ALBERT

Description: Sequence alignment is a long standing problem in bioinformatics. The Basic Local Alignment Search Tool (BLAST) is one of the most popular and fundamental alignment tools. The explosive growth of biological sequences calls for speedup of sequence alignment tools such as BLAST. To this end, we develop high speed BLASTN (HS-BLASTN), a parallel and fast nucleotide database search tool that accelerates MegaBLAST—the default module of NCBI-BLASTN. HS-BLASTN builds a new lookup table using the FMD-index of the database and employs an accurate and effective seeding method to find short stretches of identities (called seeds) between the query and the database. HS-BLASTN produces the same alignment results as MegaBLAST and its computational speed is much faster than MegaBLAST. Specifically, our experiments conducted on a 12-core server show that HS-BLASTN can be 22 times faster than MegaBLAST and exhibits better parallel performance than MegaBLAST. HS-BLASTN is written in C++ and the related source code is available at https://github.com/chenying2016/queries under the GPLv3 license.

Description: Previous formalisms for determining the static perturbation of spherically symmetric self-gravitating elastic Earth models due to displacement dislocations deal with each infinitesimal element of the fault system in its epicentral reference frame. In this work, we overcome this restriction and present novel and compact formulas for obtaining the perturbation due to the whole fault system in an arbitrary and common reference frame. Furthermore, we show that, even in an arbitrary reference frame, it is still possible to discriminate the contributions associated with the polar, bipolar and quadrupolar patterns of the seismic source response, as well as their relation with the along strike, along dip and tensile components of the displacement dislocation. These results allow a better understanding of the relation between the static perturbation and the whole fault system, and find direct applications in geodetic problems, like the modelling of long-wavelength geoid or gravity data from GRACE and GOCE space missions and of the perturbation of the deviatoric inertia tensor of the Earth.

Description: Sensitive instruments like strainmeters and tiltmeters are necessary for measuring slowly varying low amplitude Earth deformations. Nonetheless, laser and fibre interferometers are particularly suitable for interrogating such instruments due to their extreme precision and accuracy. In this paper, a practical design of a simple pendulum borehole tiltmeter based on laser fibre interferometric displacement sensors is presented. A prototype instrument has been constructed using welded borosilicate with a pendulum length of 0.85 m resulting in a main resonance frequency of 0.6 Hz. By implementing three coplanar extrinsic fibre Fabry-Perot interferometric probes and appropriate signal filtering, our instrument provides tilt measurements that are insensitive to parasitic deformations caused by temperature and pressure variations. This prototype has been installed in an underground facility (Rustrel, France) where results show accurate measurements of Earth strains derived from Earth and ocean tides, local hydrologic effects, as well as local and remote earthquakes. The large dynamic range and the high sensitivity of this tiltmeter render it an invaluable tool for numerous geophysical applications such as transient fault motion, volcanic strain and reservoir monitoring.

Description: Model evaluation is a necessary step for better prediction and design of 3D RNA structures. For proteins, this has been widely studied and the knowledge-based statistical potential has been proved to be one of effective ways to solve this problem. Currently, a few knowledge-based statistical potentials have also been proposed to evaluate predicted models of RNA tertiary structures. The benchmark tests showed that they can identify the native structures effectively but further improvements are needed to identify near-native structures and those with non-canonical base pairs. Here, we present a novel knowledge-based potential, 3dRNAscore, which combines distance-dependent and dihedral-dependent energies. The benchmarks on different testing datasets all show that 3dRNAscore are more efficient than existing evaluation methods in recognizing native state from a pool of near-native states of RNAs as well as in ranking near-native states of RNA models.

Description: The geocentre motion is the motion of the centre of mass of the entire Earth, considered an isolated system, in a terrestrial system of reference. We first derive a formula relating the harmonic degree-1 Lagrangian variation of the gravity at a station to both the harmonic degree-1 vertical displacement of the station and the displacement of the whole Earth's centre of mass. The relationship is independent of the nature of the Earth deformation and is valid for any source of deformation. We impose no constraint on the system of reference, except that its origin must initially coincide with the centre of mass of the spherically symmetric Earth model. Next, we consider the geocentre motion caused by surface loading. In a system of reference whose origin is the centre of mass of the solid Earth, we obtain a specific relationship between the gravity variation at the surface, the geocentre displacement and the load Love number $h^{\prime }_1$ , which demands the Earth's structure and rheological behaviour be known. For various networks of real or fictitious stations, we invert synthetic signals of surface gravity variations caused by atmospheric loading to retrieve the degree-1 variation of gravity. We then select six well-distributed stations of the Global Geodynamics Project, which is a world network of superconducting gravimeters, to invert actual gravity data for the degree-1 variations and determine the geocentre displacement between the end of 2004 and the beginning of 2012, assuming it to be due to surface loading. We find annual and semi-annual displacements with amplitude 0.5–2.3 mm.

