often present in seismic recordings at long offsets in shallow-water environment and generally considered coherent noise. The normal modes, however, carry important information about the near-surface and, as demonstrated by a number of authors, can be used to obtain the shallow velocity model. There is a growing evidence that the latter needs not to be isotropic due to various geological reasons. Motivated by that, we consider the normal-mode propagation in case the elastic half-space exhibits orthorhombic anisotropy. We derive the period equation that describes the normal-mode phase velocity dispersion. To simplify the complicated expression, we present acoustic and ellipsoidal orthorhombic approximations. We also outline the approach towards the group velocity and group azimuth calculation and apply it to the ellipsoidal case to obtain concise and intuitive expressions. Using numerical test, we study the relation between phase and group domains in elastic orthorhombic case. The deviation between velocities and azimuths in these domains is the strongest for low frequencies and it rapidly decreases with increasing frequency. For higher frequencies, the anisotropy effects of the underlaying half-space are barely detectable since the observed signal is composed mainly of the direct acoustic wave, resulting in the two domains being nearly indistinguishable.〈/span〉

Description: We present a dynamical analysis of the galaxy cluster AC114 based on a catalogue of 524 velocities. Of these, 169 (32 per cent) are newly obtained at European Southern Observatory (Chile) with the Very Large Telescope and the VIsible MultiObject spectrograph. Data on individual galaxies are presented and the accuracy of the measured velocities is discussed. Dynamical properties of the cluster are derived. We obtain an improved mean redshift value z  = 0.31665 ± 0.0008 and velocity dispersion $\sigma = 1893^{+73}_{-82}\ {\rm km\,s^{-1}}$ . A large velocity dispersion within the core radius and the shape of the infall pattern suggests that this part of the cluster is in a radial phase of relaxation with a very elongated radial filament spanning 12 000 km s –1 . A radial foreground structure is detected within the central 0.5  h –1  Mpc radius, recognizable as a redshift group at the same central redshift value. We analyse the colour distribution for this archetype Butcher–Oemler galaxy cluster and identify the separate red and blue galaxy sequences. The latter subset contains 44 per cent of confirmed members of the cluster, reaching magnitudes as faint as R f = 21.1 (1.0 mag fainter than previous studies). We derive a mass M 200  = (4.3 ± 0.7)  x 10 15 M   h –1 . In a subsequent paper, we will utilize the spectral data presented here to explore the mass–metallicity relation for this intermediate redshift cluster.

Description: To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.