ALBERT

Description: Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information. Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples.

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

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

Description: Data on biological mechanisms of aging are mostly obtained from cross-sectional study designs. An inherent disadvantage of this design is that inter-individual differences can mask small but biologically significant age-dependent changes. A serially sampled design (same individual at different time points) would overcome this problem but is often limited by the relatively small numbers of available paired samples and the statistics being used. To overcome these limitations, we have developed a new vector-based approach, termed three-component analysis, which incorporates temporal distance, signal intensity and variance into one single score for gene ranking and is combined with gene set enrichment analysis. We tested our method on a unique age-based sample set of human skin fibroblasts and combined genome-wide transcription, DNA methylation and histone methylation (H3K4me3 and H3K27me3) data. Importantly, our method can now for the first time demonstrate a clear age-dependent decrease in expression of genes coding for proteins involved in translation and ribosome function. Using analogies with data from lower organisms, we propose a model where age-dependent down-regulation of protein translation-related components contributes to extend human lifespan.

Description: A major challenge in the field of shotgun metagenomics is the accurate identification of organisms present within a microbial community, based on classification of short sequence reads. Though existing microbial community profiling methods have attempted to rapidly classify the millions of reads output from modern sequencers, the combination of incomplete databases, similarity among otherwise divergent genomes, errors and biases in sequencing technologies, and the large volumes of sequencing data required for metagenome sequencing has led to unacceptably high false discovery rates (FDR). Here, we present the application of a novel, gene-independent and signature-based metagenomic taxonomic profiling method with significantly and consistently smaller FDR than any other available method. Our algorithm circumvents false positives using a series of non-redundant signature databases and examines G enomic O rigins T hrough T axonomic CHA llenge (GOTTCHA). GOTTCHA was tested and validated on 20 synthetic and mock datasets ranging in community composition and complexity, was applied successfully to data generated from spiked environmental and clinical samples, and robustly demonstrates superior performance compared with other available tools.

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

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

Description: Chromosome-long haplotyping of human genomes is important to identify genetic variants with differing gene expression, in human evolution studies, clinical diagnosis, and other biological and medical fields. Although several methods have realized haplotyping based on sequencing technologies or population statistics, accuracy and cost are factors that prohibit their wide use. Borrowing ideas from group testing theories, we proposed a clone-based haplotyping method by overlapping pool sequencing. The clones from a single individual were pooled combinatorially and then sequenced. According to the distinct pooling pattern for each clone in the overlapping pool sequencing, alleles for the recovered variants could be assigned to their original clones precisely. Subsequently, the clone sequences could be reconstructed by linking these alleles accordingly and assembling them into haplotypes with high accuracy. To verify the utility of our method, we constructed 130 110 clones in silico for the individual NA12878 and simulated the pooling and sequencing process. Ultimately, 99.9% of variants on chromosome 1 that were covered by clones from both parental chromosomes were recovered correctly, and 112 haplotype contigs were assembled with an N50 length of 3.4 Mb and no switch errors. A comparison with current clone-based haplotyping methods indicated our method was more accurate.

Description: Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these ‘repressed transcripts’ have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies.