ALBERT

Description: In general, the complex electrical resistivity in the subsurface is anisotropic. Despite this, algorithms for the tomographic inversion of complex resistivity data commonly assume isotropy, mainly due to the lack of anisotropic modelling and inversion schemes, potentially leading to artefacts in the inversion results in the presence of anisotropy. The development of an effective anisotropic complex resistivity inversion algorithm which utilizes the gradient information of some cost function benefits from understanding the characteristics of the problem's sensitivities, that is, the partial derivative of the impedance forward response with respect to the complex conductivities in the different spatial directions, as well as with respect to the different ratios of complex conductivities, that is, the different anisotropy ratios. We here derive expressions for these sensitivities and, based on a 2.5-D finite-element modelling algorithm, we compute and discuss sensitivity distributions as well as measurement response curves of typical surface and cross-borehole measurement configurations for 2-D subsurface anisotropic complex resistivity distributions. Depending on the electrode layout and measurement configuration, the sensitivity with respect to the conductivity in a particular direction shows a unique pattern, while for other directions sensitivity patterns are qualitatively similar. These sensitivity characteristics translate into important equivalences between impedance responses of local anisotropic and isotropic anomalies, for both magnitude and phase. Accordingly, with collinear surface arrays only the complex conductivity in the direction of the electrode layout can be unambiguously resolved, and with cross-borehole arrays only the conductivity in the vertical direction, provided an in-hole current injection is used. Nevertheless, anisotropy ratios involving these resolvable conductivity components are likewise detectable. The distinct shape of the measurement response curves, reflecting the distinct spatial patterns of the corresponding sensitivity distributions, suggest that optimized measurement configurations can be inferred for specific exploration questions involving electrical anisotropy and given electrode layouts. The gained insight into the characteristics of the sensitivity distributions of complex resistivity measurements in case of subsurface anisotropy should guide the implementation of effective anisotropic complex resistivity inversion schemes and lead to a routine use of such schemes in any resistivity and induced polarization surveys whenever subsurface electrical anisotropy could be encountered.

Description: The streaming potential phenomenon is an electrokinetic effect that occurs in porous media. It is characterized by an electrokinetic (EK) coefficient. The aim of this paper is to simulate the EK coefficient in unsaturated conditions using the Lattice Boltzmann method in a 2-D capillary channel. The multiphase flow is simulated with the model of Shan & Chen. The Poisson–Boltzmann equation is solved by implementing the model of Chai & Shi. The streaming potential response shows a non-monotonous behaviour due to the combination of the increase of charge density and decrease of flow velocity with decreasing water saturation. Using a potential of –20 mV at the air–water interface, an enhancement of a factor 5–30 of the EK coefficient, compared to the saturated state, can be observed due to the positive charge excess at this interface which is magnified by the fluid velocity away from the rock surface. This enhancement is correlated to the fractioning of the bubbles, and to the dynamic state of these bubbles, moving or entrapped in the crevices of the channel.

Description: By introducing two types of zenith troposphere delay (ZTD) products in precise point positioning (PPP), we developed the ZTD-corrected PPP and the ZTD-constrained PPP, both of them reduced the PPP convergence time. Both enhanced PPP methods are examined by global empirical ZTD models and regional ZTD corrections. For global ZTD models, we verified that ZTD-corrected PPP will deviate the positioning results, while ZTD-constrained PPP could produce unbiased estimations. Therefore, the latter is utilized to study the performance of global ZTD models (ITG, GPT2w, GZTD and UNB3m). After numerous experiments, we found that the performance of ZTD models was positively related to the real ZTD accuracy, and we proposed a universal tropospheric stochastic model 2SQR(9rms) which denotes double the square of nine times ZTD rms, to constrain ZTD in PPP. The proposed model subsequently was validated by real-time static and kinematic ZTD-constrained PPP on the premise that the ZTD rms on every station was known. Compared with traditional PPP, in static PPP, the number of improved stations is increased by 15.5 per cent (ITG), 14.4 per cent (GPT2w), 11.1 per cent (GZTD) and 8.3 per cent (UNB3m). For kinematic PPP, PPP constrained by ITG model still had the best performance, the number of improved stations is increased by 14.4 per cent, after 30 min of initialization time, 13.4 cm east, 13.4 cm north and 11.7 cm up positioning accuracy was obtained, compared with 15.3 cm east, 15.3 cm north and 14.3 cm up accuracy by traditional PPP. In addition, experiments using regional ZTD corrections to enhance real-time PPP showed that both ZTD-corrected PPP and ZTD-constrained PPP can notably reduce the convergence time on the vertical component (within 15 cm).

Description: Continued advancements in sequencing technologies have fueled the development of new sequencing applications and promise to flood current databases with raw data. A number of factors prevent the seamless and easy use of these data, including the breadth of project goals, the wide array of tools that individually perform fractions of any given analysis, the large number of associated software/hardware dependencies, and the detailed expertise required to perform these analyses. To address these issues, we have developed an intuitive web-based environment with a wide assortment of integrated and cutting-edge bioinformatics tools in pre-configured workflows. These workflows, coupled with the ease of use of the environment, provide even novice next-generation sequencing users with the ability to perform many complex analyses with only a few mouse clicks and, within the context of the same environment, to visualize and further interrogate their results. This bioinformatics platform is an initial attempt at Empowering the Development of Genomics Expertise (EDGE) in a wide range of applications for microbial research.

Description: Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a ‘silver standard’ of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini–Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size.

Description: We study fluctuations in the degree-2 zonal spherical harmonic coefficient of the Earth's gravity potential, C 20 , over the period 2003–2015. This coefficient is related to the Earth's oblateness and studying its temporal variations, C 20 , can be used to monitor large-scale mass movements between high and low latitude regions. We examine C 20 inferred from six different sources, including satellite laser ranging (SLR), GRACE and global geophysical fluids models. We further include estimates that we derive from measured variations in the length-of-day (LOD), from the inversion of global crustal displacements as measured by GPS, as well as from the combination of GRACE and the output of an ocean model as described by Sun et al. We apply a sequence of trend and seasonal moving average filters to the different time-series in order to decompose them into an interannual, a seasonal and an intraseasonal component. We then perform a comparison analysis for each component, and we further estimate the noise level contained in the different series using an extended version of the three-cornered-hat method. For the seasonal component, we generally obtain a very good agreement between the different sources, and except for the LOD-derived series, we find that over 90 per cent of the variance in the seasonal components can be explained by the sum of an annual and semiannual oscillation of constant amplitudes and phases, indicating that the seasonal pattern is stable over the considered time period. High consistency between the different estimates is also observed for the intraseasonal component, except for the solution from GRACE, which is known to be affected by a strong tide-like alias with a period of about 161 d. Estimated interannual components from the different sources are generally in agreement with each other, although estimates from GRACE and LOD present some discrepancies. Slight deviations are further observed for the estimate from the geophysical models, likely to be related to the omission of polar ice and groundwater changes in the model combination we use. On the other hand, these processes do not seem to play an important role at seasonal and shorter timescales, as the sum of modelled atmospheric, oceanic and hydrological effects effectively explains the observed C 20 variations at those scales. We generally obtain very good results for the solution from SLR, and we confirm that this well-established technique accurately tracks changes in C 20 . Good agreement is further observed for the estimate from the GPS inversion, showing that this indirect method is successful in capturing fluctuations in C 20 on scales ranging from intra- to interannual. Obtaining accurate estimates from LOD, however, remains a challenging task and more reliable models of atmospheric wind fields are needed in order to obtain high-quality C 20 , in particular at the seasonal scale. The combination of GRACE data and the output of an ocean model appears to be a promising approach, particularly since corresponding C 20 is not affected by tide-like aliases, and generally gives better results than the solution from GRACE, which still seems to be of rather poor quality.

Description: Joint inversion that simultaneously inverts multiple geophysical data sets to recover a common Earth model is increasingly being applied to exploration problems. Petrophysical data can serve as an effective constraint to link different physical property models in such inversions. There are two challenges, among others, associated with the petrophysical approach to joint inversion. One is related to the multimodality of petrophysical data because there often exist more than one relationship between different physical properties in a region of study. The other challenge arises from the fact that petrophysical relationships have different characteristics and can exhibit point, linear, quadratic, or exponential forms in a crossplot. The fuzzy c-means (FCM) clustering technique is effective in tackling the first challenge and has been applied successfully. We focus on the second challenge in this paper and develop a joint inversion method based on variations of the FCM clustering technique. To account for the specific shapes of petrophysical relationships, we introduce several different fuzzy clustering algorithms that are capable of handling different shapes of petrophysical relationships. We present two synthetic and one field data examples and demonstrate that, by choosing appropriate distance measures for the clustering component in the joint inversion algorithm, the proposed joint inversion method provides an effective means of handling common petrophysical situations we encounter in practice. The jointly inverted models have both enhanced structural similarity and increased petrophysical correlation, and better represent the subsurface in the spatial domain and the parameter domain of physical properties.

Description: Coal seam fires are a worldwide disaster of both ecological and economic importance. Their remote detection from the ground surface or using airborne techniques is required for developing efficient strategies to extinguish them. We investigate here the use of time-domain-induced polarization to localize coal seam fires. For laboratory experiments, we first introduce a modified time-domain-induced polarization methodology to quickly acquire and invert the secondary voltage distribution mapped after the shutdown of the primary current. A set of sandbox experiments is conducted in which coal is embedded into humidified sand. Raw coal alone generates significant induced polarization anomalies, above those shown by the sand. Even higher induced polarization anomalies are detected in presence of a coal seam fire. We postulate that the higher chargeability is due to the pyrolysis, which may enhance electronic polarization or the polarization associated with the cation exchange capacity (CEC) of the material. The position of the coal seam fire is well recovered inside the tank by inverting the secondary voltages in term of a source current density distribution. We also collected field data over a recognized coal seam fire in Colorado, USA. A chargeability anomaly (~800 mV V –1 ) and a resistivity anomaly (~1 Ohm m) are observed at the position of the coal seam fire. We propose a normalized burning front index (a scaled normalized chargeability) to image and localize, without ambiguity, the position of the coal seam fire in the subsurface. The 3-D reconstructed target is located below a negative self-potential anomaly (similarly to what is observed in laboratory experiments) and a temperature anomaly recorded at a depth of 30 cm.

Description: Rock permeability is an important parameter for the formation evaluation. In this paper, a new method with streaming current is proposed to determine the sample permeability based on the electrokinetic effects, and is proved by the experimental measurements. Corresponding to this method, we have designed an experimental setup and a test system, then performed the streaming current (potential) and electro-osmosis pressure experiments with 23 sandstone samples at 0.05 mol l –1 NaCl solution. The streaming current (potential) coefficient and electro-osmosis pressure coefficient are obtained, respectively, with the experimental data at low frequencies with AC lock-in technique. The electrokinetic permeabilities are further calculated with these coefficients. The results are consistent well with the gas permeability measured with Darcy's law, which verifies the current method for estimating rock permeability. Our measurements are also analysed and compared with previous measurements. The results indicate that our method can reflect the essence of electrokinetic effects better and simplify the electrokinetic measurements as well. In addition, we discuss the influences of experimental artefacts (core holder and confining pressure installation) on the electrokinetic data. The results show that the trough phenomenon, appeared in frequency curves of streaming current (potential) coefficients, is induced by the resonance of the core-holder/vibrator system. This is important for the design of electrokinetic setup and the analysis of low-frequency response of the electrokinetic coupling coefficients.

Description: Multiparameter full waveform inversion (FWI) applied to an elastic orthorhombic model description of the subsurface requires in theory a nine-parameter representation of each pixel of the model. Even with optimal acquisition on the Earth surface that includes large offsets, full azimuth, and multicomponent sensors, the potential for trade-off between the elastic orthorhombic parameters are large. The first step to understanding such trade-off is analysing the scattering potential of each parameter, and specifically, its scattering radiation patterns. We investigate such radiation patterns for diffraction and for scattering from a horizontal reflector considering a background isotropic model. The radiation patterns show considerable potential for trade-off between the parameters and the potentially limited resolution in their recovery. The radiation patterns of C 11 , C 22 , and C 33 are well separated so that we expect to recover these parameters with limited trade-offs. However, the resolution of their recovery represented by recovered range of model wavenumbers varies between these parameters. We can only invert for the short wavelength components (reflection) of C 33 while we can mainly invert for the long wavelength components (transmission) of the elastic coefficients C 11 and C 22 if we have large enough offsets. The elastic coefficients C 13 , C 23 , and C 12 suffer from strong trade-offs with C 55 , C 44 , and C 66 , respectively. The trade-offs between C 13 and C 55 , as well as C 23 and C 44 , can be partially mitigated if we acquire P – SV and SV – SV waves. However, to reduce the trade-offs between C 12 and C 66 , we require credible SH – SH waves. The analytical radiation patterns of the elastic constants are supported by numerical gradients of these parameters.

Description: Typically, seismic data are sparsely and irregularly sampled due to limitations in the survey environment and these cause problems for key seismic processing steps such as surface-related multiple elimination or wave-equation-based migration. Various interpolation techniques have been developed to alleviate the problems caused by sparse and irregular sampling. Among many interpolation techniques, matching pursuit interpolation is a robust tool to interpolate the regularly sampled data with large receiver separation such as crossline data in marine seismic acquisition when both pressure and particle velocity data are used. Multicomponent matching pursuit methods generally used the sinusoidal basis function, which have shown to be effective for interpolating multicomponent marine seismic data in the crossline direction. In this paper, we report the use of wavelet basis functions which further enhances the performance of matching pursuit methods for de-aliasing than sinusoidal basis functions. We also found that the range of the peak wavenumber of the wavelet is critical to the stability of the interpolation results and the de-aliasing performance and that the range should be determined based on Nyquist criteria. In addition, we reduced the computational cost by adopting the inner product of the wavelet and the input data to find the parameters of the wavelet basis function instead of using L-2 norm minimization. Using synthetic data, we illustrate that for aliased data, wavelet-based matching pursuit interpolation yields more stable results than sinusoidal function-based one when we use not only pressure data only but also both pressure and particle velocity together.

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: Assigning cancer patients to the most effective treatments requires an understanding of the molecular basis of their disease. While DNA-based molecular profiling approaches have flourished over the past several years to transform our understanding of driver pathways across a broad range of tumors, a systematic characterization of key driver pathways based on RNA data has not been undertaken. Here we introduce a new approach for predicting the status of driver cancer pathways based on signature functions derived from RNA sequencing data. To identify the driver cancer pathways of interest, we mined DNA variant data from TCGA and nominated driver alterations in seven major cancer pathways in breast, ovarian and colon cancer tumors. The activation status of these driver pathways were then characterized using RNA sequencing data by constructing classification signature functions in training datasets and then testing the accuracy of the signatures in test datasets. The signature functions differentiate well tumors with nominated pathway activation from tumors with no signs of activation: average AUC equals to 0.83. Our results confirm that driver genomic alterations are distinctively displayed at the transcriptional level and that the transcriptional signatures can generally provide an alternative to DNA sequencing methods in detecting specific driver pathways.

Description: Modeling the properties and functions of DNA sequences is an important, but challenging task in the broad field of genomics. This task is particularly difficult for non-coding DNA, the vast majority of which is still poorly understood in terms of function. A powerful predictive model for the function of non-coding DNA can have enormous benefit for both basic science and translational research because over 98% of the human genome is non-coding and 93% of disease-associated variants lie in these regions. To address this need, we propose DanQ, a novel hybrid convolutional and bi-directional long short-term memory recurrent neural network framework for predicting non-coding function de novo from sequence. In the DanQ model, the convolution layer captures regulatory motifs, while the recurrent layer captures long-term dependencies between the motifs in order to learn a regulatory ‘grammar’ to improve predictions. DanQ improves considerably upon other models across several metrics. For some regulatory markers, DanQ can achieve over a 50% relative improvement in the area under the precision-recall curve metric compared to related models. We have made the source code available at the github repository http://github.com/uci-cbcl/DanQ .

Description: Molecular sequences in public databases are mostly annotated by the submitting authors without further validation. This procedure can generate erroneous taxonomic sequence labels. Mislabeled sequences are hard to identify, and they can induce downstream errors because new sequences are typically annotated using existing ones. Furthermore, taxonomic mislabelings in reference sequence databases can bias metagenetic studies which rely on the taxonomy. Despite significant efforts to improve the quality of taxonomic annotations, the curation rate is low because of the labor-intensive manual curation process. Here, we present SATIVA, a phylogeny-aware method to automatically identify taxonomically mislabeled sequences (‘mislabels’) using statistical models of evolution. We use the Evolutionary Placement Algorithm (EPA) to detect and score sequences whose taxonomic annotation is not supported by the underlying phylogenetic signal, and automatically propose a corrected taxonomic classification for those. Using simulated data, we show that our method attains high accuracy for identification (96.9% sensitivity/91.7% precision) as well as correction (94.9% sensitivity/89.9% precision) of mislabels. Furthermore, an analysis of four widely used microbial 16S reference databases (Greengenes, LTP, RDP and SILVA) indicates that they currently contain between 0.2% and 2.5% mislabels. Finally, we use SATIVA to perform an in-depth evaluation of alternative taxonomies for Cyanobacteria. SATIVA is freely available at https://github.com/amkozlov/sativa .

Description: DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with ( n = 9) or without ( n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (~90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3'UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5–10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.

Description: Deep sea pockmarks underlain by chimney-like or pipe structures that contain methane hydrate are abundant along the Norwegian continental margin. In such hydrate provinces the interaction between hydrate formation and fluid flow has significance for benthic ecosystems and possibly climate change. The Nyegga region, situated on the western Norwegian continental slope, is characterized by an extensive pockmark field known to accommodate substantial methane gas hydrate deposits. The aim of this study is to detect and delineate both the gas hydrate and free gas reservoirs at one of Nyegga's pockmarks. In 2012, a marine controlled-source electromagnetic (CSEM) survey was performed at a pockmark in this region, where high-resolution 3-D seismic data were previously collected in 2006. 2-D CSEM inversions were computed using the data acquired by ocean bottom electrical field receivers. Our results, derived from unconstrained and seismically constrained CSEM inversions, suggest the presence of two distinctive resistivity anomalies beneath the pockmark: a shallow vertical anomaly at the underlying pipe structure, likely due to gas hydrate accumulation, and a laterally extensive anomaly attributed to a free gas zone below the base of the gas hydrate stability zone. This work contributes to a robust characterization of gas hydrate deposits within subseafloor fluid flow pipe structures.

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: One of the main applications of magnetic field measurements in boreholes is the detection of unexploded ordnance or buried utility structures like pipes or tiebacks. Even though the advantage of fully oriented magnetic vector measurements have long been recognized and could significantly reduce costs and risks, the tools used for those purposes typically measure only the total magnetic field, the vertical and horizontal components or gradients thereof. The Göttingen Bohrloch Magnetometer uses three fibre optic gyros to record its orientation and thus enables us to compute high-quality three-component magnetic vector data regardless of borehole orientation. The measurements described in this paper were run in the scientific borehole Cuxhaven Lüdingworth 1/1A, which was drilled as a part of the ‘Coastal Aquifer Test field’ project to study the dynamics of the saltwater/freshwater interface. As the drill string got stuck during drilling of the first borehole, a second hole was drilled in the immediate vicinity. The drill string lies at a depth between 80 and 114 m at a distance of only 2.5 m southeast of the borehole used for the measurements, making it an ideal target to demonstrate the benefits of vector magnetic surveys. Although the theories to calculate magnetic fields of objects with different shapes is well established and do not need to be tested, they almost exclusively include approximations of the geometry. It is not obvious whether these approximations are suited to describe real data, or whether additional effects or refinements have to be considered. We use both a simplified monopole model and a cylinder model to fit the data and are able to determine the position of the drill string within a statistical error of approximately 10 cm. Additionally, we show that the location of the drill string could not have been determined by measurements of the total field or its horizontal and vertical component alone and that those methods would require the drilling of additional boreholes to obtain an unambiguous result.

Description: The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries.

Description: Single cell RNA-seq experiments provide valuable insight into cellular heterogeneity but suffer from low coverage, 3' bias and technical noise. These unique properties of single cell RNA-seq data make study of alternative splicing difficult, and thus most single cell studies have restricted analysis of transcriptome variation to the gene level. To address these limitations, we developed SingleSplice, which uses a statistical model to detect genes whose isoform usage shows biological variation significantly exceeding technical noise in a population of single cells. Importantly, SingleSplice is tailored to the unique demands of single cell analysis, detecting isoform usage differences without attempting to infer expression levels for full-length transcripts. Using data from spike-in transcripts, we found that our approach detects variation in isoform usage among single cells with high sensitivity and specificity. We also applied SingleSplice to data from mouse embryonic stem cells and discovered a set of genes that show significant biological variation in isoform usage across the set of cells. A subset of these isoform differences are linked to cell cycle stage, suggesting a novel connection between alternative splicing and the cell cycle.

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: The recent super-exponential growth in the amount of sequencing data generated worldwide has put techniques for compressed storage into the focus. Most available solutions, however, are strictly tied to specific bioinformatics formats, sometimes inheriting from them suboptimal design choices; this hinders flexible and effective data sharing. Here, we present CARGO (Compressed ARchiving for GenOmics), a high-level framework to automatically generate software systems optimized for the compressed storage of arbitrary types of large genomic data collections. Straightforward applications of our approach to FASTQ and SAM archives require a few lines of code, produce solutions that match and sometimes outperform specialized format-tailored compressors and scale well to multi-TB datasets. All CARGO software components can be freely downloaded for academic and non-commercial use from http://bio-cargo.sourceforge.net .

Description: Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al . demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/.

Description: Many genomes display high levels of heterozygosity (i.e. presence of different alleles at the same loci in homologous chromosomes), being those of hybrid organisms an extreme such case. The assembly of highly heterozygous genomes from short sequencing reads is a challenging task because it is difficult to accurately recover the different haplotypes. When confronted with highly heterozygous genomes, the standard assembly process tends to collapse homozygous regions and reports heterozygous regions in alternative contigs. The boundaries between homozygous and heterozygous regions result in multiple assembly paths that are hard to resolve, which leads to highly fragmented assemblies with a total size larger than expected. This, in turn, causes numerous problems in downstream analyses such as fragmented gene models, wrong gene copy number, or broken synteny. To circumvent these caveats we have developed a pipeline that specifically deals with the assembly of heterozygous genomes by introducing a step to recognise and selectively remove alternative heterozygous contigs. We tested our pipeline on simulated and naturally-occurring heterozygous genomes and compared its accuracy to other existing tools. Our method is freely available at https://github.com/Gabaldonlab/redundans .

Description: Seismic waves produced by fault ruptures give rise to gravity perturbations. So far, these perturbations have either been modelled as permanent coseismic gravity change in a half-space or spherical Earth model, or as full time-domain model in infinite space. In this paper, we present the explicit solution of gravity perturbations in time domain produced by a double-couple buried in a homogeneous half-space. This result is especially suited to study gravity perturbations up to a few hundreds of kilometres from the epicentre. It facilitates detailed parametric studies of gravity perturbations from fault rupture, and predicts gravity perturbations of real earthquakes with greatly improved accuracy. The results may serve to develop first designs of gravity-assisted earthquake early-warning systems, made possible by a new generation of ultrasensitive gravity gradiometers, which is currently under development.

Description: Continuous gravimetric observations have been made with three successive generations of superconducting gravimeter over 20 yr at Syowa Station ( $39.6\deg$ E, $69.0\deg$ S), East Antarctica. The third-generation instrument, OSG#058, was installed in January 2010 and was calibrated by an absolute gravimeter during January and February, 2010. The estimated scale factor was –73.823 ± 0.053 μGal V –1 (1 μGal = 10 –8 m s –2 ). The first 5 yr of OSG#058 data from 2010 January 7 to 2015 January 10 were decomposed into tidal waves (M3 to Ssa) and other non-tidal components by applying the Bayesian tidal analysis program BAYTAP. Long-term non-tidal gravity residuals, which were obtained by subtracting annual and 18.6 year tidal waves and the predicted gravity response to the Earth's variable rotation, showed significant correlation with the accumulated snow depth measured at Syowa Station. The greatest correlation occurred when the gravity variations lagged the accumulated snow depth by 21 d. To estimate the gravitational effect of the accumulated snow mass, we inferred a conversion factor of 3.13 ± 0.08 μGal m –1 from this relation. The accumulated snow depth at Syowa Station was found to represent an extensive terrestrial water storage (the snow accumulation) around Syowa Station, which was estimated from the Gravity Recovery and Climate Experiment satellite gravity data. The snow accumulation around Syowa Station was detectable by the superconducting gravimeter.

