ALBERT

Description: We present the crustal resistivity structure of the Pamir and Southern Tian Shan orogenic belts at the northwestern promontory of the India–Asia collision zone. The magnetotelluric (MT) data were recorded along a roughly north–south trending, 350 km long corridor from the Pamir Plateau in southern Tajikistan across the Pamir frontal ranges, the Alai Valley and the southwestern Tian Shan to Osh in the Kyrgyz part of the Fergana Basin. In total, we measured at 178 sites, whereof 26 combine broad band and long period recordings. One of the most intriguing features of the 2-D and 3-D inversion results is a laterally extended zone of high electrical conductivity below the Pamir Plateau, with resistivities below 1 m, starting at a depth of ~10–15 km. The high conductivity can be explained with the presence of partially molten rocks at middle to lower crustal levels, possibly related to ongoing migmatization and/or middle/lower crustal flow underneath the Southern Pamir. This interpretation is consistent with a low velocity zone found from local earthquake tomography, relatively high v p / v s ratios, elevated surface heat flow, and thermomechanical modelling suggesting that melting temperatures are reached in the felsic middle crust. In the upper crust of the Pamir and Tian Shan, the Palaeozoic–Mesozoic suture zones appear as electrically conductive, whereas the compact metamorphic rocks of the Muskol-Shatput Dome of the Central Pamir are highly resistive. The intra-montane basin of the Alai Valley—sandwiched between the Pamir and Tian Shan—exhibits a generally conductive upper crust that bifurcates into two conductors at depth. One of them connects to the active Main Pamir Thrust, which is absorbing most of today's convergence between the Pamir and the Tian Shan. Several deeper zones of high conductivity in the middle and lower crust of Central and Northern Pamir likely record fluid release due to metamorphism associated with active continental subduction/delamination.

Description: One of the benefits of Digital PCR (dPCR) is the potential for unparalleled precision enabling smaller fold change measurements. An example of an assessment that could benefit from such improved precision is the measurement of tumour-associated copy number variation (CNV) in the cell free DNA (cfDNA) fraction of patient blood plasma. To investigate the potential precision of dPCR and compare it with the established technique of quantitative PCR (qPCR), we used breast cancer cell lines to investigate HER2 gene amplification and modelled a range of different CNVs. We showed that, with equal experimental replication, dPCR could measure a smaller CNV than qPCR. As dPCR precision is directly dependent upon both the number of replicate measurements and the template concentration, we also developed a method to assist the design of dPCR experiments for measuring CNV. Using an existing model (based on Poisson and binomial distributions) to derive an expression for the variance inherent in dPCR, we produced a power calculation to define the experimental size required to reliably detect a given fold change at a given template concentration. This work will facilitate any future translation of dPCR to key diagnostic applications, such as cancer diagnostics and analysis of cfDNA.

Description: Geophysical data are the main source of information about the subsurface. Geophysical techniques are, however, highly non-unique in determining specific physical parameters and boundaries of subsurface objects. To obtain actual physical information, an inversion process is often applied, in which measurements at or above the Earth surface are inverted into a 2- or 3-D subsurface spatial distribution of the physical property. Interpreting these models into structural objects, related to physical processes, requires a priori knowledge and expert analysis which is susceptible to subjective choices and is therefore often non-repeatable. In this research, we implemented a recently introduced object-based approach to interpret the 3-D inversion results of a single geophysical technique using the available a priori information and the physical and geometrical characteristics of the interpreted objects. The introduced methodology is semi-automatic and repeatable, and allows the extraction of subsurface structures using 3-D object-oriented image analysis (3-D OOA) in an objective knowledge–based classification scheme. The approach allows for a semi-objective setting of thresholds that can be tested and, if necessary, changed in a very fast and efficient way. These changes require only changing the thresholds used in a so-called ruleset, which is composed of algorithms that extract objects from a 3-D data cube. The approach is tested on a synthetic model, which is based on a priori knowledge on objects present in the study area (Tanzania). Object characteristics and thresholds were well defined in a 3-D histogram of velocity versus depth, and objects were fully retrieved. The real model results showed how 3-D OOA can deal with realistic 3-D subsurface conditions in which the boundaries become fuzzy, the object extensions become unclear and the model characteristics vary with depth due to the different physical conditions. As expected, the 3-D histogram of the real data was substantially more complex. Still, the 3-D OOA-derived objects were extracted based on their velocity and their depth location. Spatially defined boundaries, based on physical variations, can improve the modelling with spatially dependent parameter information. With 3-D OOA, the non-uniqueness on the location of objects and their physical properties can be potentially significantly reduced.

Description: MiST is a novel approach to variant calling from deep sequencing data, using the inverted mapping approach developed for Geoseq. Reads that can map to a targeted exonic region are identified using exact matches to tiles from the region. The reads are then aligned to the targets to discover variants. MiST carefully handles paralogous reads that map ambiguously to the genome and clonal reads arising from PCR bias, which are the two major sources of errors in variant calling. The reduced computational complexity of mapping selected reads to targeted regions of the genome improves speed, specificity and sensitivity of variant detection. Compared with variant calls from the GATK platform, MiST showed better concordance with SNPs from dbSNP and genotypes determined by an exonic-SNP array. Variant calls made only by MiST confirm at a high rate (〉90%) by Sanger sequencing. Thus, MiST is a valuable alternative tool to analyse variants in deep sequencing data.