Description: The goal of pathway analysis is to identify the pathways that are significantly impacted when a biological system is perturbed, e.g. by a disease or drug. Current methods treat pathways as independent entities. However, many signals are constantly sent from one pathway to another, essentially linking all pathways into a global, system-wide complex. In this work, we propose a set of three pathway analysis methods based on the impact analysis, that performs a system-level analysis by considering all signals between pathways, as well as their overlaps. Briefly, the global system is modeled in two ways: (i) considering the inter-pathway interaction exchange for each individual pathways, and (ii) combining all individual pathways to form a global, system-wide graph. The third analysis method is a hybrid of these two models. The new methods were compared with DAVID, GSEA, GSA, PathNet, Crosstalk and SPIA on 23 GEO data sets involving 19 tissues investigated in 12 conditions. The results show that both the ranking and the P -values of the target pathways are substantially improved when the analysis considers the system-wide dependencies and interactions between pathways.

Description: We review the theory of the Earth's elastic and gravitational response to a surface disk load. The solutions for displacement of the surface and the geoid are developed using expansions of Legendre polynomials, their derivatives and the load Love numbers. We provide a matlab  function called diskload that computes the solutions for both uncompensated and compensated disk loads. In order to numerically implement the Legendre expansions, it is necessary to choose a harmonic degree, n max , at which to truncate the series used to construct the solutions. We present a rule of thumb (ROT) for choosing an appropriate value of n max , describe the consequences of truncating the expansions prematurely and provide a means to judiciously violate the ROT when that becomes a practical necessity.

Description: Two types of signals are clearly visible in continuous GPS (cGPS) time-series in Iceland, in particular in the vertical component. The first one is a yearly seasonal cycle, usually sinusoid-like with a minimum in the spring and a maximum in the fall. The second one is a trend of uplift, with higher values the closer the cGPS stations are to the centre of Iceland and ice caps. Here, we study the seasonal cycle signal by deriving its average at 71 GPS sites in Iceland. We estimate the annual and semi-annual components of the cycle in their horizontal and vertical components using a least-squares adjustment. The peak-to-peak amplitude of the cycle of the vertical component at the studied sites ranges from 4 mm near the coastline up to 27 mm at the centre of the Vatnajökull, the largest ice cap in Iceland. The minimum of the seasonal cycle occurs earlier in low lying areas than in the central part of Iceland, consistent with snow load having a large influence on seasonal deformation. Modelling shows that the seasonal cycle is well explained by accounting for elastically induced surface displacements due to snow, atmosphere, reservoir lake and ocean variations. Model displacement fields are derived considering surface loads on a multilayered isotropic spherical Earth. Through forward and inverse modelling, we were able to reproduce a priori information on the average seasonal cycle of known loads (atmosphere, snow in non-glaciated areas and lake reservoir) and get an estimation of other loads (glacier mass balance and ocean). The seasonal glacier mass balance cycle in glaciated areas and snow load in non-glaciated areas are the main contributions to the seasonal deformation. For these loads, induced seasonal vertical displacements range from a few millimetres far from the loads in Iceland, to more than 20 mm at their centres. Lake reservoir load also has to be taken into account on local scale as it can generate up to 20 mm of vertical deformation. Atmosphere load and ocean load are observable and generate vertical displacements in the order of a few millimetres. Inversion results also shows that the Iceland crust is less rigid than the world average. Interannual deviation from the GPS seasonal cycle can occur and are caused by unusual weather conditions over extended period of time.

Description: Bioinformatic analysis often produces large sets of genomic ranges that can be difficult to interpret in the absence of genomic context. Goldmine annotates genomic ranges from any source with gene model and feature contexts to facilitate global descriptions and candidate loci discovery. We demonstrate the value of genomic context by using Goldmine to elucidate context dynamics in transcription factor binding and to reveal differentially methylated regions (DMRs) with context-specific functional correlations. The open source R package and documentation for Goldmine are available at http://jeffbhasin.github.io/goldmine .

Description: CCCTC-binding factor (CTCF) is a multi-functional protein that is assigned various, even contradictory roles in the genome. High-throughput sequencing-based technologies such as ChIP-seq and Hi-C provided us the opportunity to assess the multivalent functions of CTCF in the human genome. The location of CTCF-binding sites with respect to genomic features provides insights into the possible roles of this protein. Here we present the first genome-wide survey and characterization of three important functions of CTCF: enhancer insulator, chromatin barrier and enhancer linker. We developed a novel computational framework to discover the multivalent functions of CTCF based on chromatin state and three-dimensional chromatin architecture. We applied our method to five human cell lines and identified ~46 000 non-redundant CTCF sites related to the three functions. Disparate effects of these functions on gene expression were found and distinct genomic features of these CTCF sites were characterized in GM12878 cells. Finally, we investigated the cell-type specificities of CTCF sites related to these functions across five cell types. Our study provides new insights into the multivalent functions of CTCF in the human genome.