Description: The new release AIUB-RL02 of monthly gravity models from GRACE GPS and K-Band range-rate data is based on reprocessed satellite orbits referring to the reference frame IGb08. The release is consistent with the IERS2010 conventions. Improvements with respect to its predecessor AIUB-RL01 include the use of reprocessed (RL02) GRACE observations, new atmosphere and ocean dealiasing products (RL05), an upgraded ocean tide model (EOT11A), and the interpolation of shallow ocean tides (admittances). The stochastic parametrization of AIUB-RL02 was adapted to include daily accelerometer scale factors, which drastically reduces spurious signal at the 161 d period in C 20 and at other low degree and order gravity field coefficients. Moreover, the correlation between the noise in the monthly gravity models and solar activity is considerably reduced in the new release. The signal and the noise content of the new AIUB-RL02 monthly gravity fields are studied and calibrated errors are derived from their non-secular and non-seasonal variability. The short-period time-variable signal over the oceans, mostly representing noise, is reduced by 50 per cent with respect to AIUB-RL01. Compared to the official GFZ-RL05a and CSR-RL05 monthly models, the AIUB-RL02 stands out by its low noise at high degrees, a fact emerging from the estimation of seasonal variations for selected river basins and of mass trends in polar regions. Two versions of the monthly AIUB-RL02 gravity models, with spherical harmonics resolution of degree and order 60 and 90, respectively, are available for the time period from March 2003 to March 2014 at the International Center for Global Earth Models or from ftp://ftp.unibe.ch/aiub/GRAVITY/GRACE (last accessed 22 March 2016).

Description: We document two kinds of traveling ionospheric disturbances, namely, CTIDs (Co-tsunami-Traveling-Ionospheric-disturbances) and ATIDs (Ahead-of-Tsunami-Traveling-Ionospheric-disturbances) related to the Tohoku-Oki tsunami of 2011 March 11. They are referred to the disturbances that remain behind and ahead of the principal tsunami wave front, respectively. We first note their presence in a numerical experiment performed using a simulation code coupling the tsunami, atmosphere and ionosphere. This code uses the tsunami wavefield as an input and simulates acoustic-gravity waves (AGWs) in the atmosphere and TIDs, in the form of total electron content (TEC) disturbance, in the ionosphere. The simulated TEC reveals the excitation of CTIDs (at about 2 TECU) and ATIDs (at about 1 TECU), representing up to 5 per cent disturbance over the ambient electron density, and they arise from the dissipation of AGWs in the thermosphere. A novel outcome is that during the tsunami passage between ~6° and 12° of epicentral distance, strong ATIDs arrive ~20–60 min ahead of the tsunami wave front covering ~3°–10° of distance from the tsunami location. Simulation results are compared with the far-field observations using GNSS satellites and confirm that ATIDs are the first detected TEC maximum, occurring 20–60 min ahead of the tsunami arrival. Our simulation also confirms the presence of largest TEC maximum representing CTIDs, 10–20 min after the first tsunami wave. ATIDs reported in this study have characteristics that can be potentially used for the early warning of the tsunami.

Description: Although seismic attenuation measurements have great potential to enhance our knowledge of physical conditions and rock properties, their application is limited because robust methods for improving both the resolution and accuracy of attenuation estimates have not yet been established. We propose attenuation estimation methods for zero-offset vertical seismic profile (VSP) data by combining seismic interferometry (SI) and the modified median frequency shift (MMFS) method developed for attenuation estimation using sonic waveform data. The configuration of zero-offset VSP data is redatumed to that of the sonic logging measurement by adopting two types of SI: deconvolution interferometry and crosscorrelation interferometry (CCI). Then, we can apply the MMFS method to the redatumed VSP data. Although the amplitude information estimated from CCI is biased, we propose a correction method for this bias to correctly estimate attenuation. First, to investigate the performance both in resolution and accuracy, we apply different trace separations to synthetic data with random noise at different signal-to-noise ratio levels. Second, we estimate the influence of residual reflection events after wavefield separation on attenuation estimation. The proposed methods provide more stable attenuation estimates in comparison with the spectral ratio method because the mean-median procedure suppresses random events and characteristic features caused by residual reflection events in spectral domain. Our numerical experiments also imply that the proposed methods can estimate scattering attenuation values even if frequency components are not changed between the two receiver depths. Finally, by preliminarily applying the proposed methods to field VSP data, we demonstrate the advantages of the proposed method in the resolution and stability of attenuation estimates and these observations correlate with those of numerical tests.

Description: Capacitively Coupled Resistivity (CCR) is conventionally used to emulate DC resistivity measurements and may provide important information about the ice content of material in periglacial areas. The application of CCR theoretically enables the determination of both electrical parameters, that is, the resistivity and the electrical permittivity, by analysing magnitude and phase shift spectra. The electrical permittivity may dominate the impedance, especially in periglacial areas or regions of hydrogeological interest. However, previous theoretical work suggested that the phase shift may strongly depend on electrode height above ground, implying that electrode height must be known with great accuracy to determine electrical permittivity. Here, we demonstrate with laboratory test measurements, theoretical modelling and by analysing the Jacobian matrix of the inversion that the sensitivity towards electrode height is drastically reduced if the electrical permittivity is frequency dependent in a way that is typical for ice. For the first time, we used a novel broad-band CCR device ‘Chameleon’ for a field test located in one of the ridge galleries beneath the crest of Mount Zugspitze. A permanently ice covered bottom of a tunnel was examined. For the inversion of the measured spectra, the frequency dependence of the electrical parameters was parametrized in three different ways: A Debye Model for pure ices, a Cole–Cole Model for pure ices and a dual Cole–Cole Model including interfacial water additionally. The frequency-dependent resistivity and permittivity spectra obtained from the inversion, including low- and high-frequency limits, agree reasonably well with laboratory and field measurements reported in the literature.

Description: Apparent acceleration in Gravity Recovery and Climate Experiment (GRACE) Antarctic ice mass time-series may reflect both ice discharge and surface mass balance contributions. However, a recent study suggests there is also contamination from errors in atmospheric pressure de-aliasing fields [European Center for Medium-Range Weather Forecast (ECMWF) operational products] used during GRACE data processing. To further examine this question, we compare GRACE atmospheric pressure de-aliasing (GAA) fields with in situ surface pressure data from coastal and inland stations. Differences between the two are likely due to GAA errors, and provide a measure of error in GRACE solutions. Time-series of differences at individual weather stations are fit to four presumed error components: annual sinusoids, a linear trend, an acceleration term and jumps at times of known ECMWF model changes. Using data from inland stations, we estimate that atmospheric pressure error causes an acceleration error of about +7.0 Gt yr –2 , which is large relative to prior GRACE estimates of Antarctic ice mass acceleration in the range of –12 to –14 Gt yr –2 . We also estimate apparent acceleration rates from other barometric pressure (reanalysis) fields, including ERA-Interim, MERRA and NCEP/DOE. When integrated over East Antarctica, the four mass acceleration estimates (from GAA and the three reanalysis fields) vary considerably (by ~2–16 Gt yr –2 ). This shows the need for further effort to improve atmospheric mass estimates in this region of sparse in situ observations, in order to use GRACE observations to measure ice mass acceleration and related sea level change.

Description: We evaluate the applicability and the effectiveness of GPR attribute analysis for high-resolution glacier imaging and characterization, testing this approach on 4-D GPR multifrequency data collected in a small glacier in the Eastern Alps, by repeating the acquisition along the same profiles in four different periods of the year 2013. The main objectives are to image and characterize the glacier's inner structure and to quantitatively monitor the seasonal thawing of near-surface frozen materials (snow/firn). A multiattribute approach is used to characterize the subsurface through different attribute categories, including instantaneous and textural attributes considering not only amplitude-, phase- and frequency-related attributes, but also other more complex and integrated parameters. We combine information from more than one attribute into a single image with composite displays, using overlays or mixed displays. The results demonstrate that the developed GPR attribute analysis can provide significant improvements in the discrimination of GPR signals, and obtain enhanced and more constrained data interpretations.

Description: Migration velocity analysis aims at automatically updating the large-scale components of the velocity model, called macromodel. Extended Common Image Gathers are panels used to evaluate focusing after imaging and are constructed as a function of a spatial shift introduced in the imaging condition. We investigate how transmitted waves can also be used in migration velocity analysis: instead of back-propagating the residuals associated with reflected waves, we propose to back-propagate the full wavefield. The image function, equivalent to the migrated section for reflected data, does not exhibit localized events in space along horizons but is still sensitive to the choice of the background velocity model and can thus be coupled to the same objective function defined in the image domain. In order to enhance the benefits of direct waves, we consider a cross-well configuration. Direct waves provide a large illumination between two vertical wells. Associated Common Image Gathers present different characteristics than the ones associated with reflected waves in surface acquisition. In particular, energy is spread over up to the maximum penetration depth. We invert cross-well seismic data along two lines. In the first case, the input data contain the full wavefield dominated by transmitted waves. It demonstrates the possibility to handle transmitted waves to determine the velocity model. It appears that the misfit in the data domain is largely reduced after inversion. In the second case, we use the same algorithm, but with reflected observed data only, as in a classical approach. Most of velocity updates are localized around the reflectivity, leading to an incorrect final model. This demonstrates the benefit of transmitted waves for migration velocity analysis in a cross-well configuration.

Description: The long-wavelength gravity field contains information about processes in the sublithospheric mantle. As satellite-derived gravity models now provide the long to medium-wavelength gravity field at unprecedented accuracy, techniques used to process gravity data need to be updated. We show that when determining these long-wavelengths, the treatment of topographic-isostatic effect (TIE) and isostatic effects (IE) is a likely source of error. We constructed a global isostatic model and calculated global TIE and IE. These calculations were done for ground stations as well as stations at satellite height. We considered both gravity and gravity gradients. Using these results, we determined how much of the gravity signal comes from distant sources. We find that a significant long-wavelength bias is introduced if far-field effects on the topographic effect are neglected. However, due to isostatic compensation far-field effects of the topographic effect are to a large degree compensated by the far-field IE. This means that far-field effects can be reduced effectively by always considering topographic masses together with their compensating isostatic masses. We show that to correctly represent the ultra-long wavelengths, a global background model should be used. This is demonstrated both globally and for a continental-scale case area in North America. In the case of regional modelling, where the ultra-long wavelengths are not of prime importance, gravity gradients can be used to help minimize correction errors caused by far-field effects.

Description: An integrated approach to interpret Self-Potential (SP) anomalies based on spectral analysis and tomographic methods is presented. The Maximum Entropy Method (MEM) is used for providing accurate estimates of the depth of the anomaly source. The 2-D tomographic inversion technique, based on the underground charge occurrence probability (COP) function, is, then, used to fully characterize the anomalous body, as the MEM is not helpful in delineating the shape of the anomaly source. The proposed integrated approach is applied for the inversion of synthetic SP data generated by geometrically simple anomalous bodies, such as cylinders and inclined sheets. This numerical study has allowed the determination of mathematical relationships between zero lines of the COP distributions, the polarization angles and the positions along the profile of the causative sources, which have been of great help for interpreting the related SP anomalies. Finally, the analysis of field examples shows the high potential applicability of the proposed integrated approach for SP data inversion.

Description: Volcanic and tectonic events are the main processes involved in the generation of the oceanic crust and responsible for the seismicity associated with seafloor spreading. To monitor this activity, usually not or poorly detected by land-based seismological stations, we deployed from February 2012 to February 2013 a network of autonomous hydrophones to compare the behaviour of the ultraslow-spreading Southwest Indian ridge (SWIR) with that of the intermediate-spreading Southeast Indian ridge (SEIR). The rate of seismicity is similar for both ridges, suggesting that there is no systematic relationship between seismicity and spreading rates. The along-axis distribution of the seismic events, however, does differ, reflecting the rate dependence of accretion modes. Earthquakes are sparse and regularly spaced and scattered along the SWIR, reflecting prevailing tectonic processes. By contrast, along the SEIR, events are irregularly distributed and focus at ridge-segment ends and transforms faults, reflecting the ridge segmentation; only two swarms occurred at a segment centre and are probably caused by a magmatic event. This seismicity distribution thus looks controlled by segment-scale crustal heterogeneities along the SEIR and by regional-scale contrasting accretion processes along the SWIR, probably driven by different lithospheric and asthenospheric dynamics on either side of the Melville fracture zone. The comparison of hydroacoustic and teleseismic catalogues shows that, along these spreading ridges, the background seismicity observed in 1 yr by a hydroacoustic network is representative of the seismicity observed over two decades by land-based networks.

Description: Constraining laterally varying structures in planetary interiors is important for understanding both the composition and the internal dynamics of a planet. Recognizing that seismic imaging technique is currently only viable for studying the Earth's interior structures, methods that can be supported by advanced space geodetic techniques may become alternatives to ‘image’ the interiors of other planets. The method of tidal tomography is one possibility, and it relies on high precision measurement of the response of a planet to its body tide. However, it is essential to develop an efficient analytical tool that computes the dependence of tidal response to 3-D interior structures. In this paper, we present a complete formulation of such an analytical tool, which calculates to high accuracy the tidal response of a terrestrial planet with lateral heterogeneities in its elastic and density structures. We treat the lateral heterogeneities as small perturbations and derive the governing equations based on the perturbation theory. In a spherical harmonic representation, equations at each order of perturbation are reduced into multiple matrix equations at harmonics that are allowed by mode couplings, and the total response equals the sum of all those single-harmonic responses, which can be solved semi-analytically. We test our perturbation method by applying it to the Moon with a harmonic degree-1 mantle structure for which the perturbation solutions of the tidal response are compared with those from a fully numerical method. The remarkable agreement between results from these two methods validates the perturbation method. As an example, we then use the perturbation method to evaluate the impact of lunar crustal thickness variations on tidal response of the Moon. We find that lunar crust produces much smaller degree-3 tidal responses than a relatively weak degree-1 structure in the deep lunar mantle. Our calculations show that degree-3 tidal response measurements may hold key constraints on possible degree-1 mantle structure of the Moon, as suggested from previous modelling results.

Description: Seismic data are primarily used in studies of the Earth's lithospheric structure including the Moho geometry. In regions, where seismic data are sparse or completely absent, gravimetric or combined gravimetric-seismic methods could be applied to determine the Moho depth. In this study, we derive and present generalized expressions for solving the Vening Meinesz–Moritz's (VMM) inverse problem of isostasy for a Moho depth determination from gravity and vertical gravity-gradient data. By solving the (non-linear) Fredholm's integral equation of the first kind, the linearized observation equations, which functionally relate the (given) gravity/gravity-gradient data to the (unknown) Moho depth, are derived in the spectral domain. The VMM gravimetric results are validated by using available seismic and gravimetric Moho models. Our results show that the VMM Moho solutions obtained by solving the VMM problem for gravity and gravity-gradient data are almost the same. This finding indicates that in global applications, using the global gravity/gravity-gradient data coverage, the spherical harmonic expressions for the gravimetric forward and inverse modelling yield (theoretically) the same results. Globally, these gravimetric solutions have also a relatively good agreement with the CRUST1.0 and GEMMA GOCE models in terms of their rms Moho differences (4.7 km and 4.1 km, respectively).

Description: Geophysical techniques are widely used to monitor volcanic unrest. A number of studies have also demonstrated that hydrological processes can produce or trigger geophysical signals. Hydrologically induced gravity signals have previously been recorded by specifically designed gravity surveys as well as, inadvertently, by volcano monitoring studies. Water table corrections of microgravity surveys are commonplace. However, the fluctuations of the water table beneath survey locations are often poorly known, and such a correction fails to account for changes in water-mass storage in the unsaturated zone. Here, we combine 2-D axis-symmetrical numerical fluid-flow models with an axis-symmetric, distributed-mass, gravity calculation to model gravity changes in response to fluctuating hydrological recharge. Flow simulations are based on tropical volcanic settings where high surface permeabilities promote thick unsaturated zones. Our study highlights that mass storage (saturation) changes within the unsaturated zone beneath a survey point can generate recordable gravity changes. We show that for a tropical climate, recharge variations can generate gravity variations of over 150 μGal; although, we demonstrate that for the scenarios investigated here, the probability of recording such large signals is low. Our modelling results indicate that microgravity survey corrections based on water table elevation may result in errors of up to 100 μGal. The effect of inter-annual recharge fluctuations dominate over seasonal cycles which makes prediction and correction of the hydrological contribution more difficult. Spatial hydrogeological heterogeneity can also impact on the accuracy of relative gravity surveys, and can even result in the introduction of additional survey errors. The loading fluctuations associated with saturation variations in the unsaturated zone may also have implications for other geophysical monitoring techniques, such as geodetic monitoring of ground deformation.

Description: Several attempts have been made to obtain a radiographic image inside volcanoes using cosmic-ray muons (muography). Muography is expected to resolve highly heterogeneous density profiles near the surface of volcanoes. However, several prior works have failed to make clear observations due to contamination by background noise. The background contamination leads to an overestimation of the muon flux and consequently a significant underestimation of the density in the target mountains. To investigate the origin of the background noise, we performed a Monte Carlo simulation. The main components of the background noise in muography are found to be low-energy protons, electrons and muons in case of detectors without particle identification and with energy thresholds below 1 GeV. This result was confirmed by comparisons with actual observations of nuclear emulsions. This result will be useful for detector design in future works, and in addition some previous works of muography should be reviewed from the view point of background contamination.

Description: Essential to understanding sea level change and its causes during the last interglacial (LIG) is the quantification of uncertainties. In order to estimate the uncertainties, we develop a statistical framework for the comparison of palaeoclimatic sea level index points and GIA model predictions. For the investigation of uncertainties, as well as to generate better model predictions, we implement a massive ensemble approach by applying a data assimilation scheme based on particle filter methods. The different runs are distinguished through varying ice sheet reconstructions based on oxygen-isotope curves and different parameter selections within the GIA model. This framework has several advantages over earlier work, such as the ability to examine either the contribution of individual observations to the results or the probability of specific input parameters. This exploration of input parameters and data leads to a larger range of estimates than previously published work. We illustrate how the assumptions that enter into the statistical analysis, such as the existence of outliers in the observational database or the initial ice volume history, can introduce large variations to the estimate of the maximum highstand. Thus, caution is required to avoid overinterpreting results. We conclude that there are reasonable doubts whether the data sets previously used in statistical analyses are able to tightly constrain the value of maximum highstand during the LIG.

Description: A 3-D density model of the crust and upper mantle beneath the Karoo basin is presented here. The model is constrained using potential field, borehole and seismic data. Uplift of the basin by the end of the Cretaceous has resulted in an unusually high plateau (〉1000 m) covering a large portion of South Africa. Isostatic studies show the topography is largely compensated by changes in Moho depths (~35 km on-craton and 〉45 km off-craton) and changes in lithospheric mantle densities between the Kaapvaal Craton and surrounding regions (~50 kg m –3 increase from on- to off-craton). This density contrast is determined by inverted satellite gravity and gravity gradient data. The highest topography along the edge of the plateau (〉1200 m) and a strong Bouguer gravity low over Lesotho, however, can only be explained by a buoyant asthenosphere with a density decrease of around 40 kg m –3 .

Description: Geothermal well GRT-1 (Rittershoffen, Alsace) was drilled in 2012. Its open-hole section (extending down to a depth of 2.6 km) penetrated fractured sandstones and granite. In 2013, the well was subjected to Thermal, Chemical and Hydraulic (TCH) stimulation, which improved the injectivity index fivefold. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation well-logging (acoustic and temperature [ T ] logs) and mud-logging data. This comparison revealed modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement, and the post-stimulation T logs are important for characterizing this enhancement. Chemical alteration due to mechanical erosion at the tops and bottoms of the fractures was observed in the sandstones. These zones display indications of very small new permeability after the TCH stimulation. Because a major fault zone caved extensively where it crosses the borehole, it was not imaged in the acoustic logs. However, this originally permeable zone was enhanced as demonstrated by the T logs. Based on the natural injectivity of this fault zone, hydraulic erosion and thermal microcracking of its internal quartz veins are associated with this permeability enhancement. Although local changes in the borehole wall observed in the acoustic images cannot be directly linked to the improved injectivity index, the comparison of the acoustic image logs allows for identification of fracture zones impacted by the TCH stimulation.

Description: We investigate the spatial coherence of underwater ambient noise using a yearlong time-series measured off Ascension Island. Qualitative agreement with observed cross-correlations is achieved using a simple range-dependent model, constrained by earlier, active tomographic studies in the area. In particular, the model correctly predicts the existence of two weakly dispersive normal modes in the microseism frequency range, with the group speed of one of the normal modes being smaller than the sound speed in water. The agreement justifies our interpretation of the peaks of the measured cross-correlation function of ambient noise as modal arrivals, with dispersion that is sensitive to crustal velocity structure. Our observations are consistent with Scholte to Moho head wave coupled propagation, with double mode conversion occurring due to the bathymetric variations between receivers. We thus demonstrate the feasibility of interrogating crustal properties using noise interferometry of moored hydrophone data at ranges in excess of 120 km.

Description: Recent tectonic reconstructions of the South Atlantic have partitioned the ocean basin into several segments based upon one or more proposed intraplate South American deformation zones. In several of these reconstructions, opening of the southern segment(s) by seafloor spreading prior to Aptian-Albian time is accompanied by contemporaneous strike-slip motion along an intraplate boundary extending southeastward from the Andean Cochabamba—Santa Cruz bend to the Rio Grande Fracture Zone (RGFZ). We have examined new magnetic data over the Pelotas, Santos and Campos Basins, offshore Argentina and Brazil, acquired by ION-GXT in tandem with long-offset, long record seismic reflection data, and identified seafloor spreading anomalies M4, M3, M2 and M0 (~131, ~129, ~128 and ~125 Ma). Integrating these results with our earlier work, we have been able to correlate magnetochrons M4, M3, M2 and M0 north and south of the RGFZ on the South American margin, and north and south of the Walvis Ridge on the African side. Our results are therefore inconsistent with diachronous opening models that involve substantial continental strike-slip motion north of RGFZ during M4 to M0 time. Although the ocean basin may have opened from south to north, our results indicate that seafloor spreading began north of the RGFZ earlier than previously proposed.

Description: Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments.

Description: The ability to integrate ‘omics’ (i.e. transcriptomics and proteomics) is becoming increasingly important to the understanding of regulatory mechanisms. There are currently no tools available to identify differentially expressed genes (DEGs) across different ‘omics’ data types or multi-dimensional data including time courses. We present fCI (f-divergence Cut-out Index), a model capable of simultaneously identifying DEGs from continuous and discrete transcriptomic, proteomic and integrated proteogenomic data. We show that fCI can be used across multiple diverse sets of data and can unambiguously find genes that show functional modulation, developmental changes or misregulation. Applying fCI to several proteogenomics datasets, we identified a number of important genes that showed distinctive regulation patterns. The package fCI is available at R Bioconductor and http://software.steenlab.org/fCI/ .

Description: Next generation sequencing of cellular RNA is making it possible to characterize genes and alternative splicing in unprecedented detail. However, designing bioinformatics tools to accurately capture splicing variation has proven difficult. Current programs can find major isoforms of a gene but miss lower abundance variants, or are sensitive but imprecise. CLASS2 is a novel open source tool for accurate genome-guided transcriptome assembly from RNA-seq reads based on the model of splice graph. An extension of our program CLASS, CLASS2 jointly optimizes read patterns and the number of supporting reads to score and prioritize transcripts, implemented in a novel, scalable and efficient dynamic programming algorithm. When compared against reference programs, CLASS2 had the best overall accuracy and could detect up to twice as many splicing events with precision similar to the best reference program. Notably, it was the only tool to produce consistently reliable transcript models for a wide range of applications and sequencing strategies, including ribosomal RNA-depleted samples. Lightweight and multi-threaded, CLASS2 requires 〈3GB RAM and can analyze a 350 million read set within hours, and can be widely applied to transcriptomics studies ranging from clinical RNA sequencing, to alternative splicing analyses, and to the annotation of new genomes.

Description: A method to estimate the rotation change in the orientation of the centre-of-figure (CF) frame caused by earthquakes is proposed for the first time. This method involves using the point dislocation theory based on a spherical, non-rotating, perfectly elastic and isotropic (SNREI) Earth. The rotation change in the orientation is related solely to the toroidal displacements of degree one induced by the vertical dip slip dislocation, and the spheroidal displacements induced by an earthquake have no contribution. The effects of two recent large earthquakes, the 2004 Sumatra and the 2011 Tohoku-Oki, are studied. Results showed that the Sumatra and Tohoku-Oki earthquakes both caused the CF frame to rotate by at least tens of μas (micro-arc-second). Although the visible co-seismic displacements are identified and removed from the coordinate time-series, the rotation change due to the unidentified ones and errors in removal is non-negligible. Therefore, the rotation change in the orientation of the CF frame due to seismic deformation should be taken into account in the future in reference frame and geodesy applications.

Description: Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of ‘actionable’ mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing. We developed FACETS, an ASCN tool and open-source software with a broad application to whole genome, whole-exome, as well as targeted panel sequencing platforms. It is a fully integrated stand-alone pipeline that includes sequencing BAM file post-processing, joint segmentation of total- and allele-specific read counts, and integer copy number calls corrected for tumor purity, ploidy and clonal heterogeneity, with comprehensive output and integrated visualization. We demonstrate the application of FACETS using The Cancer Genome Atlas (TCGA) whole-exome sequencing of lung adenocarcinoma samples. We also demonstrate its application to a clinical sequencing platform based on a targeted gene panel.