Description: We use continuous GPS measurements from 31 stations in southern Mexico to model coseismic slip and post-seismic deformation from the 2012 March 20 M w  = 7.5 Ometepec earthquake, the first large thrust earthquake to occur below central Mexico during the modern GPS era. Coseismic offsets ranging from ~280 mm near the epicentre to 5 mm or less at sites far from the epicentre are fit best by a rupture focused between ~15 and 35 km depth, consistent with an independent seismological estimate. The corresponding geodetic moment of 1.4 10 20 N·m is within 10 per cent of two independent seismic estimates. Transient post-seismic motion recorded by GPS sites as far as 300 km from the rupture has a different horizontal deformation gradient and opposite sense of vertical motion than do the coseismic offsets. A forward model of viscoelastic relaxation as a result of our new coseismic slip solution incorrectly predicts uplift in areas where post-seismic subsidence was recorded and indicates that viscoelastic deformation was no more than a few per cent of the measured post-seismic deformation. The deformation within 6 months of the earthquake was thus strongly dominated by fault afterslip. The post-seismic GPS time-series are well fit as logarithmically decaying fault afterslip on an area of the subduction interface up to 10 times larger than the earthquake rupture zone, extending as far as 220 km inland. Afterslip had a cumulative geodetic moment of 2.0 10 20 N·m, ~40 per cent larger than the Ometepec earthquake. Tests for the shallow and deep limits for the afterslip require that it included much of the earthquake rupture zone as well as regions of the subduction interface where slow slip events and non-volcanic tremor have been recorded and areas even farther downdip on the flat interface. Widespread afterslip below much of central Mexico suggests that most of the nearly flat subduction interface in this region is conditionally stable and thus contributes measurable transient deformation to large areas of Mexico south of and in the volcanic belt.

Description: Sequencing of RNAs (RNA-Seq) has revolutionized the field of transcriptomics, but the reads obtained often contain errors. Read error correction can have a large impact on our ability to accurately assemble transcripts. This is especially true for de novo transcriptome analysis, where a reference genome is not available. Current read error correction methods, developed for DNA sequence data, cannot handle the overlapping effects of non-uniform abundance, polymorphisms and alternative splicing. Here we present SEquencing Error CorrEction in Rna-seq data (SEECER), a hidden Markov Model (HMM)–based method, which is the first to successfully address these problems. SEECER efficiently learns hundreds of thousands of HMMs and uses these to correct sequencing errors. Using human RNA-Seq data, we show that SEECER greatly improves on previous methods in terms of quality of read alignment to the genome and assembly accuracy. To illustrate the usefulness of SEECER for de novo transcriptome studies, we generated new RNA-Seq data to study the development of the sea cucumber Parastichopus parvimensis . Our corrected assembled transcripts shed new light on two important stages in sea cucumber development. Comparison of the assembled transcripts to known transcripts in other species has also revealed novel transcripts that are unique to sea cucumber, some of which we have experimentally validated. Supporting website: http://sb.cs.cmu.edu/seecer/ .

Description: The 3-D shear velocity structure beneath South India's Dharwar Craton determined from fundamental mode Rayleigh waves phase velocities reveals the existence of anomalously high velocity materials in the depth range of 50–100 km. Tomographic analysis of seismograms recorded on a network of 35 broad-band seismographs shows the uppermost mantle shear wave speeds to be as high as 4.9 km s –1 in the northwestern Dharwar Craton, decreasing both towards the south and the east. Below ~100 km, the shear wave speed beneath the Dharwar Craton is close to the global average shear wave speed at these depths. Limitations of usable Rayleigh phase periods, however, have restricted the analysis to depths of 120 km, precluding the delineation of the lithosphere–asthenosphere boundary in this region. However, pressure–temperature analysis of xenoliths in the region suggests a lithospheric thickness of at least ~185 km during the mid-Proterozoic period. The investigations were motivated by a search for seismic indicators in the shallow mantle beneath the distinctly different parts of the Dharwar Craton otherwise distinguished by their lithologies, ages and crustal structure. Since the ages of cratonic crust and of the associated mantle lithosphere around the globe have been found to be broadly similar and their compositions bimodal in time, any distinguishing features of the various parts of the Dharwar shallow mantle could thus shed light on the craton formation process responsible for stabilizing the craton during the Meso- and Neo-Archean.

Description: Described in the article is a new approach for the sequence-specific detection of nucleic acids in real-time polymerase chain reaction (PCR) using fluorescently labeled oligonucleotide probes. The method is based on the production of PCR amplicons, which fold into dumbbell-like secondary structures carrying a specially designed ‘probe-luring’ sequence at their 5' ends. Hybridization of this sequence to a complementary ‘anchoring’ tail introduced at the 3' end of a fluorescent probe enables the probe to bind to its target during PCR, and the subsequent probe cleavage results in the florescence signal. As it has been shown in the study, this amplicon-endorsed and guided formation of the probe-target duplex allows the use of extremely short oligonucleotide probes, up to tetranucleotides in length. In particular, the short length of the fluorescent probes makes possible the development of a ‘universal’ probe inventory that is relatively small in size but represents all possible sequence variations. The unparalleled cost-effectiveness of the inventory approach is discussed. Despite the short length of the probes, this new method, named Angler real-time PCR, remains highly sequence specific, and the results of the study indicate that it can be effectively used for quantitative PCR and the detection of polymorphic variations.