ALBERT

Description: In this study, information carried by the ambient seismic field is exploited to extract impulse response functions between two seismic stations using one as a ‘virtual’ source. Interferometry by deconvolution method is used and validated by comparing the extracted ambient noise impulse response waveforms with records of moderate magnitude earthquakes (from M w 4 to 5.8) that occurred close to the virtual source station in Japan. As the information is only available at low frequencies (less than 0.25 Hz), the ambient seismic field approach is coupled to a non-stationary stochastic model to simulate time domain accelerograms up to 50 Hz. This coupling allows the predicted ground motion to have both the deterministic part at low frequencies coming from the source and the crust structure and the high-frequency random contribution from the seismic waves scattering. The resulting combined accelerograms for an M w 5.8 event show a good agreement with observed ground motions from a real earthquake.

Description: Targeted resequencing technologies have allowed for efficient and cost-effective detection of genomic variants in specific regions of interest. Although capture sequencing has been primarily used for investigating single nucleotide variants and indels, it has the potential to elucidate a broader spectrum of genetic variation, including copy number variants (CNVs). Various methods exist for detecting CNV in whole-genome and exome sequencing datasets. However, no algorithms have been specifically designed for contiguous target sequencing, despite its increasing importance in clinical and research applications. We have developed cnvCapSeq, a novel method for accurate and sensitive CNV discovery and genotyping in long-range targeted resequencing. cnvCapSeq was benchmarked using a simulated contiguous capture sequencing dataset comprising 21 genomic loci of various lengths. cnvCapSeq was shown to outperform the best existing exome CNV method by a wide margin both in terms of sensitivity (92.0 versus 48.3%) and specificity (99.8 versus 70.5%). We also applied cnvCapSeq to a real capture sequencing cohort comprising a contiguous 358 kb region that contains the Complement Factor H gene cluster. In this dataset, cnvCapSeq identified 41 samples with CNV, including two with duplications, with a genotyping accuracy of 99%, as ascertained by quantitative real-time PCR.

Description: On 2012 May 19, an m b  = 4 earthquake shook the town of Montes Claros, Brazil in the middle of the São Francisco Craton. Because of the scarce seismicity in the area, an event like this could provide valuable information to characterize the governing seismotectonics and stress field for the region. Here, we present the results of more than 1 yr of local seismic monitoring after the main shock. We found that the seismicity originated at approximately 1-km depth in an NNW-oriented blind reverse fault, dipping to the E. The magnitude of the main shock was 4 m b , with aftershocks reaching up to 3.6 m b . Focal mechanisms from first motion polarities and waveform moment tensor inversions indicate a reverse faulting in agreement with the orientation of the aftershock locations. In addition, we derived a new 1-D local velocity model using a simultaneous inversion of hypocentres and velocity layers. The results indicate P -wave velocities of 4.5 km s –1 for the upper layer of carbonate rocks and 5.23 and 5.69 km s –1 for the lower fractured and compact crystalline basement layers, respectively. Higher Vp / Vs ratios were obtained for the upper two layers compared to the lowermost layer, possibly indicating presence of rock fracturing and percolated water. The calculated stress drop for the main event is 0.33 MPa, which is a relatively low value for an intraplate earthquake but still within the observed range. The inversion of the main shock focal mechanism and previously published focal mechanisms suggests a compressional stress regime in the central part of the São Francisco Craton, which is different from the strike-slip regime in the southern part, although both have an EW-oriented 1. On the other hand, focal mechanisms of events located to the west of the craton indicate an NW–SE oriented 1 for central Brazil. This variability highlights the importance of local sources of stresses (e.g. flexural stresses) in mid-plate South America, unlike other mid-plate areas of the world, such as central and east North America, where a more uniform stress field is observed.

Description: The Paradox Valley Unit (PVU), a salinity control project in southwest Colorado, disposes of brine in a single deep injection well. Since the initiation of injection at the PVU in 1991, earthquakes have been repeatedly induced. PVU closely monitors all seismicity in the Paradox Valley region with a dense surface seismic network. A key factor for understanding the seismic hazard from PVU injection is the maximum magnitude earthquake that can be induced. The estimate of maximum magnitude of induced earthquakes is difficult to constrain as, unlike naturally occurring earthquakes, the maximum magnitude of induced earthquakes changes over time and is affected by injection parameters. We investigate temporal variations in maximum magnitudes of induced earthquakes at the PVU using two methods. First, we consider the relationship between the total cumulative injected volume and the history of observed largest earthquakes at the PVU. Second, we explore the relationship between maximum magnitude and the geometry of individual seismicity clusters. Under the assumptions that: (i) elevated pore pressures must be distributed over an entire fault surface to initiate rupture and (ii) the location of induced events delineates volumes of sufficiently high pore-pressure to induce rupture, we calculate the largest allowable vertical penny-shaped faults, and investigate the potential earthquake magnitudes represented by their rupture. Results from both the injection volume and geometrical methods suggest that the PVU has the potential to induce events up to roughly M W 5 in the region directly surrounding the well; however, the largest observed earthquake to date has been about a magnitude unit smaller than this predicted maximum. In the seismicity cluster surrounding the injection well, the maximum potential earthquake size estimated by these methods and the observed maximum magnitudes have remained steady since the mid-2000s. These observations suggest that either these methods overpredict maximum magnitude for this area or that long time delays are required for sufficient pore-pressure diffusion to occur to cause rupture along an entire fault segment. We note that earthquake clusters can initiate and grow rapidly over the course of 1 or 2 yr, thus making it difficult to predict maximum earthquake magnitudes far into the future. The abrupt onset of seismicity with injection indicates that pore-pressure increases near the well have been sufficient to trigger earthquakes under pre-existing tectonic stresses. However, we do not observe remote triggering from large teleseismic earthquakes, which suggests that the stress perturbations generated from those events are too small to trigger rupture, even with the increased pore pressures.

Description: Cancers are heterogeneous and genetically unstable. New methods are needed that provide the sensitivity and specificity to query single cells at the genetic loci that drive cancer progression, thereby enabling researchers to study the progression of individual tumors. Here, we report the development and application of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to achieve ‘quantitative’ measurement and single-molecule sequencing of somatically acquired carcinogenic translocations at extremely low levels (〈10 –6 ) in healthy subjects. We use this technique in our healthy study population to determine the overall concentration of the t(14;18) translocation, which is strongly associated with follicular lymphoma. The nested dPCR approach improves the detection limit to 1 x 10 –7 or lower while maintaining the analysis efficiency and specificity. Further, the bead-based dPCR enabled us to isolate and quantify the relative amounts of the various clonal forms of t(14;18) translocation in these subjects, and the single-molecule sensitivity and resolution of dPCR led to the discovery of new clonal forms of t(14;18) that were otherwise masked by the conventional quantitative PCR measurements. In this manner, we created a quantitative map for this carcinogenic mutation in this healthy population and identified the positions on chromosomes 14 and 18 where the vast majority of these t(14;18) events occur.

Description: Life abounds with genetic variations writ in sequences that are often only a few hundred nucleotides long. Rapid detection of these variations for identification of genetic diseases, pathogens and organisms has become the mainstay of molecular science and medicine. This report describes a new, highly informative closed-tube polymerase chain reaction (PCR) strategy for analysis of both known and unknown sequence variations. It combines efficient quantitative amplification of single-stranded DNA targets through LATE-PCR with sets of Lights-On/Lights-Off probes that hybridize to their target sequences over a broad temperature range. Contiguous pairs of Lights-On/Lights-Off probes of the same fluorescent color are used to scan hundreds of nucleotides for the presence of mutations. Sets of probes in different colors can be combined in the same tube to analyze even longer single-stranded targets. Each set of hybridized Lights-On/Lights-Off probes generates a composite fluorescent contour, which is mathematically converted to a sequence-specific fluorescent signature. The versatility and broad utility of this new technology is illustrated in this report by characterization of variant sequences in three different DNA targets: the rpoB gene of Mycobacterium tuberculosis, a sequence in the mitochondrial cytochrome C oxidase subunit 1 gene of nematodes and the V3 hypervariable region of the bacterial 16 s ribosomal RNA gene. We anticipate widespread use of these technologies for diagnostics, species identification and basic research.

Description: Current earthquake early warning (EEW) systems lack the ability to appropriately handle multiple concurrent earthquakes, which led to many false alarms during the 2011 Tohoku earthquake sequence in Japan. This paper uses a Bayesian probabilistic approach to handle multiple concurrent events for EEW. We implement the theory using a two-step algorithm. First, an efficient approximate Bayesian model class selection scheme is used to estimate the number of concurrent events. Then, the Rao-Blackwellized Importance Sampling method with a sequential proposal probability density function is used to estimate the earthquake parameters, that is hypocentre location, origin time, magnitude and local seismic intensity. A real data example based on 2 months data (2011 March 9–April 30) around the time of the 2011 M 9 Tohoku earthquake is studied to verify the proposed algorithm. Our algorithm results in over 90 per cent reduction in the number of incorrect warnings compared to the existing EEW system operating in Japan.

Description: The effect of network density and geometric distribution on kinematic non-linear source inversion is investigated by inverting synthetic ground motions from a buried strike-slip fault ( M w 6.5), that have been generated by dynamic spontaneous rupture modelling. For the inversion, we use a physics-based regularized Yoffe function as slip velocity function. We test three different cases of station network geometry: (i) single station, varying azimuth and epicentral distance; (ii) multistation circular configurations, that is stations at similar distances from the fault, and regularly spaced around the fault; (iii) irregular multistation configurations using different numbers of stations. Our results show: (1) single station tests suggest that it may be possible to obtain a relatively good source model even using a single station. The best source model using a single station is obtained with stations at which amplitude ratios between three components are not large. We infer that both azimuthal angle and source-to-station distance play an important role in the design of optimal seismic network for source inversion. (2) Multistation tests show that the quality of the inverted source systematically correlates neither with the number of stations, nor with waveform misfit. (3) Waveform misfit has a direct correlation with the number of stations, resulting in overfitting the observed data without any systematic improvement of the source. It suggests that the best source model is not necessarily derived from the model with minimum waveform misfit. (4) A seismic network with a small number of well-spaced stations around the fault may be sufficient to obtain acceptable source inversion.

Description: The ‘Random Mutation Capture’ assay allows for the sensitive quantitation of DNA mutations at extremely low mutation frequencies. This method is based on PCR detection of mutations that render the mutated target sequence resistant to restriction enzyme digestion. The original protocol prescribes an end-point dilution to about 0.1 mutant DNA molecules per PCR well, such that the mutation burden can be simply calculated by counting the number of amplified PCR wells. However, the statistical aspects associated with the single molecular nature of this protocol and several other molecular approaches relying on binary (on/off) output can significantly affect the quantification accuracy, and this issue has so far been ignored. The present work proposes a design of experiment (DoE) using statistical modeling and Monte Carlo simulations to obtain a statistically optimal sampling protocol, one that minimizes the coefficient of variance in the measurement estimates. Here, the DoE prescribed a dilution factor at about 1.6 mutant molecules per well. Theoretical results and experimental validation revealed an up to 10-fold improvement in the information obtained per PCR well, i.e. the optimal protocol achieves the same coefficient of variation using one-tenth the number of wells used in the original assay. Additionally, this optimization equally applies to any method that relies on binary detection of a small number of templates.

Description: The Maule earthquake (2010 February 27, M w 8.8, Chile) broke the subduction megathrust along a previously locked segment. Based on an international aftershock deployment, catalogues of precisely located aftershocks have become available. Using 23 well-located aftershocks, we calibrate the classic teleseismic backprojection procedure to map the high-frequency seismic radiation emitted during the earthquake. The calibration corrects traveltimes in a standard earth model both with a static term specific to each station, and a ‘dynamic’ term specific to each combination of grid point and station. The second term has been interpolated over the whole slipping area by kriging, and is about an order of magnitude smaller than the static term. This procedure ensures that the teleseismic images of rupture development are properly located with respect to aftershocks recorded with local networks and does not depend on accurate hypocentre location of the main shock. We track a bilateral rupture propagation lasting ~160 s, with its dominant branch rupturing northeastwards at about 3 km s –1 . The area of maximum energy emission is offset from the maximum coseismic slip but matches the zone where most plate interface aftershocks occur. Along dip, energy is preferentially released from two disconnected interface belts, and a distinct jump from the shallower belt to the deeper one is visible after about 20 s from the onset. However, both belts keep on being active until the end of the rupture. These belts approximately match the position of the interface aftershocks, which are split into two clusters of events at different depths, thus suggesting the existence of a repeated transition from stick-slip to creeping frictional regime.