Description: We present SWAN, a statistical framework for robust detection of genomic structural variants in next-generation sequencing data and an analysis of mid-range size insertion and deletions (〈10 Kb) for whole genome analysis and DNA mixtures. To identify these mid-range size events, SWAN collectively uses information from read-pair, read-depth and one end mapped reads through statistical likelihoods based on Poisson field models. SWAN also uses soft-clip/split read remapping to supplement the likelihood analysis and determine variant boundaries. The accuracy of SWAN is demonstrated by in silico spike-ins and by identification of known variants in the NA12878 genome. We used SWAN to identify a series of novel set of mid-range insertion/deletion detection that were confirmed by targeted deep re-sequencing. An R package implementation of SWAN is open source and freely available.

Description: High-throughput screening (HTS) is an indispensable tool for drug (target) discovery that currently lacks user-friendly software tools for the robust identification of putative hits from HTS experiments and for the interpretation of these findings in the context of systems biology. We developed HiTSeekR as a one-stop solution for chemical compound screens, siRNA knock-down and CRISPR/Cas9 knock-out screens, as well as microRNA inhibitor and -mimics screens. We chose three use cases that demonstrate the potential of HiTSeekR to fully exploit HTS screening data in quite heterogeneous contexts to generate novel hypotheses for follow-up experiments: (i) a genome-wide RNAi screen to uncover modulators of TNFα, (ii) a combined siRNA and miRNA mimics screen on vorinostat resistance and (iii) a small compound screen on KRAS synthetic lethality. HiTSeekR is publicly available at http://hitseekr.compbio.sdu.dk . It is the first approach to close the gap between raw data processing, network enrichment and wet lab target generation for various HTS screen types.

Description: Determining thin layer thickness is very important for reservoir characterization and CO 2 quantification. Given its high time–frequency resolution and robustness, the complex spectral decomposition method was applied on time-lapse 3-D seismic data from the Ketzin pilot site for CO 2 storage to evaluate the frequency-dependent characteristics of thin layers at the injection level. Higher temporal resolution and more stratigraphic details are seen in the all-frequency and monochromatic reflectivity amplitude sections obtained by complex spectral decomposition compared to the stacked sections. The mapped geologic discontinuities within the reservoir are consistent with the preferred orientation of CO 2 propagation. Tuning frequency mapping shows the thicknesses of the reservoir sandstone and gaseous CO 2 is consistent with the measured thickness of the sandstone unit from well logging. An attempt to discriminate between pressure effects and CO 2 saturation using the extracted tuning frequency indicates that CO 2 saturation is the main contributor to the amplitude anomaly at the Ketzin site. On the basis of determined thickness of gaseous CO 2 in the reservoir, quantitative analysis of the amount of CO 2 was performed and shows a discrepancy between the injected and calculated CO 2 mass. This may be explained by several uncertainties, like structural reservoir heterogeneity, a limited understanding of the complex subsurface conditions, error of determined tuning frequency, the presence of ambient noise and ongoing CO 2 dissolution.

Description: In this study, we propose an approach for determining the geopotential difference using high-frequency-stability microwave links between satellite and ground station based on Doppler cancellation system. Suppose a satellite and a ground station are equipped with precise optical-atomic clocks (OACs) and oscillators. The ground oscillator emits a signal with frequency f a towards the satellite and the satellite receiver (connected with the satellite oscillator) receives this signal with frequency f b which contains the gravitational frequency shift effect and other signals and noises. After receiving this signal, the satellite oscillator transmits and emits, respectively, two signals with frequencies f b and f c towards the ground station. Via Doppler cancellation technique, the geopotential difference between the satellite and the ground station can be determined based on gravitational frequency shift equation by a combination of these three frequencies. For arbitrary two stations on ground, based on similar procedures as described above, we may determine the geopotential difference between these two stations via a satellite. Our analysis shows that the accuracy can reach 1 m 2 s – 2 based on the clocks’ inaccuracy of about 10 –17 (s s –1 ) level. Since OACs with instability around 10 –18 in several hours and inaccuracy around 10 –18 level have been generated in laboratory, the proposed approach may have prospective applications in geoscience, and especially, based on this approach a unified world height system could be realized with one-centimetre level accuracy in the near future.

Description: Comprehensive analytical solutions to 3-D axisymmetric problems for static response of multilayered thermoelastic media subjected to surface loads and containing sources are presented in this study. The solution strategy employs Laplace and Hankel transforms to the field variables. The problem is formulated in cylindrical coordinate system and in this coordinate system vector surface harmonics and generalized propagator matrix are introduced to find the solution for the problem for the behaviour of thermoelastic multilayered media subject to surface loads and containing heat sources. A high-order adaptive Gaussian quadrature method with continued fraction expansions is employed to approximate the integral solutions expressed in terms of semi-infinite Hankel-type integrals. It is the first time to apply the proposed solution method to investigate the behaviour of repository for heat-emitting high-level nuclear waste (HLW) in a geological formation where the HLW can be regarded as a decaying with time point heat source.

Description: We present a series of processes for understanding and analysing controlled-source electromagnetic (CSEM) responses for a conductive and permeable earth. To realize the CSEM response, a new 3-D CSEM forward modelling algorithm based on an edge finite element method for both electrically conductive and magnetically permeable heterogeneities is developed. The algorithm shows highly accurate results in validation tests against a semi-analytic solution for stratified earth and an integral form of the scattered field. We describe the vector behaviour of an anomalous magnetic field originating from a conductive and permeable anomaly when the loop sources are deployed over a conductive half-space. The CSEM response of the conductive and permeable anomaly is classified into three effects originating from: conductivity perturbations, permeability perturbations and the coupling of these two effects. The separated individual results and the corresponding integral equation form of the anomalous field help to better understand the physical behaviour. We confirm the characteristic features of the CSEM response from the conductive and permeable anomaly, for example, (1) the general dominance of the induction effect in the out-of-phase response accompanied by a non-negligible magnetization effect from the magnetic anomaly in a conductive half-space and (2) the dominance of near frequency-independent magnetization effects in the in-phase response at relatively low frequencies and change in ruling part of the in-phase response into the induction effect as the frequency increases. We also demonstrate the effect of coupling mode and show that its maximum contribution is limited to a few per cent level of other two modes, induction and magnetization mode, even when the heterogeneity of our model is strong. In our synthetic survey, using examples of land-based profiling surveys of low induction number and intermediate regime, we find that the effect of magnetization can be used as an indicator of the existence of magnetic material. One important point to note from this study is the importance of accurate cancelling-out or estimation of free-space responses, which can mask the magnetic responses to imaging the varying magnetic property.

Description: Disease-gene identification is a challenging process that has multiple applications within functional genomics and personalized medicine. Typically, this process involves both finding genes known to be associated with the disease (through literature search) and carrying out preliminary experiments or screens (e.g. linkage or association studies, copy number analyses, expression profiling) to determine a set of promising candidates for experimental validation. This requires extensive time and monetary resources. We describe Beegle , an online search and discovery engine that attempts to simplify this process by automating the typical approaches. It starts by mining the literature to quickly extract a set of genes known to be linked with a given query, then it integrates the learning methodology of Endeavour (a gene prioritization tool) to train a genomic model and rank a set of candidate genes to generate novel hypotheses. In a realistic evaluation setup, Beegle has an average recall of 84% in the top 100 returned genes as a search engine, which improves the discovery engine by 12.6% in the top 5% prioritized genes. Beegle is publicly available at http://beegle.esat.kuleuven.be/ .

Description: Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non-trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large-scale data sets.

Description: Extraction of fluids from subsurface reservoirs induces changes in pore pressure, leading not only to geomechanical changes, but also perturbations in seismic velocities and hence observable seismic attributes. Time-lapse seismic analysis can be used to estimate changes in subsurface hydromechanical properties and thus act as a monitoring tool for geological reservoirs. The ability to observe and quantify changes in fluid, stress and strain using seismic techniques has important implications for monitoring risk not only for petroleum applications but also for geological storage of CO 2 and nuclear waste scenarios. In this paper, we integrate hydromechanical simulation results with rock physics models and full-waveform seismic modelling to assess time-lapse seismic attribute resolution for dynamic reservoir characterization and hydromechanical model calibration. The time-lapse seismic simulations use a dynamic elastic reservoir model based on a North Sea deep reservoir undergoing large pressure changes. The time-lapse seismic traveltime shifts and time strains calculated from the modelled and processed synthetic data sets (i.e. pre-stack and post-stack data) are in a reasonable agreement with the true earth models, indicating the feasibility of using 1-D strain rock physics transform and time-lapse seismic processing methodology. Estimated vertical traveltime shifts for the overburden and the majority of the reservoir are within ±1 ms of the true earth model values, indicating that the time-lapse technique is sufficiently accurate for predicting overburden velocity changes and hence geomechanical effects. Characterization of deeper structure below the overburden becomes less accurate, where more advanced time-lapse seismic processing and migration is needed to handle the complex geometry and strong lateral induced velocity changes. Nevertheless, both migrated full-offset pre-stack and near-offset post-stack data image the general features of both the overburden and reservoir units. More importantly, the results from this study indicate that integrated seismic and hydromechanical modelling can help constrain time-lapse uncertainty and hence reduce risk due to fluid extraction and injection.

Description: A new plate motions model for the northwest Africa–North America Plate pair during the Oligocene and early Miocene is presented. The model is accompanied by a high-resolution isochron map for the central Atlantic region, resulting from a re-examination of 423 ship tracks from the NGDC data base for the area between the 15°20' FZ and the Azores triple junction. A new digital model of fracture zones for this region and a set of 309 magnetic profiles crossing the Oligocene to recent oceanic crust within the study area allowed to determine accurate finite reconstruction poles for the North America–northwest Africa conjugate plate pair between the early Miocene (Chron 6) and the early Oligocene (Chron 13). For times older than Chron 7 (~25 Ma), the finite reconstruction poles were calculated using a reliable data set coming exclusively from the region south of the Canary Islands FZ (~32°N), which allowed to test the rigidity of the northwest African oceanic lithosphere during the Oligocene–early Miocene phase of Atlas orogeny. A comparison of theoretical magnetic isochrons with observed magnetic lineations systematically shows that anomalously high spreading rates occurred in the area north of the Canary Islands FZ before Chron 7, thereby suggesting that the formation of the Atlas mountain, rather than being a localized intracontinental process, was logically linked to the central Atlantic spreading history. Thus, an independent Moroccan Plate could have existed during the Oligocene–early Miocene time interval, which included both the oceanic lithosphere north of the Canary Islands FZ and the northern Maghrebian areas of Morocco, Algeria and Tunisia. In this eventuality, the Atlas mountain belt should be reinterpreted as a giant flower structure associated with dextral transpression.

Description: Spectral induced polarization measurements are affected by temperature variations due to a variety of temperature-dependent parameters that control the complex electrical conductivity. Most important is the influence of the ion mobility, which increases with increasing temperature. It is responsible for the increase of the conductivity of the fluid in the pores with temperature and influences the electrical double layer on the mineral surface. This work is based on laboratory measurements of 13 sandstone samples from different sources with different geological and petrophysical characteristics. We measured the complex impedance in a frequency range from 0.01 to 100 Hz and a temperature range from 0 to 40 °C. The main observation is a decrease of the characteristic time (defined by the inverse of the frequency, at which the phase shift is maximum) with increasing temperature. The strength of this decrease differs from one sample to another. The temperature dependence of the phase shift magnitude cannot easily be generalized, as it depends on the particular sample. The experimental findings suggest that neglecting the influence of temperature on complex conductivity may lead to significant errors when estimating hydraulic conductivity from relaxation time. We also simulate the temperature dependence with a theoretical model of membrane polarization and review some of the model properties, with an emphasis on the temperature dependence of the parameters. The model reproduces several features characterizing the measured data, including the temperature dependence of the characteristic times. Computed tomography and microscope images of the pore structure of three samples also allow us to associate differences in the geometrical parameters used in the modelling with pore scale parameters of the actual samples.

Description: A sequence of large earthquakes occurred along the North Anatolian fault in the 20th century. These earthquakes, including the 1999 Izmit/Düzce earthquakes, generally propagated westward towards the Marmara Sea, defining the Main Marmara fault as a potential seismic gap. It is important to conduct a detailed assessment of the seismic hazards along the main Marmara fault because the megacity Istanbul lies only approximately 10 km north of the eastern segment of the Main Marmara fault, which is referred to as the Princes’ Islands Fault segment (PIF). Here, we study the locking status of this fault segment to evaluate the seismic hazard potential. For the first time, combined ascending and descending Interferometric Synthetic Aperture Radar and Global Positioning System observations were used to investigate the crustal deformation associated with the PIF. After careful corrections of the estimated ground velocity, a deformation pattern relating to fault locking near the Princes’ Islands was identified. The modeling results revealed that the slip rate and locking depth of the fault segment show a clear trade-off, which were estimated as 18.9 ± 7.2 mm yr –1 and 12.1 ± 7.0 km, respectively. With a moment accumulation rate of 1.7 ± 0.4  x  10 17 Nm yr –1 (proportional to the product of slip rate and locking depth), our results imply a build-up of a geodetic moment on the PIF and therefore a potential for earthquake hazards in the vicinity of the Istanbul megacity.

Description: Knowledge about the pressure dependency of elastic and electrical properties is important for a variety of geophysical applications. We present a technique to invert for the stiff and compliant porosity from velocity measurements made as a function of differential pressure on saturated sandstones. A dual porosity concept is used for dry rock compressibility and a squirt model is employed for the pressure and frequency dependent elastic properties of the rocks when saturated. The total porosity obtained from inversion shows satisfactory agreement with experimental results. The electrical cementation factor was determined using the inverted porosity in combination with measured electrical conductivity. It was found that cementation factor increased exponentially with increasing differential pressure during isostatic loading. Elastic compressibility, electrical cementation factor and electrical conductivity of the saturated rocks correlate linearly with compliant porosity, and electrical cementation factor and electrical conductivity exhibit linear correlations with elastic compressibility of the saturated rocks under loading. The results show that the dual porosity concept is sufficient to explain the pressure dependency of elastic, electrical and joint elastic-electrical properties of saturated porous sandstones.

Description: A new plate motions model for the northwest Africa–North America Plate pair during the Oligocene and early Miocene is presented. The model is accompanied by a high-resolution isochron map for the central Atlantic region, resulting from a re-examination of 423 ship tracks from the NGDC data base for the area between the 15°20' FZ and the Azores triple junction. A new digital model of fracture zones for this region and a set of 309 magnetic profiles crossing the Oligocene to recent oceanic crust within the study area allowed to determine accurate finite reconstruction poles for the North America–northwest Africa conjugate plate pair between the early Miocene (Chron 6) and the early Oligocene (Chron 13). For times older than Chron 7 (~25 Ma), the finite reconstruction poles were calculated using a reliable data set coming exclusively from the region south of the Canary Islands FZ (~32°N), which allowed to test the rigidity of the northwest African oceanic lithosphere during the Oligocene–early Miocene phase of Atlas orogeny. A comparison of theoretical magnetic isochrons with observed magnetic lineations systematically shows that anomalously high spreading rates occurred in the area north of the Canary Islands FZ before Chron 7, thereby suggesting that the formation of the Atlas mountain, rather than being a localized intracontinental process, was logically linked to the central Atlantic spreading history. Thus, an independent Moroccan Plate could have existed during the Oligocene–early Miocene time interval, which included both the oceanic lithosphere north of the Canary Islands FZ and the northern Maghrebian areas of Morocco, Algeria and Tunisia. In this eventuality, the Atlas mountain belt should be reinterpreted as a giant flower structure associated with dextral transpression.

Description: Tumors are characterized by properties of genetic instability, heterogeneity, and significant oligoclonality. Elucidating this intratumoral heterogeneity is challenging but important. In this study, we propose a framework, BubbleTree, to characterize the tumor clonality using next generation sequencing (NGS) data. BubbleTree simultaneously elucidates the complexity of a tumor biopsy, estimating cancerous cell purity, tumor ploidy, allele-specific copy number, and clonality and represents this in an intuitive graph. We further developed a three-step heuristic method to automate the interpretation of the BubbleTree graph, using a divide-and-conquer strategy. In this study, we demonstrated the performance of BubbleTree with comparisons to similar commonly used tools such as THetA2, ABSOLUTE, AbsCN-seq and ASCAT, using both simulated and patient-derived data. BubbleTree outperformed these tools, particularly in identifying tumor subclonal populations and polyploidy. We further demonstrated BubbleTree's utility in tracking clonality changes from patients’ primary to metastatic tumor and dating somatic single nucleotide and copy number variants along the tumor clonal evolution. Overall, the BubbleTree graph and corresponding model is a powerful approach to provide a comprehensive spectrum of the heterogeneous tumor karyotype in human tumors. BubbleTree is R-based and freely available to the research community ( https://www.bioconductor.org/packages/release/bioc/html/BubbleTree.html ).

Description: We present a distributed slip model for the 1999 M w 6.3 Chamoli earthquake of north India using interferometric synthetic aperture radar (InSAR) data from both ascending and descending orbits and Bayesian estimation of confidence levels and trade-offs of the model geometry parameters. The results of fault-slip inversion in an elastic half-space show that the earthquake ruptured a $9 _{ - 2.2}^{\circ + 3.4}$ northeast-dipping plane with a maximum slip of ~1 m. The fault plane is located at a depth of ~ $15.9_{ - 3.0}^{ + 1.1}$ km and is ~120 km north of the Main Frontal Thrust, implying that the rupture plane was on the northernmost detachment near the mid-crustal ramp of the Main Himalayan Thrust. The InSAR-determined moment is 3.35 x 10 18 Nm with a shear modulus of 30 GPa, equivalent to M w 6.3, which is smaller than the seismic moment estimates of M w 6.4–6.6. Possible reasons for this discrepancy include the trade-off between moment and depth, uncertainties in seismic moment tensor components for shallow dip-slip earthquakes and the role of earth structure models in the inversions. The released seismic energy from recent earthquakes in the Garhwal region is far less than the accumulated strain energy since the 1803 M s 7.5 earthquake, implying substantial hazard of future great earthquakes.

Description: Maximizing vertical resolution is a key objective in seismic data processing. Early deconvolution and spectral balancing algorithms assumed that the seismic source wavelet was temporally invariant, or stationary. In practice, seismic scattering and attenuation give rise to non-stationary seismic source wavelets. To address this issue, most conventional time-varying deconvolution wavelet shaping and spectral modelling techniques using the stationary polynomial fitting assume the wavelet to be locally stationary within a small number of overlapping analysis windows while the fitting coefficients are invariant with all the frequencies. In this paper, we show an improvement obtained by modelling smoothly varying spectra of the seismic wavelet using non-stationary polynomial fitting in the time–frequency domain. We first decompose each seismic trace using a generalized S-transform that provides a good time–frequency distribution for the estimation of the time-varying wavelet spectra. We then model the slowly varying source wavelet spectrum at each time sample by a smooth low-order polynomial. Finally, we spectrally balance the modelled wavelet to flatten the seismic response, thereby increasing vertical resolution. We calibrate the algorithm on a simple synthetic and then apply it to a 3-D land survey acquired in western China, showing the value on both vertical slices through seismic amplitude and attribute time slices. Our new algorithm significantly improves the vertical resolution of the seismic signal, while not increasing the noise.

Description: Knowledge about the pressure dependency of elastic and electrical properties is important for a variety of geophysical applications. We present a technique to invert for the stiff and compliant porosity from velocity measurements made as a function of differential pressure on saturated sandstones. A dual porosity concept is used for dry rock compressibility and a squirt model is employed for the pressure and frequency dependent elastic properties of the rocks when saturated. The total porosity obtained from inversion shows satisfactory agreement with experimental results. The electrical cementation factor was determined using the inverted porosity in combination with measured electrical conductivity. It was found that cementation factor increased exponentially with increasing differential pressure during isostatic loading. Elastic compressibility, electrical cementation factor and electrical conductivity of the saturated rocks correlate linearly with compliant porosity, and electrical cementation factor and electrical conductivity exhibit linear correlations with elastic compressibility of the saturated rocks under loading. The results show that the dual porosity concept is sufficient to explain the pressure dependency of elastic, electrical and joint elastic-electrical properties of saturated porous sandstones.

Description: We use a Bayesian formalism combined with a grid node discretization for the linear inversion of gravimetric data in terms of 3-D density distribution. The forward modelling and the inversion method are derived from seismological inversion techniques in order to facilitate joint inversion or interpretation of density and seismic velocity models. The Bayesian formulation introduces covariance matrices on model parameters to regularize the ill-posed problem and reduce the non-uniqueness of the solution. This formalism favours smooth solutions and allows us to specify a spatial correlation length and to perform inversions at multiple scales. We also extract resolution parameters from the resolution matrix to discuss how well our density models are resolved. This method is applied to the inversion of data from the volcanic island of Basse-Terre in Guadeloupe, Lesser Antilles. A series of synthetic tests are performed to investigate advantages and limitations of the methodology in this context. This study results in the first 3-D density models of the island of Basse-Terre for which we identify: (i) a southward decrease of densities parallel to the migration of volcanic activity within the island, (ii) three dense anomalies beneath Petite Plaine Valley, Beaugendre Valley and the Grande-Découverte-Carmichaël-Soufrière Complex that may reflect the trace of former major volcanic feeding systems, (iii) shallow low-density anomalies in the southern part of Basse-Terre, especially around La Soufrière active volcano, Piton de Bouillante edifice and along the western coast, reflecting the presence of hydrothermal systems and fractured and altered rocks.

Description: In order to perform gas exploration and determine the distribution pattern of gas in the Yanchang Oil Field in the eastern part of the North Shaanxi Slope, Ordos Basin, China, gravity and magnetic survey data were systemically collated, processed and interpreted in combination with the drilling data and recent seismic data. The genesis of gravity and magnetic anomalies and the relationship between the characteristics of the gravity and magnetic fields and known gas distribution were explored in order to predict the favourable exploration targets for gas. Gravity anomalies resulted both from the lateral variation in density of the basement rock and lateral lithologic transformation in the sedimentary cover. The regional magnetic anomalies were mainly caused by the basement metamorphic rocks and the residual magnetic anomalies may reflect the amount and general location of the volcanic materials in the overlying strata. The residual gravity and magnetic anomalies generated by high-density sandstone and high content of volcanics in the gas reservoir of the upper Paleozoic distorted and deformed the anomaly curves when they were stacked onto the primary background anomaly. The gas wells were generally found to be located in the anomaly gradient zones, or the distorted part of contour lines, and the flanks of high and low anomalies, or the transitional zones between anomaly highs and lows. The characteristics of gravity and magnetic fields provide significant information that can be used for guidance when exploring the distribution of gas. Based on these characteristics, five favourable areas for gas exploration were identified; these are quasi-equally spaced like a strip extending from the southeast to the northwest.

Description: We compute the gravimetric factor at the Chandler wobble (CW) frequency using time-series from superconducting gravimeters (SG) longer than a decade. We first individually process the polar motion and data at each individual gravity station to estimate the gravimetric factor amplitude and phase, then we make a global analysis by applying a stacking method to different subsets of up to seven SG stations. The stacking is an efficient way of getting rid of local effects and improving the signal-to-noise ratio of the combined data sets. Using the stacking method, we find a gravimetric factor amplitude and phase of 1.118 ± 0.016 and –0.45 ± 0.66 deg, respectively, which is smaller in amplitude than expected. The sources of error are then carefully considered. For both local and global analyses, the uncertainties on our results are reliably constrained by computing the standard deviation of the estimates of the gravimetric factor amplitude and phase for increasing length of the time-series. Constraints on the CW anelastic dissipation can be set since any departure of the gravimetric factor from its elastic value may provide some insights into the dissipative processes that occur at the CW period. In particular, assuming given rheological models for the Earth's mantle enables us to make the link between the gravimetric factor phase and the CW quality factor.

Description: Spectral induced polarization measurements are affected by temperature variations due to a variety of temperature-dependent parameters that control the complex electrical conductivity. Most important is the influence of the ion mobility, which increases with increasing temperature. It is responsible for the increase of the conductivity of the fluid in the pores with temperature and influences the electrical double layer on the mineral surface. This work is based on laboratory measurements of 13 sandstone samples from different sources with different geological and petrophysical characteristics. We measured the complex impedance in a frequency range from 0.01 to 100 Hz and a temperature range from 0 to 40 °C. The main observation is a decrease of the characteristic time (defined by the inverse of the frequency, at which the phase shift is maximum) with increasing temperature. The strength of this decrease differs from one sample to another. The temperature dependence of the phase shift magnitude cannot easily be generalized, as it depends on the particular sample. The experimental findings suggest that neglecting the influence of temperature on complex conductivity may lead to significant errors when estimating hydraulic conductivity from relaxation time. We also simulate the temperature dependence with a theoretical model of membrane polarization and review some of the model properties, with an emphasis on the temperature dependence of the parameters. The model reproduces several features characterizing the measured data, including the temperature dependence of the characteristic times. Computed tomography and microscope images of the pore structure of three samples also allow us to associate differences in the geometrical parameters used in the modelling with pore scale parameters of the actual samples.

Description: The streaming potential phenomenon is produced by the flow of an electrolyte in a porous medium and is used for geophysical prospecting. It is quantified through an electrokinetic (EK) coefficient. The dependence of the EK coefficient on the conductivity of the electrolyte is described by the Helmholtz–Smoluchowski (HS) equation. This equation provides successful forecasts of the EK coefficient in the standard range of concentration. However, experimental measurements show deviations to this equation at extreme low and extreme high salinities. The aim of this study is to model the EK coefficient using Lattice Boltzmann simulations in a 2-D capillary channel, with a view to understanding these deviations. The effect of the constitutive parameters of the HS equation such as the permittivity and the viscosity is discussed. The validity of the HS equation using strong potentials is assessed. Finally, a model of bulk fluid conductivity is derived. This model allows to take into account the change of local ionic distribution in the vicinity of the mineral. It appears to have a significant impact on the derivation of potentials at low salinities and in the presence of polyvalent counterions.

Description: Analysing independent 1-yr data sets of 10 European superconducting gravimeters (SG) reveals statistically significant temporal variations of M2 tidal parameters. Both common short-term (〈2 yr) and long-term (〉2 yr) features are identified in all SG time-series but one. The averaged variations of the amplitude factor are about 0.2. The path of load vector variations equivalent to the temporal changes of tidal parameters suggests the presence of an 8.85 yr modulation (lunar perigee). The tidal waves having the potential to modulate M2 with this period belong to the 3rd degree constituents. Their amplitude factors turn out to be much closer to body tide model predictions than that of the main 2nd degree M2, which indicates ocean loading for 3rd degree waves to be less prominent than for 2nd degree waves within the M2 group. These two different responses to the loading suggest that the observed modulation is more due to insufficient frequency resolution of limited time-series rather than to time variable loading. Presently, SG gravity time-series are still too short to prove if time variable loading processes are involved too as in case of the annual M2 modulation known to appear for analysis intervals of less than 1 yr. Whatever the variations are caused by, they provide the upper accuracy limit for earth model validation and permit estimating the temporal stability of SG scale factors and assessing the quality of gravity time-series.

Description: Extraction of fluids from subsurface reservoirs induces changes in pore pressure, leading not only to geomechanical changes, but also perturbations in seismic velocities and hence observable seismic attributes. Time-lapse seismic analysis can be used to estimate changes in subsurface hydromechanical properties and thus act as a monitoring tool for geological reservoirs. The ability to observe and quantify changes in fluid, stress and strain using seismic techniques has important implications for monitoring risk not only for petroleum applications but also for geological storage of CO 2 and nuclear waste scenarios. In this paper, we integrate hydromechanical simulation results with rock physics models and full-waveform seismic modelling to assess time-lapse seismic attribute resolution for dynamic reservoir characterization and hydromechanical model calibration. The time-lapse seismic simulations use a dynamic elastic reservoir model based on a North Sea deep reservoir undergoing large pressure changes. The time-lapse seismic traveltime shifts and time strains calculated from the modelled and processed synthetic data sets (i.e. pre-stack and post-stack data) are in a reasonable agreement with the true earth models, indicating the feasibility of using 1-D strain rock physics transform and time-lapse seismic processing methodology. Estimated vertical traveltime shifts for the overburden and the majority of the reservoir are within ±1 ms of the true earth model values, indicating that the time-lapse technique is sufficiently accurate for predicting overburden velocity changes and hence geomechanical effects. Characterization of deeper structure below the overburden becomes less accurate, where more advanced time-lapse seismic processing and migration is needed to handle the complex geometry and strong lateral induced velocity changes. Nevertheless, both migrated full-offset pre-stack and near-offset post-stack data image the general features of both the overburden and reservoir units. More importantly, the results from this study indicate that integrated seismic and hydromechanical modelling can help constrain time-lapse uncertainty and hence reduce risk due to fluid extraction and injection.

Description: A sequence of large earthquakes occurred along the North Anatolian fault in the 20th century. These earthquakes, including the 1999 Izmit/Düzce earthquakes, generally propagated westward towards the Marmara Sea, defining the Main Marmara fault as a potential seismic gap. It is important to conduct a detailed assessment of the seismic hazards along the main Marmara fault because the megacity Istanbul lies only approximately 10 km north of the eastern segment of the Main Marmara fault, which is referred to as the Princes’ Islands Fault segment (PIF). Here, we study the locking status of this fault segment to evaluate the seismic hazard potential. For the first time, combined ascending and descending Interferometric Synthetic Aperture Radar and Global Positioning System observations were used to investigate the crustal deformation associated with the PIF. After careful corrections of the estimated ground velocity, a deformation pattern relating to fault locking near the Princes’ Islands was identified. The modeling results revealed that the slip rate and locking depth of the fault segment show a clear trade-off, which were estimated as 18.9 ± 7.2 mm yr –1 and 12.1 ± 7.0 km, respectively. With a moment accumulation rate of 1.7 ± 0.4  x  10 17 Nm yr –1 (proportional to the product of slip rate and locking depth), our results imply a build-up of a geodetic moment on the PIF and therefore a potential for earthquake hazards in the vicinity of the Istanbul megacity.

Description: Deformation analysis in general and strain analysis in particular using permanent GPS networks require proper analysis of time-series in which all functional effects are taken into consideration and all stochastic effects are captured using an appropriate noise model. This contribution addresses both issues when considering the strain parameters of a GPS network. Estimates of spatial correlation, time correlated noise, and multivariate power spectrum for daily position time-series of the Southern California Integrated GPS Network (SCIGN) stations collected between 1996 and 2011 are obtained. Significant signals with periods of 13.63 d and those related to the GPS draconitic year are identified in these time-series. We aim to assess the effect of a realistic noise model of the series on the uncertainties of the strain parameters including displacements, normal and shear strains, and rotations. For the SCIGN network considered, the following results are highlighted. Contrary to the common belief, the uncertainties of the displacements parameters become smaller when taking a realistic noise model into account. This however was not the case when assessing the noise characteristics of the normal and shear strain, and rotation parameters. The uncertainties increase nearly by a factor of two, in agreement to what is expected. Some of the significant deformation parameters of the white noise model become less significant in case of the realistic noise model.

Description: We have extended backwards from 2001 to 1979 the current release 05 (RL05) of the Gravity Recovery and Climate Experiment (GRACE) Atmospheric and Oceanic De-aliasing Level-1B (AOD1B) product and studied the impact of this and a previous release 04 (RL04) of the AOD1B product on precise orbits of five altimetry satellites (ERS-1, ERS-2, TOPEX/Poseidon, Envisat and Jason-1) for the time span 1991–2012, as compared to the case when no AOD1B product is used. We have found that using AOD1B RL05 product reduces root mean square (RMS) fits of satellite laser ranging (SLR) observations by about 1.0–6.4 per cent, 2-d arc overlaps in radial, cross-track and along-track directions by about 1.3–12.0, 0.3–10.0 and 2.0–10.0 per cent, respectively, for various satellites tested, as compared to the case without AOD1B product. Using AOD1B RL05 product instead of RL04 one reduces SLR RMS fits by 0.1–0.7 per cent, 2-d arc overlaps in radial, cross-track and along-track directions by 0.1–0.6, 0.1–1.3 and 0.2–1.2 per cent, respectively, for the satellite orbits tested. The multi-mission crossover analysis shows that the application of an AOD1B product reduces the scatter of radial errors by 0.4–2.8 per cent for the satellite missions studied. At the regions with the most pronounced changes the use of the AOD1B products improves the consistency between the sea level as measured by the TOPEX and ERS-2 missions and by the Jason-1 and Envisat missions by 5 to 10 per cent (globally by about 2 per cent). The results of our study show that extended AOD1B RL05 product performs better than the AOD1B RL04 and improves orbits of altimetry satellites and consistency of sea level products.

Description: A new analytical method for the computation of a truncated series of solid spherical harmonic coefficients (HCs) from data on a spheroid (i.e. an oblate ellipsoid of revolution) is derived, using a transformation between surface and solid spherical HCs. A two-step procedure is derived to extend this transformation beyond degree and order (d/o) 520. The method is compared to the Hotine–Jekeli transformation in a numerical study based on the EGM2008 global gravity model. Both methods are shown to achieve submicrometre precision in terms of height anomalies for a model to d/o 2239. However, both methods result in spherical harmonic models that are different by up to 7.6 mm in height anomalies and 2.5 mGal in gravity disturbances due to the different coordinate system used. While the Hotine–Jekeli transformation requires the use of an ellipsoidal coordinate system, the new method uses only spherical polar coordinates. The Hotine–Jekeli transformation is numerically more efficient, but the new method can more easily be extended to cases where (a linear combination of) normal derivatives of the function under consideration are given on the surface of the spheroid. It therefore provides a solution to many types of ellipsoidal boundary-value problems in the spectral domain.

Description: We study the accuracy and numerical stability of three eigenvector sets for modelling the coupled poroelastic and electromagnetic layered-Earth response. We use a known eigenvector set, its flux-normalized version and a newly derived flux-normalized set. The new set is chosen such that the system is properly uncoupled when the coupling between the poroelastic and electromagnetic fields vanishes. We carry out two different numerical stability tests: the first test focuses on the internal system, eigenvector and eigenvalue consistency; the second test investigates the stability and preciseness of the flux-normalized systems by looking at identity relations. We find that the known set shows the largest deviation for both tests, whereas the new set performs best. In two additional numerical modelling experiments, these numerical inaccuracies are shown to generate numerical noise levels comparable to small signals, such as signals coming from the important interface conversion responses, especially when the coupling coefficient is small. When coupling vanishes completely, the known set does not produce proper results. The new set produces numerically stable and accurate results in all situations. We therefore strongly recommend to use this newly derived set for future layered-Earth seismo-electromagnetic modelling experiments.

Description: The cancer genome is abnormal genome, and the ability to monitor its sequence had undergone a technological revolution. Yet prognosis and diagnosis remain an expert-based decision, with only limited abilities to provide machine-based decisions. We introduce a heterogeneity-based method for stratifying and visualizing whole-genome sequencing (WGS) reads. This method uses the heterogeneity within WGS reads to markedly reduce the dimensionality of next-generation sequencing data; it is available through the tool HiBS (Heterogeneity-Based Subclassification) that allows cancer sample classification. We validated HiBS using 〉200 WGS samples from nine different cancer types from The Cancer Genome Atlas (TCGA). With HiBS, we show progress with two WGS related issues: (i) differentiation between normal (NB) and tumor (TP) samples based solely on the information structure of their WGS data, and (ii) identification of specific regions of chromosomal amplification/deletion and their association with tumor stage. By comparing results to those obtained through available WGS analyses tools, we demonstrate some of the novelties obtained by the approach implemented in HiBS and also show nearly perfect normal/tumor classification, used to identify known and unknown chromosomal aberrations. Finally, the HiBS index has been associated with breast cancer tumor stage.

Description: Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/ .

Description: Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3'UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions.

Description: Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest. Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well. Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration.

Description: The Quaternary Añavieja-Dévanos tufa system is located in the northern sector of the Iberian Chain. It has been previously tackled by means sedimentological studies focused on the available outcrops and some boreholes. They have permitted the proposal of a sedimentary scenario that fits with a pool-barrage fluvial tufa model. However a better knowledge of the characteristics and internal distribution of the usually non-outcropping pool deposits as well as of its relationship with barrage deposits has not been evaluated in detail yet. Palaeoenvironmental studies on tufas are usually biased because tufas are commonly delicate facies exposed to intense erosion during water level fall stages; for this reason outcrops are usually scarce and very often coincide with the most cemented barrage deposits. In order to analyse the internal characteristics of the tufa deposits under study, but also the lateral correlation among different facies, ground penetrating radar (GPR) has been employed both for the evaluation of its applicability in such kind of environments and to improve, if possible, the sedimentary model using geophysical data in sectors without outcrops. A GPR survey including different antennas ranging from 50 to 500 MHz along different sectors and its comparison with natural outcrops has been carried out. GPR results have permitted to deduce clear differences between pool and barrage deposits and to recognise its internal structure and geometrical relationships. The survey also permitted an approach to different scales of heterogeneities in the radarfacies evaluation by using distinct antennas and therefore, reaching different resolutions and penetrations. The resulting integration from different antennas allows three different attenuant and eight reflective radarfacies to be defined permitting a better approach to the real extension of the pool areas. These results have permitted to decipher the horizontal and vertical facies changes and the identification of a scarcer development of pool deposits than expected in the studied system.

Description: CircRNAs are novel members of the non-coding RNA family. For several decades circRNAs have been known to exist, however only recently the widespread abundance has become appreciated. Annotation of circRNAs depends on sequencing reads spanning the backsplice junction and therefore map as non-linear reads in the genome. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. By this approach, we observe surprisingly dramatic differences between the algorithms specifically regarding the highly expressed circRNAs and the circRNAs derived from proximal splice sites. Collectively, this study emphasizes that circRNA annotation should be handled with care and that several algorithms should ideally be combined to achieve reliable predictions.

Description: Two novel transient controlled source electromagnetic methods called circular electrical dipole (CED) and differential electrical dipole (DED) are theoretically analysed for applications in shallow marine environments. 1-D and 3-D time-domain modelling studies are used to investigate the detectability and applicability of the methods when investigating resistive layers/targets representing hydrocarbon-saturated formations. The results are compared to the conventional time-domain horizontal electrical dipole (HED) and vertical electrical dipole (VED) sources. The applied theoretical modelling studies demonstrate that CED and DED have higher signal detectability towards resistive targets compared to TD-CSEM, but demonstrate significantly poorer signal amplitudes. Future CED/DED applications will have to solve this issue prior to measuring. Furthermore, the two novel methods have very similar detectability characteristics towards 3-D resistive targets embedded in marine sediments as VED while being less susceptible towards non-verticality. Due to the complex transmitter design of CED/DED the systems are prone to geometrical errors. Modelling studies show that even small transmitter inaccuracies have strong effects on the signal characteristics of CED making an actual marine application difficult at the present time. In contrast, the DED signal is less affected by geometrical errors in comparison to CED and may therefore be more adequate for marine applications.

Description: We explore Earth's elastic deformation response to ocean tidal loading (OTL) using kinematic Global Positioning System (GPS) observations and forward-modelled predictions across South America. Harmonic coefficients are extracted from up to 14 yr of GPS-inferred receiver locations, which we estimate at 5 min intervals using precise point positioning. We compare the observed OTL-induced surface displacements against predictions derived from spherically symmetric, non-rotating, elastic and isotropic (SNREI) Earth models. We also compare sets of modelled predictions directly for various ocean-tide and Earth-model combinations. The vector differences between predicted displacements computed using separate ocean-tide models reveal uniform-displacement components common to all stations in the South America network. Removal of the network-mean OTL-induced displacements from each site substantially reduces the vector differences between observed and predicted displacements. We focus on the dominant astronomical tidal harmonics from three distinct frequency bands: semidiurnal (M 2 ), diurnal (O 1 ) and fortnightly (M f ). In each band, the observed OTL-induced surface displacements strongly resemble the modelled displacement-response patterns, and the residuals agree to about 0.3 mm or better. Even with the submillimetre correspondence between observations and predictions, we detect regional-scale spatial coherency in the final set of residuals, most notably for the M 2 harmonic. The spatial coherency appears relatively insensitive to the specific choice of ocean-tide or SNREI-Earth model. Varying the load model or 1-D elastic structure yields predicted OTL-induced displacement differences of order 0.1 mm or less for the network. Furthermore, estimates of the observational uncertainty place the noise level below the magnitude of the residual displacements for most stations, supporting our interpretation that random errors cannot account for the entire misfit. Therefore, the spatially coherent residuals may reveal deficiencies in the a priori SNREI Earth models. In particular, the residuals may indicate sensitivity to regional deviations from standard globally averaged Earth structure due to the presence of the South American craton.

Description: An L-configured, three-component short period seismic array was deployed on the Ross Ice Shelf, Antarctica during November 2014. Polarization analysis of ambient noise data from these stations shows linearly polarized waves for frequency bands between 0.2 and 2 Hz. A spectral peak at about 1.6 Hz is interpreted as the resonance frequency of the water column and is used to estimate the water layer thickness below the ice shelf. The frequency band from 4 to 18 Hz is dominated by Rayleigh and Love waves propagating from the north that, based on daily temporal variations, we conclude were generated by field camp activity. Frequency–slowness plots were calculated using beamforming. Resulting Love and Rayleigh wave dispersion curves were inverted for the shear wave velocity profile within the firn and ice to ~150 m depth. The derived density profile allows estimation of the pore close-off depth and the firn–air content thickness. Separate inversions of Rayleigh and Love wave dispersion curves give different shear wave velocity profiles within the firn. We attribute this difference to an effective anisotropy due to fine layering. The layered structure of firn, ice, water and the seafloor results in a characteristic dispersion curve below 7 Hz. Forward modelling the observed Rayleigh wave dispersion curves using representative firn, ice, water and sediment structures indicates that Rayleigh waves are observed when wavelengths are long enough to span the distance from the ice shelf surface to the seafloor. The forward modelling shows that analysis of seismic data from an ice shelf provides the possibility of resolving ice shelf thickness, water column thickness and the physical properties of the ice shelf and underlying seafloor using passive-source seismic data.

Description: We present an algorithm to recover the Bayesian posterior model probability density function of subsurface elastic parameters, as required by the full pressure field recorded at an ocean bottom cable due to an impulsive seismic source. Both the data noise and source wavelet are estimated by our algorithm, resulting in robust estimates of subsurface velocity and density. In contrast to purely gradient based approaches, our method avoids model regularization entirely and produces an ensemble of models that can be visualized and queried to provide meaningful information about the sensitivity of the data to the subsurface, and the level of resolution of model parameters. Our algorithm is trans-dimensional and performs model selection, sampling over a wide range of model parametrizations. We follow a frequency domain approach and derive the corresponding likelihood in the frequency domain. We present first a synthetic example of a reservoir at 2 km depth with minimal acoustic impedance contrast, which is difficult to study with conventional seismic amplitude versus offset changes. Finally, we apply our methodology to survey data collected over the Alba field in the North Sea, an area which is known to show very little lateral heterogeneity but nevertheless presents challenges for conventional post migration seismic amplitude versus offset analysis.

Description: Background: Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection. Results: Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation. Conclusion: Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates.

Description: A novel application of seismic interferometry (SI) and Marchenko imaging using both surface and borehole data is presented. A series of redatuming schemes is proposed to combine both data sets for robust deep local imaging in the presence of velocity uncertainties. The redatuming schemes create a virtual acquisition geometry where both sources and receivers lie at the horizontal borehole level, thus only a local velocity model near the borehole is needed for imaging, and erroneous velocities in the shallow area have no effect on imaging around the borehole level. By joining the advantages of SI and Marchenko imaging, a macrovelocity model is no longer required and the proposed schemes use only single-component data. Furthermore, the schemes result in a set of virtual data that have fewer spurious events and internal multiples than previous virtual source redatuming methods. Two numerical examples are shown to illustrate the workflow and to demonstrate the benefits of the method. One is a synthetic model and the other is a realistic model of a field in the North Sea. In both tests, improved local images near the boreholes are obtained using the redatumed data without accurate velocities, because the redatumed data are close to the target.

Description: Planar faults are widely adopted during inversions to determine slip distributions and fault geometries using geodetic observations; however, little research has been conducted with respect to curved faults. We attribute this to the lack of an appropriate parameterized modelling method. In this paper, we present a curved-fault modelling method (CFMM) that describes a curved fault according to specific parameters, and we also develop a corresponding hybrid iterative inversion algorithm (HIIA) to perform inversions for parametric curved-fault geometries and slips. The results of the strike-component and dip-component synthetic tests show that a complex S-shaped fault surface and a circular slip distribution are successfully recovered, indicating the strong performance of the CFMM and HIIA methods. In addition, we describe and verify a scenario for determining the number of necessary geometrical parameters for the HIIA and examine the case study of the Wenchuan earthquake, which occurred on a complex listric fault surface. During the iteration process of the HIIA, both the fault geometry and slip distribution of the Beichuan and Pengguan faults converge to optimal values, indicating a Beichuan fault (BCF) model with a continuous listric shape and gradual steepening from the southwest to the northeast, which is highly consistent with geological survey results. Both the synthetic and real-world case studies show that the HIIA and the CMFF are superior to the conventional fault modelling method based on rectangular planes and that these models have the potential for use in more integrated research involving inversion studies, such as joint slip/curved-fault-geometry inversions that take into account data resolving power.

Description: Regulatory DNA elements, short genomic segments that regulate gene expression, have been implicated in developmental disorders and human disease. Despite this clinical urgency, only a small fraction of the regulatory DNA repertoire has been confirmed through reporter gene assays. The overall success rate of functional validation of candidate regulatory elements is low. Moreover, the number and diversity of datasets from which putative regulatory elements can be identified is large and rapidly increasing. We generated a flexible and user-friendly tool to integrate the information from different types of genomic datasets, e.g. ATAC-seq, ChIP-seq, conservation, aiming to increase the ease and success rate of functional prediction. To this end, we developed the EMERGE program that merges all datasets that the user considers informative and uses a logistic regression framework, based on validated functional elements, to set optimal weights to these datasets. ROC curve analysis shows that a combination of datasets leads to improved prediction of tissue-specific enhancers in human, mouse and Drosophila genomes. Functional assays based on this prediction can be expected to have substantially higher success rates. The resulting integrated signal for prediction of functional elements can be plotted in a build-in genome browser or exported for further analysis.

Description: Regulation of gene expression requires both transcription factor (TFs) and epigenetic modifications, and interplays between the two types of factors have been discovered. However study of relationships between chromatin features and TF–TF co-occupancy remains limited. Here, we revealed the relationship by first illustrating distinct profile patterns of chromatin features related to different binding events, including single TF binding and TF–TF co-occupancy of 71 TFs from five human cell lines. We further implemented statistical analyses to demonstrate the relationship by accurately predicting co-occupancy genome-widely using chromatin features including DNase I hypersensitivity, 11 histone modifications (HMs) and GC content. Remarkably, our results showed that the combination of chromatin features enables accurate predictions across the five cells. For individual chromatin features, DNase I enables high and consistent predictions. H3K27ac, H3K4me 2, H3K4me3 and H3K9ac are more reliable predictors than other HMs. Although the combination of 11 HMs achieves accurate predictions, their predictive ability varies considerably when a model obtained from one cell is applied to others, indicating relationship between HMs and TF–TF co-occupancy is cell type dependent. GC content is not a reliable predictor, but the addition of GC content to any other features enhances their predictive ability. Together, our results elucidate a strong relationship between TF–TF co-occupancy and chromatin features.

Description: The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co-localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover ‘functional 3D hotspots’, regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P -value contains MSB2 and ERG11 – known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k -Nearest Neighbor ( k -NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions.

Description: Hidden Markov models (HMMs) have been extensively used to dissect the genome into functionally distinct regions using data such as RNA expression or DNA binding measurements. It is a challenge to disentangle processes occurring on complementary strands of the same genomic region. We present the double-stranded HMM (dsHMM), a model for the strand-specific analysis of genomic processes. We applied dsHMM to yeast using strand specific transcription data, nucleosome data, and protein binding data for a set of 11 factors associated with the regulation of transcription.The resulting annotation recovers the mRNA transcription cycle (initiation, elongation, termination) while correctly predicting strand-specificity and directionality of the transcription process. We find that pre-initiation complex formation is an essentially undirected process, giving rise to a large number of bidirectional promoters and to pervasive antisense transcription. Notably, 12% of all transcriptionally active positions showed simultaneous activity on both strands. Furthermore, dsHMM reveals that antisense transcription is specifically suppressed by Nrd1, a yeast termination factor.

Description: Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) is widely used to identify binding sites for a target protein in the genome. An important scientific application is to identify changes in protein binding between different treatment conditions, i.e. to detect differential binding. This can reveal potential mechanisms through which changes in binding may contribute to the treatment effect. The csaw package provides a framework for the de novo detection of differentially bound genomic regions. It uses a window-based strategy to summarize read counts across the genome. It exploits existing statistical software to test for significant differences in each window. Finally, it clusters windows into regions for output and controls the false discovery rate properly over all detected regions. The csaw package can handle arbitrarily complex experimental designs involving biological replicates. It can be applied to both transcription factor and histone mark datasets, and, more generally, to any type of sequencing data measuring genomic coverage. csaw performs favorably against existing methods for de novo DB analyses on both simulated and real data. csaw is implemented as a R software package and is freely available from the open-source Bioconductor project.

Description: Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of micro-evolution. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method's wide applicability by testing it on multiple cases of micro-evolution. We show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens.