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  • Computational Methods, Genomics  (140)
  • 04. Solid Earth::04.06. Seismology::04.06.06. Surveys, measurements, and monitoring
  • 04.02. Exploration geophysics
  • 04.06. Seismology
  • JSTOR Archive Collection Business II
  • Oxford University Press  (161)
  • Wiley  (9)
  • Copernicus Publications  (8)
  • American Chemical Society (ACS)
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  • 1
    Publikationsdatum: 2024-04-03
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved.
    Beschreibung: Estimation of local seismic response plays a key role in assessing local seismic hazard and particularly in the design of shaking scenarios. Modelling local seismic response involves knowing of the shear wave velocity (Vs) and quality factor (Qs) profiles for the site in question. The many techniques that have been developed to assess Vs in surface deposits produce reliable measurements of Vs , but these rarely correspond to direct measurements of Qs . The latter is often considered through damping measures from laboratory tests on small-scale soil samples, which can provide information primarily on intrinsic attenuation, neglecting the contribution of scattering effects. In this paper, using seismic recordings obtained at the surface and in boreholes at 100 m depth, we estimate an average value of Qs of some characteristic alluvial deposits of the Po Plain (northern Italy). Data come from a microseismic network which sampled an almost uniform lithology in the central Po Plain and consisted of three surface and four borehole stations with an interstation distance of about 2 km. The average value of Qs of the shallowest 100 m of the sedimentary strata, Qs100, is estimated by considering: (1) the high-frequency attenuation of seismic waves due to propagation through the corresponding stratigraphy and (2) the interference between incident and surface-reflected waves observed at borehole stations. We parametrize the first through k0_100, the difference between the values of the spectral decay parameter kappa (k) estimated at the surface and at the boreholes depth, respectively. We use the second in order to compute Vs100, the time-averaged Vs referred to the uppermost 100 m stratigraphy. We obtain: k0_100 = (11 ± 3) ms, Vs100 = (309 ± 11) m s −1 and Qs100 = 31 ± 10. At the surface, the estimated values of the site-specific kappa, k0, are found to range from 75 to 79 ms. As expected, these results are in good agreement with studies performed in other sites characterized by sandy or clayey lithologies, and can be usefully used in site response analysis at sites where the rigidity is mainly controlled by lithostatic pressure.
    Beschreibung: Comune di Minerbio (grant: “Sperimentazione ILG Minerbio”; grant number: 0913.010).
    Beschreibung: Published
    Beschreibung: 2075–2094
    Beschreibung: OST2 Deformazione e Hazard sismico e da maremoto
    Beschreibung: JCR Journal
    Schlagwort(e): Earthquake ground motions ; Seismic attenuation ; Site effects ; Wave propagation ; Wave scattering and diffraction ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 2
    Publikationsdatum: 2024-02-07
    Beschreibung: A catalogue of precisely located micro-seismicity is fundamental for investigating seismicity and rock physical properties in active tectonic and volcanic regions and for the definition of a ‘baseline’ seismicity, required for a safe future exploitation of georesource areas. In this study, we produce the first manually revised catalogue of micro-seismicity for Co. Donegal region (Ireland), an area of about 50K M2 of on-going deformation, aimed at localizing natural micro-seismic events occurred between 2012 and 2015. We develop a stochastic method based on a Markov chain Monte Carlo (McMC) sampling approach to compute earthquake hypocentral location parameters. Our results indicates that micro-seismicity is present with magnitudes lower than 2 (the highest magnitude is 2.8).The recorded seismicity is almost clustered along previously mapped NE-SW trending, steeply dipping faults and confined within the upper crust (focal depth less than 10 km). We also recorded anthropogenic seismicity mostly related to quarries' activity in the study area.
    Beschreibung: Published
    Beschreibung: 62-76
    Beschreibung: OST1 Alla ricerca dei Motori Geodinamici
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 3
    Publikationsdatum: 2024-03-12
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved.
    Beschreibung: We present the results from a fully unconstrained moment tensor inversion of induced seismic events in a complex and high seismic hazard region (Val d’Agri basin, Southern Italy). The study area hosts two well-documented cases of induced microseismicity linked to (i) a wastewater injection well of a giant oilfield (the largest in onshore Europe), and (ii) severe seasonal level changes of an artificial lake. In order to gather information on the non-doublecouple components of the source and to better understand the rupture mechanisms, we analyse seismic events recorded during daily injection tests in the disposal well. The computed moment tensors have significant non-double-couple components that correlate with the well-head injection pressure. The injection parameters strongly influence the rupture mechanism that can be interpreted as due to the opening/closing of a fracture network inside a fault zone of a pre-existing thrust fault. For the case of the reservoir-induced seismicity, no direct correlations are observed with the loading/unloading of the reservoir.
    Beschreibung: Published
    Beschreibung: 1617–1627
    Beschreibung: OST3 Vicino alla faglia
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 4
    Publikationsdatum: 2024-05-09
    Beschreibung: To understand the seismic hazard of a subduction zone, it is necessary to know the geometry, location and mechanical characteristics of the interplate boundary below which an oceanic plate is thrust downward. By considering the azimuthal dependence of converted P-to-S (Ps) amplitudes in receiver functions, we have detected the interplate boundary in the Makran subduction zone, revealing significant seismic anisotropy at the base of the accretionary wedge above the slab before it bends down beneath the Jaz Murian basin. This anisotropic feature aligns with a zone of reduced seismic velocity and a high primary/secondary wave velocity ratio (Vp/Vs), as documented in previous studies. The presence of this low-velocity highly anisotropic layer at the base of the accretionary wedge, likely representing a low-strength shear zone, could possibly explain the unusually wide accretionary wedge in Makran. Additionally, it may impact the location and width of the locked zone along the interplate boundary.
    Beschreibung: Iranian National Science Foundation (INSF)
    Beschreibung: Published
    Beschreibung: 64-74
    Beschreibung: OST1 Alla ricerca dei Motori Geodinamici
    Beschreibung: JCR Journal
    Schlagwort(e): Earthquake hazards, Seismic anisotropy, Crustal structure, Subduction zone processes ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 5
    Publikationsdatum: 2022-03-07
    Beschreibung: The Pollino range is a region of slow deformation where earthquakes generally nucleate on low-angle normal faults. Recent studies have mapped fault structures and identified fluid related dynamics responsible for historical and recent seismicity in the area. Here, we apply the coda-normalization method at multiple frequencies and scales to image the 3-D P-wave attenuation (QP) properties of its slowly deforming fault network. The wide-scale average attenuation properties of the Pollino range are typical for a stable continental block, with a dependence of QP on frequency of Q−1 P = (0.0011   0.0008) f (0.36 0.32). Using only waveforms comprised in the area of seismic swarms, the dependence of attenuation on frequency increases [Q−1 P = (0.0373   0.0011) f (−0.59 0.01)], as expected when targeting seismically active faults. A shallow very-low-attenuation anomaly (max depth of 4–5 km) caps the seismicity recorded within the western cluster 1 of the Pollino seismic sequence (2012, maximum magnitude Mw = 5.1). High-attenuation volumes below this anomaly are likely related to fluid storage and comprise the western and northern portions of cluster 1 and the Mercure basin. These anomalies are constrained to the NW by a sharp low-attenuation interface, corresponding to the transition towards the eastern unit of the Apennine Platform under the Lauria mountains. The low-seismicity volume between cluster 1 and cluster 2 (maximum magnitude Mw = 4.3, east of the primary) shows diffuse low-to-average attenuation features. There is no clear indication of fluid-filled pathways between the two clusters resolvable at our resolution. In this volume, the attenuation values are anyway lower than in recognized low-attenuation blocks, like the Lauria Mountain and Pollino Range. As the volume develops in a region marked at surface by small-scale cross-faulting, it suggests no actual barrier between clusters, more likely a system of small locked fault patches that can break in the future. Our model loses resolution at depth, but it can still resolve a 5-to-15-km-deep high-attenuation anomaly that underlies the Castrovillari basin. This anomaly is an ideal deep source for the SE-to-NW migration of historical seismicity. Our novel deep structural maps support the hypothesis that the Pollino sequence has been caused by a mechanism of deep and lateral fluid-induced migration.
    Beschreibung: Natural Environment Research Council (NERC) Centre for Doctoral Training (CDT) in Oil and Gas. University of Aberdeen.
    Beschreibung: Published
    Beschreibung: 536–547
    Beschreibung: 4T. Sismicità dell'Italia
    Beschreibung: JCR Journal
    Schlagwort(e): body waves ; seismic attenuation ; seismic tomography ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 6
    Publikationsdatum: 2022-08-26
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©: The Authors 2022. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. Uploaded in accordance with the publisher's self-archiving policy.
    Beschreibung: Defining the regional variability of minimum magnitude for earthquake detection is crucial for planning seismic networks. Knowing the earthquake detection magnitude values is fundamental for the optimal location of new stations and to select the priority for reactivating the stations of a seismic network in case of a breakdown. In general, the assessment of earthquake detection is performed by analysing seismic noise with spectral or more sophisticated methods. Further, to simulate amplitude values at the recording sites, spectral methods require knowledge of several geophysical parameters including rock density, S-wave velocity, corner frequency, quality factor, site specific decay parameter and so on, as well as a velocity model for the Earth's interior. The simulation results are generally expressed in terms of Mw and therefore a further conversion must be done to obtain the values of local magnitude (ML), which is the parameter commonly used for moderate and small earthquakes in seismic catalogues. Here, the relationship utilized by a seismic network to determine ML is directly applied to obtain the expected amplitude [in mm, as if it were recorded by a Wood–Anderson (WA) seismometer] at the recording site, without any additional assumptions. The station detection estimates are obtained by simply considering the ratio of the expected amplitude with respect to the background noise, also measured in mm. The seismic noise level for the station is estimated starting from four waveforms (each signal lasting 1 min) sampled at various times of the day for a period of one week. The proposed method is tested on Italian seismic events occurring in 2019 by using the locations of 16.879 earthquakes recorded by 374 stations. The first results indicate that by evaluating the station noise level with 5-s windows, a representative sample of the variability in expected noise level is generated for every station, even if only 4 min of signal per day over a week of recordings is used. The method was applied to define the detection level of the Italian National Seismic Network (RSN). The RSN detection level represents a reference for the definition and application of guidelines in the field of monitoring of subsurface industrial activities in Italy. The proposed approach can be successfully applied to define the current performance of a local seismic network (managed by private companies) and to estimate the expected further improvements, requested to fulfil the guidelines with the installation of new seismic stations. This method has been tested in Italy and can be reproduced wherever the local magnitude ML, based on synthetic WA records, is used.
    Beschreibung: Published
    Beschreibung: 1283–1297
    Beschreibung: 4T. Sismicità dell'Italia
    Beschreibung: JCR Journal
    Schlagwort(e): Time-series analysis ; Earthquake ground motions ; Seismic noise ; Induced seismicity ; 04.06. Seismology ; 05.04. Instrumentation and techniques of general interest
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 7
    Publikationsdatum: 2021-03-15
    Beschreibung: In a recent work we computed the relative frequencies with which strong shocks (4.0≤Mw〈5.0), widely felt by the population were followed in the same area by potentially destructive main shocks (Mw≥5.0) in Italy. Assuming the stationarity of the seismic release properties, such frequencies can be tentatively used to estimate the probabilities of potentially destructive shocks after the occurrence of future strong shocks. This allows us to set up an alarm-based forecasting hypothesis related to strong foreshocks occurrence. Such hypothesis is tested retrospectively on the data of a homogenized seismic catalogue of the Italian area against a purely random hypothesis that simply forecasts the target main shocks proportionally to the space-time fraction occupied by the alarms. We compute the latter fraction in two ways a) as the ratio between the average time covered by the alarms in each area and the total duration of the forecasting experiment (60 years) and b) as the same ratio but weighted by the past frequency of occurrence of earthquakes in each area. In both cases the overall retrospective performance of our forecasting algorithm is definitely better than the random case. Considering an alarm duration of three months, the algorithm retrospectively forecasts more than 70% of all shocks with Mw5.5 occurred in Italy from 1960 to 2019 with a total space-time fraction covered by the alarms of the order of 2%. Considering the same space-time coverage, the algorithm is also able to retrospectively forecasts more than 40% of the first main shocks with Mw5.5 of the seismic sequences occurred in the same time interval. Given the good reliability of our results, the forecasting algorithm is set and ready to be tested also prospectively, in parallel to other ongoing procedures operating on the Italian territory.
    Beschreibung: This paper benefitted from funding provided by the European Union within the ambit of the H2020 project RISE (No. 821115), which in particular fully financed the PhD grant of one of the authors (E.B.).
    Beschreibung: Published
    Beschreibung: 1192–1206
    Beschreibung: 6T. Studi di pericolosità sismica e da maremoto
    Beschreibung: JCR Journal
    Schlagwort(e): Earthquake interaction ; Statistical seismology ; forecasting, ; prediction ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 8
    Publikationsdatum: 2021-03-24
    Beschreibung: The 2016–17 central Italy earthquake sequence began with the first mainshock near the town of Amatrice on August 24 (MW 6.0), and was followed by two subsequent large events near Visso on October 26 (MW 5.9) and Norcia on October 30 (MW 6.5), plus a cluster of 4 events with MW 〉 5.0 within few hours on January 18, 2017. The affected area had been monitored before the sequence started by the permanent Italian National Seismic Network (RSNC), and was enhanced during the sequence by temporary stations deployed by the National Institute of Geophysics and Volcanology and the British Geological Survey. By the middle of September, there was a dense network of 155 stations, with a mean separation in the epicentral area of 6–10 km, comparable to the most likely earthquake depth range in the region. This network configuration was kept stable for an entire year, producing 2.5 TB of continuous waveform recordings. Here we describe how this data was used to develop a large and comprehensive earthquake catalogue using the Complete Automatic Seismic Processor (CASP) procedure. This procedure detected more than 450,000 events in the year following the first mainshock, and determined their phase arrival times through an advanced picker engine (RSNI-Picker2), producing a set of about 7 million P- and 10 million S-wave arrival times. These were then used to locate the events using a non-linear location (NLL) algorithm, a 1D velocity model calibrated for the area, and station corrections and then to compute their local magnitudes (ML). The procedure was validated by comparison of the derived data for phase picks and earthquake parameters with a handpicked reference catalogue (hereinafter referred to as ‘RefCat’). The automated procedure takes less than 12 hours on an Intel Core-i7 workstation to analyse the primary waveform data and to detect and locate 3000 events on the most seismically active day of the sequence. This proves the concept that the CASP algorithm can provide effectively real-time data for input into daily operational earthquake forecasts, The results show that there have been significant improvements compared to RefCat obtained in the same period using manual phase picks. The number of detected and located events is higher (from 84,401 to 450,000), the magnitude of completeness is lower (from ML 1.4 to 0.6), and also the number of phase picks is greater with an average number of 72 picked arrival for a ML = 1.4 compared with 30 phases for RefCat using manual phase picking. These propagate into formal uncertainties of ± 0.9km in epicentral location and ± 1.5km in depth for the enhanced catalogue for the vast majority of the events. Together, these provide a significant improvement in the resolution of fine structures such as local planar structures and clusters, in particular the identification of shallow events occurring in parts of the crust previously thought to be inactive. The lower completeness magnitude provides a rich data set for development and testing of analysis techniques of seismic sequences evolution, including real-time, operational monitoring of b-value, time-dependent hazard evaluation and aftershock forecasting.
    Beschreibung: Published
    Beschreibung: 555–571
    Beschreibung: 3T. Fisica dei terremoti e Sorgente Sismica
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 9
    Publikationsdatum: 2021-05-12
    Beschreibung: erratum paper
    Beschreibung: Published
    Beschreibung: 1090-1092
    Beschreibung: 1T. Struttura della Terra
    Beschreibung: JCR Journal
    Schlagwort(e): Theoretical seismology ; Seismic attenuation ; Seismic noise ; Surface waves ; Free oscillations ; Seismic interferometry ; 04.06. Seismology ; 04.01. Earth Interior
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 10
    Publikationsdatum: 2021-06-14
    Beschreibung: Southwestern Sicily is an area of infrequent seismic activity; however, some studies carried out in the archaeological Selinunte site suggest that, between the fourth century BC and the early Middle Ages, probably at least two earthquakes strucked this area with enough energy to damage and cause the collapse and kinematics of much of the architecture of Selinunte. Take into account that, in 2008, a noninvasive archaeological prospection and traditional data gathering methods along the Acropolis north fortifications were carried out. Following these first studies, after about 10 years, a new geophysical campaign was carried out. This second campaign benefited from the application of modern technologies for the acquisition and processing of the point cloud data on the northern part of the Acropolis, like terrestrial laser scanning and unmanned aerial vehicle photogrammetry. In this paper, we present the application of these techniques and a strategy for their integration for the 3D modelling of buildings and cultural heritages. We show how the integration of data acquired independently by these two techniques is an added value able to overcome the intrinsic limits of the individual techniques. The application to Selinunte's Acropolis allowed it to highlight and measure with high accuracy fractures, dislocation, inclinations of walls, depressions of some areas and other interesting observations, which may be important starting points for future investigations.
    Beschreibung: Published
    Beschreibung: 153-165
    Beschreibung: 2IT. Laboratori analitici e sperimentali
    Beschreibung: JCR Journal
    Schlagwort(e): 3D reconstruction ; archaeological survey ; digital elevation model ; Selinunte Archaeological Park ; terrestrial laser scanning ; unmanned aerial vehicle photogrammetry ; 05.04. Instrumentation and techniques of general interest ; 04.02. Exploration geophysics ; 05.02. Data dissemination ; 05.06. Methods
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 11
    Publikationsdatum: 2021-04-14
    Beschreibung: The scaling of earthquake parameters with seismic moment and its interpretation in terms of self- similarity is still debated in the literature. We address this question by examining a worldwide compilation of corner frequency-based and elastic rebound theory (ERT)-based fault slip, area and stress drop values for earthquakes ranging in magnitude from -0.7 to 7.8. We find that corner frequency estimates of slip (and stress drop) scale differently than those inferred from the ERT approach, where the latter deviates from the generally accepted constant stress drop behavior of so- called self-similar scaling models. We also find that average slips from finite-source models are consistent with corner frequency scaling, whereas peak slip values are more consistent with the ERT scaling. The different scaling of corner frequency- and ERT-based estimates of slip and stress drop with earthquake size is interpreted in terms of heterogeneity of the rupture process. ERT-based estimates of stress drop decrease with seismic moment suggesting a self-affine behavior. Despite the inferred heterogeneity at all scales, we do not observe a clear effect on the Brune stress drop scaling with earthquake size.
    Beschreibung: Published
    Beschreibung: 1771–1781
    Beschreibung: 2T. Deformazione crostale attiva
    Beschreibung: JCR Journal
    Schlagwort(e): Earthquake dynamics ; Earthquake source observations ; Dynamics and mechanics of faulting ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 12
    Publikationsdatum: 2021-05-12
    Beschreibung: We have constructed a 3-D shear wave velocity (Vs) model for the crust and uppermost mantle beneath the Middle East using Rayleigh wave records obtained from ambient-noise cross-correlations and regional earthquakes. We combined one decade of data collected from 852 permanent and temporary broad-band stations in the region to calculate group-velocity dispersion curves. A compilation of 〉54 000 ray paths provides reliable group-velocity measurements for periods between 2 and 150 s. Path-averaged group velocities calculated at different periods were inverted for 2-D group-velocity maps. To overcome the problem of heterogeneous ray coverage, we used an adaptive grid parametrization for the group-velocity tomographic inversion. We then sample the period-dependent group-velocity field at each cell of a predefined grid to generate 1-D group-velocity dispersion curves, which are subsequently inverted for 1-D Vs models beneath each cell and combined to approximate the 3-D Vs structure of the area. The Vs model shows low velocities at shallow depths (5–10 km) beneath the Mesopotamian foredeep, South Caspian Basin, eastern Mediterranean and the Black Sea, in coincidence with deep sedimentary basins. Shallow high-velocity anomalies are observed in regions such as the Arabian Shield, Anatolian Plateau and Central Iran, which are dominated by widespread magmatic exposures. In the 10–20 km depth range, we find evidence for a band of high velocities (〉4.0 km s–1) along the southern Red Sea and Arabian Shield, indicating the presence of upper mantle rocks. Our 3-D velocity model exhibits high velocities in the depth range of 30–50 km beneath western Arabia, eastern Mediterranean, Central Iranian Block, South Caspian Basin and the Black Sea, possibly indicating a relatively thin crust. In contrast, the Zagros mountain range, the Sanandaj-Sirjan metamorphic zone in western central Iran, the easternmost Anatolian plateau and Lesser Caucasus are characterized by low velocities at these depths. Some of these anomalies may be related to thick crustal roots that support the high topography of these regions. In the upper mantle depth range, high-velocity anomalies are obtained beneath the Arabian Platform, southern Zagros, Persian Gulf and the eastern Mediterranean, in contrast to low velocities beneath the Red Sea, Arabian Shield, Afar depression, eastern Turkey and Lut Block in eastern Iran. Our Vs model may be used as a new reference crustal model for the Middle East in a broad range of future studies.
    Beschreibung: Published
    Beschreibung: 1349-1365
    Beschreibung: 1T. Struttura della Terra
    Beschreibung: JCR Journal
    Schlagwort(e): 04.01. Earth Interior ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 13
    Publikationsdatum: 2022-03-25
    Beschreibung: Campi Flegrei caldera (Southern Italy) is one of the most hazardous volcanic complexes in the world since it is located inside the densely inhabited urban district of Naples-Pozzuoli. In the past, the caldera has produced devastating to moderate eruptions and periodically undergoes from strong to minor uplift episodes, named “bradyseism”, almost always accompanied by seismic swarms. Starting from 2005 Campi Flegrei has undergone an unrest crisis, characterized by ground uplift, localized gas emissions and seismicity, often occurring in seismic swarms. As a consequence, the monitoring activities have been progressively increasing, producing a huge amount of data, difficult to manage and match. GIS (Geographical Information System) represents a potent tool to manage great quantity of data, coming from different disciplines. In this study, we show two GIS technology applications to the seismic catalogue of Campi Flegrei. In the first one, a high-quality dataset is extracted from the GeoDatabase addressed to seismological studies that require high precision earthquake locations. In the second application, GIS are used to extract, visualize and analyse the typical seismic swarms of Campi Flegrei. Moreover, density and seismic moment distribution maps were generated for these swarms. In the last application, the GIS allow to highlight a clear variation in the temporal trend of the seismic swarms at Campi Flegrei.
    Beschreibung: This study has benefited from funding provided by the Italian Presidenza del Consiglio dei Ministri – Dipartimento della Protezione Civile.
    Beschreibung: Published
    Beschreibung: 131-144
    Beschreibung: 4V. Processi pre-eruttivi
    Beschreibung: 6SR VULCANI – Servizi e ricerca per la società
    Beschreibung: 1IT. Reti di monitoraggio e sorveglianza
    Beschreibung: N/A or not JCR
    Schlagwort(e): Campi Flegrei ; Seismic swams ; Seismic network ; GIS ; 04.06. Seismology ; 04.08. Volcanology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 14
    Publikationsdatum: 2021-12-24
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©: The Authors 2021. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. Uploaded in accordance with the publisher's self-archiving policy.
    Beschreibung: Ambient-noise records from the AlpArray network are used to measure Rayleigh wave phase velocities between more than 150,000 station pairs. From these, azimuthally anisotropic phase-velocity maps are obtained by applying the Eikonal tomography method. Several synthetic tests are shown to study the bias in the Ψ2 anisotropy. There are two main groups of bias, the first one caused by interference between refracted/reflected waves and the appearance of secondary wavefronts that affect the phase travel-time measurements. This bias can be reduced if the amplitude field can be estimated correctly. Another source of error is related to the incomplete reconstruction of the travel-time field that is only sparsely sampled due to the receiver locations. Both types of bias scale with the magnitude of the velocity heterogeneities. Most affected by the spurious Ψ2 anisotropy are areas inside and at the border of low-velocity zones. In the isotropic velocity distribution, most of the bias cancels out if the azimuthal coverage is good. Despite the lack of resolution in many parts of the surveyed area, we identify a number of anisotropic structures that are robust: in the central Alps, we find a layered anisotropic structure, arc-parallel at midcrustal depths and arc-perpendicular in the lower crust. In contrast, in the eastern Alps, the pattern is more consistently E-W oriented which we relate to the eastward extrusion. The northern Alpine forleand exhibits a preferential anisotropic orientation that is similar to SKS observations in the lowermost crust and uppermost mantle.
    Beschreibung: German Science Foundation (SPP-2017, Project Ha 2403/21-1); Swiss National Science Foundation SINERGIA Project CRSII2-154434/1 (Swiss-AlpArray); Progetto Pianeta Dinamico, finanziamento MUR-INGV, Task S2 – 2021
    Beschreibung: Published
    Beschreibung: 151–170
    Beschreibung: 1T. Struttura della Terra
    Beschreibung: JCR Journal
    Schlagwort(e): Seismic anisotropy ; Seismic interferometry ; Seismic tomography ; Wave propagation ; Continental tectonics: compressional ; 04.01. Earth Interior ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 15
    Publikationsdatum: 2021-12-15
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©: The Authors 2022. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. Uploaded in accordance with the publisher's self-archiving policy.
    Beschreibung: To understand the seismotectonics and the seismic hazard of the study sector of the Northern Apennines (Italy), one of the most important earthquakes of magnitude Mw = 6.5 which struck the Lunigiana and Garfagnana areas (Tuscany) on 7 September 1920 should be studied. Given the early instrumental epoch of the event, neither geometric and kinematic information on the fault-source nor its fault-plane solution were available. Both areas were candidates for hosting the source fault and there was uncertainty between a normal fault with Apenninic direction or an anti-Apenninic strike-slip. We retrieved 11 focal parameters (including the fault-plane solution) of the 1920 earthquake. Only macroseismic intensity information (from 499 inhabited centres) through the KF-NGA inversion technique was used. This technique uses a Kinematic model of the earthquake source and speeds up the calculation by a Genetic Algorithm with Niching. The result is a pure dip-slip focal solution. The intrinsic ambiguities of the KF-NGA method (±180° on the rake angle; choice of the fault plane between the two nodal planes) were solved with field and seismotectonic evidence. The earthquake was generated by a normal fault (rake angle = 265° ± 8°) with an Apennine direction (114° ± 5°) and dipping 38° ± 6° towards SW. The likely candidate for hosting the source-fault in 1920 is the Compione-Comano fault that borders the NE edge of the Lunigiana graben. The KF-NGA algorithm proved to be invaluable for studying the kinematics of early instrumental earthquakes and allowed us to uniquely individuate, for the first time ever, the seismogenic source of the 1920 earthquake. Our findings have implications in hazard computation and seismotectonic contexts.
    Beschreibung: Published
    Beschreibung: 1465–1477
    Beschreibung: 4T. Sismicità dell'Italia
    Beschreibung: JCR Journal
    Schlagwort(e): Inverse theory ; Body waves ; Earthquake source observations ; Seismicity and tectonics ; Dynamics: seismotectonics ; Fractures, faults, and high strain deformation zones ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 16
    Publikationsdatum: 2023-11-21
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved.
    Beschreibung: On 24 August 2016 at 01:36 UTC a ML6.0 earthquake struck several villages in central Italy, among which Accumoli, Amatrice and Arquata del Tronto. The earthquake was recorded by about 350 seismic stations, causing 299 fatalities and damage with macroseismic intensities up to 11. The maximum acceleration was observed at Amatrice station (AMT) reaching 916 cm s–2 on E–W component, with epicentral distance of 15 km and Joyner and Boore distance to the fault surface (RJB) of less than a kilometre. Motivated by the high levels of observed ground motion and damage, we generate broad-band seismograms for engineering purposes by adopting a hybrid method. To infer the low frequency seismograms, we considered the kinematic slip model by Tinti et al . The high frequency seismograms were produced using a stochastic finite-fault model approach based on dynamic corner-frequency. Broadband synthetic time-series were therefore obtained by merging the low and high frequency seismograms. Simulated hybrid ground motions were compared both with the observed ground motions and the ground-motion prediction equations (GMPEs), to explore their performance and to retrieve the region-specific parameters endorsed for the simulations. In the near-fault area we observed that hybrid simulations have a higher capability to detect near source effects and to reproduce the source complexity than the use of GMPEs. Indeed, the general good consistency found between synthetic and observed ground motion (both in the time and frequency domain), suggests that the use of regional-specific source scaling and attenuation parameters together with the source complexity in hybrid simulations improves ground motion estimations. To include the site effect in stochastic simulations at selected stations, we tested the use of amplification curves derived from HVRSs (horizontal-to-vertical response spectra) and from HVSRs (horizontal-to-vertical spectral ratios) rather than the use of generic curves according to NTC18 Italian seismic design code. We generally found a further reduction of residuals between observed and simulated both in terms of time histories and spectra.
    Beschreibung: Published
    Beschreibung: 1753–1779
    Beschreibung: 6T. Studi di pericolosità sismica e da maremoto
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 17
    Publikationsdatum: 2023-11-16
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2020. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved
    Beschreibung: This study describes a deep convolutional neural network (CNN) based technique for the prediction of intensity measurements (IMs) of ground shaking. The input data to the CNN model consists of multistation 3C broadband and accelerometric waveforms recorded during the 2016 Central Italy earthquake sequence for M $\ge$ 3.0. We find that the CNN is capable of predicting accurately the IMs at stations far from the epicenter and that have not yet recorded the maximum ground shaking when using a 10 s window starting at the earthquake origin time. The CNN IM predictions do not require previous knowledge of the earthquake source (location and magnitude). Comparison between the CNN model predictions and the predictions obtained with Bindi et al. (2011) GMPE (which require location and magnitude) has shown that the CNN model features similar error variance but smaller bias. Although the technique is not strictly designed for earthquake early warning, we found that it can provide useful estimates of ground motions within 15-20 sec after earthquake origin time depending on various setup elements (e.g., times for data transmission, computation, latencies). The technique has been tested on raw data without any initial data pre-selection in order to closely replicate real-time data streaming. When noise examples were included with the earthquake data, the CNN was found to be stable predicting accurately the ground shaking intensity corresponding to the noise amplitude.
    Beschreibung: Published
    Beschreibung: 1379–1389
    Beschreibung: 8T. Sismologia in tempo reale
    Beschreibung: JCR Journal
    Schlagwort(e): Physics - Geophysics; Physics - Geophysics ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 18
    Publikationsdatum: 2023-11-16
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2020. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved.
    Beschreibung: In volcanoes, topography, shallow heterogeneity and even shallow morphology can substan- tially modify seismic coda signals. Coda waves are an essential tool to monitor eruption dynamics and model volcanic structures jointly and independently from velocity anomalies: it is thus fundamental to test their spatial sensitivity to seismic path effects. Here, we apply the Multiple Lapse Time Window Analysis (MLTWA) to measure the relative importance of scattering attenuation vs absorption at Mount St Helens volcano before its 2004 erup- tion. The results show the characteristic dominance of scattering attenuation in volcanoes at lower frequencies (3–6 Hz), while absorption is the primary attenuation mechanism at 12 and 18 Hz. Scattering attenuation is similar but seismic absorption is one order of magnitude lower than at open-conduit volcanoes, like Etna and Kilauea, a typical behaviour of a (rela- tively) cool magmatic plumbing system. Still, the seismic albedo (measuring the ratio between seismic energy emitted and received from the area) is anomalously high (0.95) at 3 Hz. A radiative-transfer forward model of far- and near-field envelopes confirms this is due to strong near-receiver scattering enhancing anomalous phases in the intermediate and late coda across the 1980 debris avalanche and central crater. Only above this frequency and in the far-field diffusion onsets at late lapse times. The scattering and absorption parameters derived from MLTWA are used as inputs to construct 2-D frequency-dependent bulk sensitivity kernels for the S-wave coda in the multiple-scattering (using the Energy Transport Equations—ETE) and diffusive (AD, independent of MLTWA results) regimes. At 12 Hz, high coda-attenuation anomalies characterize the eastern side of the volcano using both kernels, in spatial correla- tion with low-velocity anomalies from literature. At 3 Hz, the anomalous albedo, the forward modelling, and the results of the tomographic imaging confirm that shallow heterogeneity beneath the extended 1980 debris-avalanche and crater enhance anomalous intermediate and late coda phases, mapping shallow geological contrasts. We remark the effect this may have on coda-dependent source inversion and tomography, currently used across the world to image and monitor volcanoes. At Mount St Helens, higher frequencies and deep borehole data are necessary to reconstruct deep volcanic structures with coda waves.
    Beschreibung: Scottish Alliance for Geosciences Environment and Society and the Kleinman Grant for Volcano Research
    Beschreibung: Published
    Beschreibung: 169-188
    Beschreibung: 1T. Struttura della Terra
    Beschreibung: 2V. Struttura e sistema di alimentazione dei vulcani
    Beschreibung: 3IT. Calcolo scientifico
    Beschreibung: JCR Journal
    Schlagwort(e): NorthAmerica ; Wave scattering and diffraction. ; Codawaves ; Seismicattenuation ; Seismic tomography ; Volcano seismology ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 19
    Publikationsdatum: 2023-11-14
    Beschreibung: This article has been accepted for publication in Geophysical Journal International ©:The Author(s) 2020. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Uploaded in accordance with the publisher's self-archiving policy. All rights reserved.
    Beschreibung: We compile a data set of Rayleigh-wave phase velocities between pairs of stations, based on teleseismic events located on the same great circle as the two stations. We validate our observations against dispersion estimates based on ambient-noise cross correlations at the same station pairs. Discrepancies between the results of the two methods can in principle be explained by deviations in the wave propagation path between earthquake and receivers, due to lateral heterogeneity in the Earth’s structure, but the latter effect has, so far, not been precisely quantified nor corrected for. We implement an algorithm to measure the arrival angle of earthquake-generated surface waves and correct the dispersion measurements accordingly. Application to a data set from the Central-Western Mediterranean shows that the arrival-angle correction almost entirely accounts for the discrepancy in question, decreasing significantly the velocity bias for a wide range of periods.
    Beschreibung: Published
    Beschreibung: 1838–1844
    Beschreibung: 1T. Struttura della Terra
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 20
    Publikationsdatum: 2020-01-31
    Beschreibung: Within the framework of the European collaborative research initiative AlpArray (http://www.alparray.ethz. ch), the Istituto Nazionale di Geofisica e Vulcanolgia (INGV) deployed overall 20 broad-band seismic stations in Northern Italy and on two islands in the Tyrrhenian Sea (Capraia and Montecristo) during Fall-Winter 2015. The temporary deployment (16 stations) will run for two to three years and 4 INGV National Seismic Network accelerometric sites are now equipped with additional per- manent broad-band sensors. The 16 temporary stations are equipped with REF TEK 130 digitizers and Nanometrics Trillium Compact 120 s sensors, a couple have Nanometrics Trillium 120P sensors and one a Streckeisen STS2. For each site we describe the settings and discuss the noise levels, the site effects and the preliminary sensitivity analysis.
    Beschreibung: Published
    Beschreibung: 39-52
    Beschreibung: 8T. Sismologia in tempo reale
    Beschreibung: JCR Journal
    Schlagwort(e): 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 21
    Publikationsdatum: 2020-05-25
    Beschreibung: We explore the three‐dimensional structure of the 2016–2017 Central Italy sequence using ~34,000 ML ≥ 1.5 earthquakes that occurred between August 2016 and January 2018. We applied cross‐correlation and double‐difference location methods to waveform and parametric data routinely produced at the Italian National Institute of Geophysics and Volcanology. The sequence activated an 80 km long system of normal faults and near‐horizontal detachment faults through the MW 6.0 Amatrice, the MW 5.9 Visso, and the MW 6.5 Norcia mainshocks and aftershocks. The system has an average strike of N155°E and dips 38°–55° southwestward and is segmented into 15–30 km long faults individually activated by the cascade of MW ≥ 5.0 shocks. The two main normal fault segments, Mt. Vettore‐Mt. Bove to the North and Mt. della Laga to the South, are separated by an NNE‐SSW‐trending lateral ramp of the Sibillini thrust, a regional structure inherited from the previous compressional tectonic phase putting into contact diverse lithologies with different seismicity patterns. Space‐time reconstruction of the fault system supports a composite rupture scenario previously proposed for the MW 6.5 Norcia earthquake, where the rupture possibly propagated also along an oblique portion of the Sibillini thrust. This dissected set of normal fault segments is bounded at 8–10 km depth by a continuous 2 km thick seismicity layer of extensional nature slightly dipping eastward and interpreted as a shear zone. All three mainshocks in the sequence nucleated along the high‐angle planes at significant distance from the shear zone, thus complicating the interpretation of the mechanisms driving strain partitioning between these structures.
    Beschreibung: Published
    Beschreibung: e2019JB018440
    Beschreibung: 3T. Sorgente sismica
    Beschreibung: JCR Journal
    Schlagwort(e): normal fault ; shear zone ; fault segmentation ; apennines ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 22
    Publikationsdatum: 2020-07-08
    Beschreibung: The response of continental forelands to subduction and collision is a widely investigated topic in geodynamics. The deformation occurring within a foreland shared by two opposite‐verging chains, however, is uncommon and poorly understood. The Apulia Swell in the southern end of the Adria microplate (Africa‐Europe plate boundary, central Mediterranean Sea) represents one of these cases, as it is the common foreland of the SW verging Albanides‐Hellenides and the NE verging Southern Apennines merging into the SSE verging Calabrian Arc. We investigated the internal deformation of the Apulia Swell using multiscale geophysical data: multichannel seismic profiles recording up to 12‐s two‐way time (TWT) for a consistent image of the upper crust; high‐resolution multichannel seismic profiles, high‐resolution multibeam bathymetry, and CHIRP profiles acquired by R/V OGS Explora to constrain the Quaternary geological record. The results of our analyses characterize the geometry of the South Apulia Fault System (SAFS), a 100‐km‐long and 12‐km‐wide structure attesting an extensional (and possibly transtensional) response of the foreland to the two contractional fronts. The SAFS consists of two NW‐SE right‐stepping master faults and several secondary structures. The SAFS activity spans from the Early Pleistocene through the Holocene, as testified by the bathymetric and high‐resolution seismic data, with long‐term slip rates in the range of 0.2–0.4 mm/yr. Considering the position within an area with few or none other active faults in the surroundings, the dimension, and the activity rates, the SAFS can be a candidate causative fault of the 20 February 1743, M 6.7, earthquake.
    Beschreibung: Italian Ministry for Education, University, and Research (MIUR), Premiale 2014 D. M. 291 03/05/2016.
    Beschreibung: Published
    Beschreibung: e2020TC006116
    Beschreibung: 2T. Deformazione crostale attiva
    Beschreibung: 2TR. Ricostruzione e modellazione della struttura crostale
    Beschreibung: JCR Journal
    Schlagwort(e): active tectonics ; apulia ; south apulia fault system ; 1743 earthquake ; marine geology ; stable continental region ; ionian sea ; active faults ; subsurface geology ; seismic interpretation ; 04.04. Geology ; 04.07. Tectonophysics ; 04.02. Exploration geophysics
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 23
    Publikationsdatum: 2020-04-09
    Beschreibung: This work is devoted to the study of both earthquakes and background seismic noise at Ischia Island (Italy) recorded pre and post the Md 4.0 earthquake occurred on 21 August 2017 (18:57 UTC). We compare and characterize noise and earthquakes in terms of Independent Component Analysis, energy and polarization properties. The earthquakes’ waveforms and the background noise are decomposed into a few independent components with two main common signals peaked around 1–2 and 3–4 Hz, respectively. A slight increase of the energy of the background seismic noise is observed comparing samples recorded in 2016 and 2017, whereas no variations are detected in 2017 pre and post the main earthquake. The polarization analysis, performed in the frequency bands individuated by Independent Component Analysis and applied to the background seismic noise, indicates a shallow propagation and the azimuthal pattern is mainly controlled by the local structural features. These results suggest that noise and earthquakes are ascribable to a common phenomenon of fluid-solid interaction in the hydrothermal system of Ischia Island.
    Beschreibung: Published
    Beschreibung: 19-28
    Beschreibung: 3T. Sorgente sismica
    Beschreibung: 4V. Processi pre-eruttivi
    Beschreibung: JCR Journal
    Schlagwort(e): Ischia volcano ; Source dynamics ; Data analysis ; 04.08. Volcanology ; 04.06. Seismology
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 24
    Publikationsdatum: 2017-01-10
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 25
    Publikationsdatum: 2017-01-10
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 26
    Publikationsdatum: 2016-06-21
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 27
    Publikationsdatum: 2016-06-21
    Beschreibung: 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 .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 28
    Publikationsdatum: 2016-06-21
    Beschreibung: 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 .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 29
    Publikationsdatum: 2016-06-21
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 30
    Publikationsdatum: 2016-05-06
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 31
    Publikationsdatum: 2016-05-06
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 32
    Publikationsdatum: 2016-07-09
    Beschreibung: 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 .
    Schlagwort(e): Computational Methods, Genomics
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  • 33
    Publikationsdatum: 2016-07-09
    Beschreibung: 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/.
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  • 34
    facet.materialart.
    Unbekannt
    Oxford University Press
    Publikationsdatum: 2016-07-09
    Beschreibung: 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 .
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  • 35
    Publikationsdatum: 2016-06-03
    Beschreibung: 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.
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  • 36
    Publikationsdatum: 2016-06-03
    Beschreibung: 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/ .
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  • 37
    Publikationsdatum: 2016-06-03
    Beschreibung: 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.
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  • 38
    Publikationsdatum: 2016-09-20
    Beschreibung: 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.
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  • 39
    Publikationsdatum: 2016-09-03
    Beschreibung: 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.
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  • 40
    Publikationsdatum: 2016-08-20
    Beschreibung: 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.
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  • 41
    Publikationsdatum: 2016-01-30
    Beschreibung: 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/ .
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  • 42
    Publikationsdatum: 2016-01-30
    Beschreibung: 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.
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  • 43
    Publikationsdatum: 2016-03-01
    Beschreibung: 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 ).
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  • 44
    Publikationsdatum: 2016-05-20
    Beschreibung: 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.
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  • 45
    Publikationsdatum: 2016-05-20
    Beschreibung: 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/ .
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  • 46
    Publikationsdatum: 2016-05-20
    Beschreibung: 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.
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  • 47
    Publikationsdatum: 2016-05-20
    Beschreibung: 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.
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  • 48
    Publikationsdatum: 2016-04-08
    Beschreibung: 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.
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  • 49
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 50
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 51
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 52
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 53
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 54
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
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  • 55
    Publikationsdatum: 2016-03-19
    Beschreibung: 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.
    Schlagwort(e): Computational Methods, Genomics
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  • 56
    Publikationsdatum: 2016-05-06
    Beschreibung: An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.
    Schlagwort(e): Computational Methods, Genomics
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  • 57
    Publikationsdatum: 2016-04-08
    Beschreibung: Small non-coding RNAs play a key role in many physiological and pathological processes. Since 2004, miRNA sequences have been catalogued in miRBase, which is currently in its 21st version. We investigated sequence and structural features of miRNAs annotated in the miRBase and compared them between different versions of this reference database. We have identified that the two most recent releases (v20 and v21) are influenced by next-generation sequencing based miRNA predictions and show significant deviation from miRNAs discovered prior to the high-throughput profiling period. From the analysis of miRBase, we derived a set of key characteristics to predict new miRNAs and applied the implemented algorithm to evaluate novel blood-borne miRNA candidates. We carried out 705 individual whole miRNA sequencings of blood cells and collected a total of 9.7 billion reads. Using miRDeep2 we initially predicted 1452 potentially novel miRNAs. After excluding false positives, 518 candidates remained. These novel candidates were ranked according to their distance to the features in the early miRBase versions allowing for an easier selection of a subset of putative miRNAs for validation. Selected candidates were successfully validated by qRT-PCR and northern blotting. In addition, we implemented a web-server for ranking potential miRNA candidates, which is available at: www.ccb.uni-saarland.de/novomirank .
    Schlagwort(e): Computational Methods, Genomics
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  • 58
    Publikationsdatum: 2016-04-21
    Beschreibung: The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.
    Schlagwort(e): Computational Methods, Genomics
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  • 59
    Publikationsdatum: 2016-04-21
    Beschreibung: The contribution of different mechanisms to the regulation of gene expression varies for different tissues and tumors. Complementation of predicted mRNA–miRNA and gene–transcription factor (TF) relationships with the results of expression correlation analyses derived for specific tumor types outlines the interactions with functional impact in the current biomaterial. We developed CrossHub software, which enables two-way identification of most possible TF–gene interactions: on the basis of ENCODE ChIP-Seq binding evidence or Jaspar prediction and co-expression according to the data of The Cancer Genome Atlas (TCGA) project, the largest cancer omics resource. Similarly, CrossHub identifies mRNA–miRNA pairs with predicted or validated binding sites (TargetScan, mirSVR, PicTar, DIANA microT, miRTarBase) and strong negative expression correlations. We observed partial consistency between ChIP-Seq or miRNA target predictions and gene–TF/miRNA co-expression, demonstrating a link between these indicators. Additionally, CrossHub expression-methylation correlation analysis can be used to identify hypermethylated CpG sites or regions with the greatest potential impact on gene expression. Thus, CrossHub is capable of outlining molecular portraits of a specific gene and determining the three most common sources of expression regulation: promoter/enhancer methylation, miRNA interference and TF-mediated activation or repression. CrossHub generates formatted Excel workbooks with the detailed results. CrossHub is freely available at https://sourceforge.net/projects/crosshub/ .
    Schlagwort(e): Computational Methods, Genomics
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  • 60
    Publikationsdatum: 2016-08-20
    Beschreibung: Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR (Ensemble Cell Lineage Analysis with Improved Robustness), a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
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  • 61
    Publikationsdatum: 2016-09-20
    Beschreibung: The quantification of transcriptomic features is the basis of the analysis of RNA-seq data. We present an integrated alignment workflow and a simple counting-based approach to derive estimates for gene, exon and exon–exon junction expression. In contrast to previous counting-based approaches, EQP takes into account only reads whose alignment pattern agrees with the splicing pattern of the features of interest. This leads to improved gene expression estimates as well as to the generation of exon counts that allow disambiguating reads between overlapping exons. Unlike other methods that quantify skipped introns, EQP offers a novel way to compute junction counts based on the agreement of the read alignments with the exons on both sides of the junction, thus providing a uniformly derived set of counts. We evaluated the performance of EQP on both simulated and real Illumina RNA-seq data and compared it with other quantification tools. Our results suggest that EQP provides superior gene expression estimates and we illustrate the advantages of EQP's exon and junction counts. The provision of uniformly derived high-quality counts makes EQP an ideal quantification tool for differential expression and differential splicing studies. EQP is freely available for download at https://github.com/Novartis/EQP-cluster .
    Schlagwort(e): Computational Methods, Genomics
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  • 62
    Publikationsdatum: 2016-09-20
    Beschreibung: We describe Boiler, a new software tool for compressing and querying large collections of RNA-seq alignments. Boiler discards most per-read data, keeping only a genomic coverage vector plus a few empirical distributions summarizing the alignments. Since most per-read data is discarded, storage footprint is often much smaller than that achieved by other compression tools. Despite this, the most relevant per-read data can be recovered; we show that Boiler compression has only a slight negative impact on results given by downstream tools for isoform assembly and quantification. Boiler also allows the user to pose fast and useful queries without decompressing the entire file. Boiler is free open source software available from github.com/jpritt/boiler .
    Schlagwort(e): Computational Methods, Genomics
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  • 63
    Publikationsdatum: 2016-10-14
    Beschreibung: Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity than is captured by existing annotation. The pervasive nature of overlapping transcription throughout herpesvirus genomes, however, poses substantial problems in resolving transcript structures using these methods alone. We present an approach that combines the unique attributes of Pacific Biosciences Iso-Seq long-read, Illumina short-read and deepCAGE (Cap Analysis of Gene Expression) sequencing to globally resolve polyadenylated isoform structures in replicating Epstein-Barr virus (EBV). Our method, Transcriptome Resolution through Integration of Multi-platform Data (TRIMD), identifies nearly 300 novel EBV transcripts, quadrupling the size of the annotated viral transcriptome. These findings illustrate an array of mechanisms through which EBV achieves functional diversity in its relatively small, compact genome including programmed alternative splicing (e.g. across the IR1 repeats), alternative promoter usage by LMP2 and other latency-associated transcripts, intergenic splicing at the BZLF2 locus, and antisense transcription and pervasive readthrough transcription throughout the genome.
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  • 64
    Publikationsdatum: 2016-10-14
    Beschreibung: Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiE, 3'E and Ed, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings.
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  • 65
    Publikationsdatum: 2016-12-01
    Beschreibung: Module identification is a frequently used approach for mining local structures with more significance in global networks. Recently, a wide variety of bilayer networks are emerging to characterize the more complex biological processes. In the light of special topological properties of bilayer networks and the accompanying challenges, there is yet no effective method aiming at bilayer module identification to probe the modular organizations from the more inspiring bilayer networks. To this end, we proposed the pseudo-3D clustering algorithm, which starts from extracting initial non-hierarchically organized modules and then iteratively deciphers the hierarchical organization of modules according to a bottom-up strategy. Specifically, a modularity function for bilayer modules was proposed to facilitate the algorithm reporting the optimal partition that gives the most accurate characterization of the bilayer network. Simulation studies demonstrated its robustness and outperformance against alternative competing methods. Specific applications to both the soybean and human miRNA-gene bilayer networks demonstrated that the pseudo-3D clustering algorithm successfully identified the overlapping, hierarchically organized and highly cohesive bilayer modules. The analyses on topology, functional and human disease enrichment and the bilayer subnetwork involved in soybean fat biosynthesis provided both the theoretical and biological evidence supporting the effectiveness and robustness of pseudo-3D clustering algorithm.
    Schlagwort(e): Computational Methods, Genomics
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  • 66
    Publikationsdatum: 2016-12-01
    Beschreibung: Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA-Seq data. The computational analysis is carried out on a laptop computer in 〈40 min.
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  • 67
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    Oxford University Press
    Publikationsdatum: 2016-01-09
    Beschreibung: De-novo motif search is a frequently applied bioinformatics procedure to identify and prioritize recurrent elements in sequences sets for biological investigation, such as the ones derived from high-throughput differential expression experiments. Several algorithms have been developed to perform motif search, employing widely different approaches and often giving divergent results. In order to maximize the power of these investigations and ultimately be able to draft solid biological hypotheses, there is the need for applying multiple tools on the same sequences and merge the obtained results. However, motif reporting formats and statistical evaluation methods currently make such an integration task difficult to perform and mostly restricted to specific scenarios. We thus introduce here the Dynamic Motif Integration Toolkit (DynaMIT), an extremely flexible platform allowing to identify motifs employing multiple algorithms, integrate them by means of a user-selected strategy and visualize results in several ways; furthermore, the platform is user-extendible in all its aspects. DynaMIT is freely available at http://cibioltg.bitbucket.org .
    Schlagwort(e): Computational Methods, Genomics
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  • 68
    Publikationsdatum: 2016-01-09
    Beschreibung: The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ~11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts.
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  • 69
    Publikationsdatum: 2016-01-09
    Beschreibung: DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction .
    Schlagwort(e): Computational Methods, Genomics
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  • 70
    Publikationsdatum: 2016-12-01
    Beschreibung: The advanced medium-throughput NanoString nCounter technology has been increasingly used for mRNA or miRNA differential expression (DE) studies due to its advantages including direct measurement of molecule expression levels without amplification, digital readout and superior applicability to formalin fixed paraffin embedded samples. However, the analysis of nCounter data is hampered because most methods developed are based on t-tests, which do not fit the count data generated by the NanoString nCounter system. Furthermore, data normalization procedures of current methods are either not suitable for counts or not specific for NanoString nCounter data. We develop a novel DE detection method based on NanoString nCounter data. The method, named NanoStringDiff, considers a generalized linear model of the negative binomial family to characterize count data and allows for multifactor design. Data normalization is incorporated in the model framework through data normalization parameters, which are estimated from positive controls, negative controls and housekeeping genes embedded in the nCounter system. We propose an empirical Bayes shrinkage approach to estimate the dispersion parameter in the model and a likelihood ratio test to identify differentially expressed genes. Simulations and real data analysis demonstrate that the proposed method performs better than existing methods.
    Schlagwort(e): Computational Methods, Genomics
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  • 71
    Publikationsdatum: 2016-12-17
    Beschreibung: We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching normal and tumor exomes and transcriptomes from 90 breast cancer patients from TCGA. Under high-confidence settings, RNA2DNAlign identified 2038 distinct SNV sites associated with one of the aforementioned asymetries, the majority of which have not been linked to functionality before. The performance assessment shows very high specificity and sensitivity, due to the corroboration of signals across multiple matching datasets. RNA2DNAlign is freely available from http://github.com/HorvathLab/NGS as a self-contained binary package for 64-bit Linux systems.
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  • 72
    Publikationsdatum: 2016-10-08
    Beschreibung: Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions.
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  • 73
    Publikationsdatum: 2015-09-19
    Beschreibung: Recent releases of genome three-dimensional (3D) structures have the potential to transform our understanding of genomes. Nonetheless, the storage technology and visualization tools need to evolve to offer to the scientific community fast and convenient access to these data. We introduce simultaneously a database system to store and query 3D genomic data ( 3DBG ), and a 3D genome browser to visualize and explore 3D genome structures ( 3DGB ). We benchmark 3DBG against state-of-the-art systems and demonstrate that it is faster than previous solutions, and importantly gracefully scales with the size of data. We also illustrate the usefulness of our 3D genome Web browser to explore human genome structures. The 3D genome browser is available at http://3dgb.cs.mcgill.ca/ .
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  • 74
    Publikationsdatum: 2015-05-29
    Beschreibung: Identification of transcription units (TUs) encoded in a bacterial genome is essential to elucidation of transcriptional regulation of the organism. To gain a detailed understanding of the dynamically composed TU structures, we have used four strand-specific RNA-seq (ssRNA-seq) datasets collected under two experimental conditions to derive the genomic TU organization of Clostridium thermocellum using a machine-learning approach. Our method accurately predicted the genomic boundaries of individual TUs based on two sets of parameters measuring the RNA-seq expression patterns across the genome: expression-level continuity and variance. A total of 2590 distinct TUs are predicted based on the four RNA-seq datasets. Among the predicted TUs, 44% have multiple genes. We assessed our prediction method on an independent set of RNA-seq data with longer reads. The evaluation confirmed the high quality of the predicted TUs. Functional enrichment analyses on a selected subset of the predicted TUs revealed interesting biology. To demonstrate the generality of the prediction method, we have also applied the method to RNA-seq data collected on Escherichia coli and achieved high prediction accuracies. The TU prediction program named SeqTU is publicly available at https://code.google.com/p/seqtu/ . We expect that the predicted TUs can serve as the baseline information for studying transcriptional and post-transcriptional regulation in C. thermocellum and other bacteria.
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  • 75
    Publikationsdatum: 2015-05-29
    Beschreibung: Detecting genetic variation is one of the main applications of high-throughput sequencing, but is still challenging wherever aligning short reads poses ambiguities. Current state-of-the-art variant calling approaches avoid such regions, arguing that it is necessary to sacrifice detection sensitivity to limit false discovery. We developed a method that links candidate variant positions within repetitive genomic regions into clusters. The technique relies on a resource, a thesaurus of genetic variation, that enumerates genomic regions with similar sequence. The resource is computationally intensive to generate, but once compiled can be applied efficiently to annotate and prioritize variants in repetitive regions. We show that thesaurus annotation can reduce the rate of false variant calls due to mappability by up to three orders of magnitude. We apply the technique to whole genome datasets and establish that called variants in low mappability regions annotated using the thesaurus can be experimentally validated. We then extend the analysis to a large panel of exomes to show that the annotation technique opens possibilities to study variation in hereto hidden and under-studied parts of the genome.
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  • 76
    Publikationsdatum: 2015-05-03
    Beschreibung: Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease.
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  • 77
    Publikationsdatum: 2015-05-03
    Beschreibung: The Metabolic Models Reconstruction Using Genome-Scale Information ( merlin ) tool is a user-friendly Java application that aids the reconstruction of genome-scale metabolic models for any organism that has its genome sequenced. It performs the major steps of the reconstruction process, including the functional genomic annotation of the whole genome and subsequent construction of the portfolio of reactions. Moreover, merlin includes tools for the identification and annotation of genes encoding transport proteins, generating the transport reactions for those carriers. It also performs the compartmentalisation of the model, predicting the organelle localisation of the proteins encoded in the genome and thus the localisation of the metabolites involved in the reactions promoted by such enzymes. The gene-proteins-reactions (GPR) associations are automatically generated and included in the model. Finally, merlin expedites the transition from genomic data to draft metabolic models reconstructions exported in the SBML standard format, allowing the user to have a preliminary view of the biochemical network, which can be manually curated within the environment provided by merlin .
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  • 78
    facet.materialart.
    Unbekannt
    Oxford University Press
    Publikationsdatum: 2015-05-03
    Beschreibung: For eukaryotic cells, the biological processes involving regulatory DNA elements play an important role in cell cycle. Understanding 3D spatial arrangements of chromosomes and revealing long-range chromatin interactions are critical to decipher these biological processes. In recent years, chromosome conformation capture (3C) related techniques have been developed to measure the interaction frequencies between long-range genome loci, which have provided a great opportunity to decode the 3D organization of the genome. In this paper, we develop a new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data. By modeling each chromosome as a polymer chain, we define the conformational energy based on our current knowledge on polymer physics and use it as prior information in the Bayesian framework. We also propose an expectation-maximization (EM) based algorithm to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data. We have validated our Bayesian inference approach through cross-validation and verified the computed chromatin conformations using the geometric constraints derived from fluorescence in situ hybridization (FISH) experiments. We have further confirmed the inferred chromatin structures using the known genetic interactions derived from other studies in the literature. Our test results have indicated that our Bayesian framework can compute an accurate ensemble of 3D chromatin conformations that best interpret the distance constraints derived from 3C-based data and also agree with other sources of geometric constraints derived from experimental evidence in the previous studies. The source code of our approach can be found in https://github.com/wangsy11/InfMod3DGen .
    Schlagwort(e): Computational Methods, Genomics
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  • 79
    Publikationsdatum: 2015-05-03
    Beschreibung: Characterization of cell type specific regulatory networks and elements is a major challenge in genomics, and emerging strategies frequently employ high-throughput genome-wide assays of transcription factor (TF) to DNA binding, histone modifications or chromatin state. However, these experiments remain too difficult/expensive for many laboratories to apply comprehensively to their system of interest. Here, we explore the potential of elucidating regulatory systems in varied cell types using computational techniques that rely on only data of gene expression, low-resolution chromatin accessibility, and TF–DNA binding specificities (‘motifs’). We show that static computational motif scans overlaid with chromatin accessibility data reasonably approximate experimentally measured TF–DNA binding. We demonstrate that predicted binding profiles and expression patterns of hundreds of TFs are sufficient to identify major regulators of ~200 spatiotemporal expression domains in the Drosophila embryo. We are then able to learn reliable statistical models of enhancer activity for over 70 expression domains and apply those models to annotate domain specific enhancers genome-wide. Throughout this work, we apply our motif and accessibility based approach to comprehensively characterize the regulatory network of fruitfly embryonic development and show that the accuracy of our computational method compares favorably to approaches that rely on data from many experimental assays.
    Schlagwort(e): Computational Methods, Genomics
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  • 80
    Publikationsdatum: 2015-06-24
    Beschreibung: Much of the inter-individual variation in gene expression is triggered via perturbations of signaling networks by DNA variants. We present a novel probabilistic approach for identifying the particular pathways by which DNA variants perturb the signaling network. Our procedure, called PINE, relies on a systematic integration of established biological knowledge of signaling networks with data on transcriptional responses to various experimental conditions. Unlike previous approaches, PINE provides statistical aspects that are critical for prioritizing hypotheses for followup experiments. Using simulated data, we show that higher accuracy is attained with PINE than with existing methods. We used PINE to analyze transcriptional responses of immune dendritic cells to several pathogenic stimulations. PINE identified statistically significant genetic perturbations in the pathogen-sensing signaling network, suggesting previously uncharacterized regulatory mechanisms for functional DNA variants.
    Schlagwort(e): Computational Methods, Genomics
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  • 81
    Publikationsdatum: 2015-08-29
    Beschreibung: Variations in sample quality are frequently encountered in small RNA-sequencing experiments, and pose a major challenge in a differential expression analysis. Removal of high variation samples reduces noise, but at a cost of reducing power, thus limiting our ability to detect biologically meaningful changes. Similarly, retaining these samples in the analysis may not reveal any statistically significant changes due to the higher noise level. A compromise is to use all available data, but to down-weight the observations from more variable samples. We describe a statistical approach that facilitates this by modelling heterogeneity at both the sample and observational levels as part of the differential expression analysis. At the sample level this is achieved by fitting a log-linear variance model that includes common sample-specific or group-specific parameters that are shared between genes. The estimated sample variance factors are then converted to weights and combined with observational level weights obtained from the mean–variance relationship of the log-counts-per-million using ‘voom’. A comprehensive analysis involving both simulations and experimental RNA-sequencing data demonstrates that this strategy leads to a universally more powerful analysis and fewer false discoveries when compared to conventional approaches. This methodology has wide application and is implemented in the open-source ‘limma’ package.
    Schlagwort(e): Computational Methods, Genomics
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  • 82
    Publikationsdatum: 2015-08-29
    Beschreibung: Most mammalian genes have mRNA variants due to alternative promoter usage, alternative splicing, and alternative cleavage and polyadenylation. Expression of alternative RNA isoforms has been found to be associated with tumorigenesis, proliferation and differentiation. Detection of condition-associated transcription variation requires association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on count data with replicates. Although the Cochran Mantel Haenszel (CMH) approach can handle replicated count data, our simulations showed that multiple CMH tests still had very low power. To identify condition-associated variation of transcription, we here proposed a ranking analysis of chi-squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric method and has accurate and conservative estimation of FDR profile. Simulations demonstrated that RAX2 performs well in finding condition-associated transcription variants. We applied RAX2 to primary T-cell transcriptomic data and identified 1610 (16.3%) tags associated in transcription with immune stimulation at FDR 〈 0.05. Most of these tags also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation short RNA isoforms were preferably used.
    Schlagwort(e): Computational Methods, Genomics
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  • 83
    Publikationsdatum: 2015-12-16
    Beschreibung: To understand how transposon landscapes (TLs) vary across animal genomes, we describe a new method called the Transposon Insertion and Depletion AnaLyzer (TIDAL) and a database of 〉300 TLs in Drosophila melanogaster (TIDAL-Fly). Our analysis reveals pervasive TL diversity across cell lines and fly strains, even for identically named sub-strains from different laboratories such as the ISO1 strain used for the reference genome sequence. On average, 〉500 novel insertions exist in every lab strain, inbred strains of the Drosophila Genetic Reference Panel (DGRP), and fly isolates in the Drosophila Genome Nexus (DGN). A minority (〈25%) of transposon families comprise the majority (〉70%) of TL diversity across fly strains. A sharp contrast between insertion and depletion patterns indicates that many transposons are unique to the ISO1 reference genome sequence. Although TL diversity from fly strains reaches asymptotic limits with increasing sequencing depth, rampant TL diversity causes unsaturated detection of TLs in pools of flies. Finally, we show novel transposon insertions negatively correlate with Piwi-interacting RNA (piRNA) levels for most transposon families, except for the highly-abundant roo retrotransposon. Our study provides a useful resource for Drosophila geneticists to understand how transposons create extensive genomic diversity in fly cell lines and strains.
    Schlagwort(e): Computational Methods, Genomics
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  • 84
    Publikationsdatum: 2015-04-21
    Beschreibung: Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free ( de novo ) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.
    Schlagwort(e): Computational Methods, Genomics
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  • 85
    Publikationsdatum: 2015-04-21
    Beschreibung: Distinguishing between promoter-like sequences in bacteria that belong to true or abortive promoters, or to those that do not initiate transcription at all, is one of the important challenges in transcriptomics. To address this problem, we have studied the genome-reduced bacterium Mycoplasma pneumoniae , for which the RNAs associated with transcriptional start sites have been recently experimentally identified. We determined the contribution to transcription events of different genomic features: the –10, extended –10 and –35 boxes, the UP element, the bases surrounding the –10 box and the nearest-neighbor free energy of the promoter region. Using a random forest classifier and the aforementioned features transformed into scores, we could distinguish between true, abortive promoters and non-promoters with good –10 box sequences. The methods used in this characterization of promoters can be extended to other bacteria and have important applications for promoter design in bacterial genome engineering.
    Schlagwort(e): Computational Methods, Genomics
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  • 86
    Publikationsdatum: 2015-04-21
    Beschreibung: MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods.
    Schlagwort(e): Computational Methods, Genomics
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  • 87
    Publikationsdatum: 2015-09-30
    Beschreibung: In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a β-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource ( larva.gersteinlab.org ).
    Schlagwort(e): Computational Methods, Genomics
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  • 88
    Publikationsdatum: 2015-12-02
    Beschreibung: Alu insertions have contributed to 〉11% of the human genome and ~30–35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means to reconstruct the full sequence of insertion events from Illumina paired end reads. Comparison with published calls obtained using PacBio long-reads indicates a false discovery rate below 5%, at the cost of reduced sensitivity due to the colocation of reference and non-reference repeats. We generate a highly accurate call set of 1614 completely assembled Alu variants from 53 samples from the Human Genome Diversity Project (HGDP) panel. We utilize the reconstructed alternative insertion haplotypes to genotype 1010 fully assembled insertions, obtaining 〉99% agreement with genotypes obtained by PCR. In our assembled sequences, we find evidence of premature insertion mechanisms and observe 5' truncation in 16% of Alu Ya5 and Alu Yb8 insertions. The sites of truncation coincide with stem-loop structures and SRP9/14 binding sites in the Alu RNA, implicating L1 ORF2p pausing in the generation of 5' truncations. Additionally, we identified variable Alu J and Alu S elements that likely arose due to non-retrotransposition mechanisms.
    Schlagwort(e): Computational Methods, Genomics
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  • 89
    Publikationsdatum: 2015-03-14
    Beschreibung: Mutual information (MI), a quantity describing the nonlinear dependence between two random variables, has been widely used to construct gene regulatory networks (GRNs). Despite its good performance, MI cannot separate the direct regulations from indirect ones among genes. Although the conditional mutual information (CMI) is able to identify the direct regulations, it generally underestimates the regulation strength, i.e. it may result in false negatives when inferring gene regulations. In this work, to overcome the problems, we propose a novel concept, namely conditional mutual inclusive information (CMI2), to describe the regulations between genes. Furthermore, with CMI2, we develop a new approach, namely CMI2NI (CMI2-based network inference), for reverse-engineering GRNs. In CMI2NI, CMI2 is used to quantify the mutual information between two genes given a third one through calculating the Kullback–Leibler divergence between the postulated distributions of including and excluding the edge between the two genes. The benchmark results on the GRNs from DREAM challenge as well as the SOS DNA repair network in Escherichia coli demonstrate the superior performance of CMI2NI. Specifically, even for gene expression data with small sample size, CMI2NI can not only infer the correct topology of the regulation networks but also accurately quantify the regulation strength between genes. As a case study, CMI2NI was also used to reconstruct cancer-specific GRNs using gene expression data from The Cancer Genome Atlas (TCGA). CMI2NI is freely accessible at http://www.comp-sysbio.org/cmi2ni .
    Schlagwort(e): Computational Methods, Genomics
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  • 90
    Publikationsdatum: 2015-04-02
    Beschreibung: High-throughput sequencing of DNA coding regions has become a common way of assaying genomic variation in the study of human diseases. Copy number variation (CNV) is an important type of genomic variation, but detecting and characterizing CNV from exome sequencing is challenging due to the high level of biases and artifacts. We propose CODEX, a normalization and CNV calling procedure for whole exome sequencing data. The Poisson latent factor model in CODEX includes terms that specifically remove biases due to GC content, exon capture and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based exome sequencing data. CODEX is compared to existing methods on a population analysis of HapMap samples from the 1000 Genomes Project, and shown to be more accurate on three microarray-based validation data sets. We further evaluate performance on 222 neuroblastoma samples with matched normals and focus on a well-studied rare somatic CNV within the ATRX gene. We show that the cross-sample normalization procedure of CODEX removes more noise than normalizing the tumor against the matched normal and that the segmentation procedure performs well in detecting CNVs with nested structures.
    Schlagwort(e): Computational Methods, Genomics
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  • 91
    Publikationsdatum: 2015-01-10
    Beschreibung: Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/ .
    Schlagwort(e): Computational Methods, Genomics
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  • 92
    Publikationsdatum: 2015-11-17
    Beschreibung: The prediction of novel pre-microRNA (miRNA) from genomic sequence has received considerable attention recently. However, the majority of studies have focused on the human genome. Previous studies have demonstrated that sensitivity (correctly detecting true miRNA) is sustained when human-trained methods are applied to other species, however they have failed to report the dramatic drop in specificity (the ability to correctly reject non-miRNA sequences) in non-human genomes. Considering the ratio of true miRNA sequences to pseudo-miRNA sequences is on the order of 1:1000, such low specificity prevents the application of most existing tools to non-human genomes, as the number of false positives overwhelms the true predictions. We here introduce a framework (SMIRP) for creating species-specific miRNA prediction systems, leveraging sequence conservation and phylogenetic distance information. Substantial improvements in specificity and precision are obtained for four non-human test species when our framework is applied to three different prediction systems representing two types of classifiers (support vector machine and Random Forest), based on three different feature sets, with both human-specific and taxon-wide training data. The SMIRP framework is potentially applicable to all miRNA prediction systems and we expect substantial improvement in precision and specificity, while sustaining sensitivity, independent of the machine learning technique chosen.
    Schlagwort(e): Computational Methods, Genomics
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  • 93
    Publikationsdatum: 2015-08-29
    Beschreibung: Statistical network modeling techniques are increasingly important tools to analyze cancer genomics data. However, current tools and resources are not designed to work across multiple diagnoses and technical platforms, thus limiting their applicability to comprehensive pan-cancer datasets such as The Cancer Genome Atlas (TCGA). To address this, we describe a new data driven modeling method, based on generalized Sparse Inverse Covariance Selection (SICS). The method integrates genetic, epigenetic and transcriptional data from multiple cancers, to define links that are present in multiple cancers, a subset of cancers, or a single cancer. It is shown to be statistically robust and effective at detecting direct pathway links in data from TCGA. To facilitate interpretation of the results, we introduce a publicly accessible tool ( cancerlandscapes.org ), in which the derived networks are explored as interactive web content, linked to several pathway and pharmacological databases. To evaluate the performance of the method, we constructed a model for eight TCGA cancers, using data from 3900 patients. The model rediscovered known mechanisms and contained interesting predictions. Possible applications include prediction of regulatory relationships, comparison of network modules across multiple forms of cancer and identification of drug targets.
    Schlagwort(e): Computational Methods, Genomics
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  • 94
    Publikationsdatum: 2015-07-25
    Beschreibung: Transposable elements (TEs) are mobile genomic DNA sequences found in most organisms. They so densely populate the genomes of many eukaryotic species that they are often the major constituents. With the rapid generation of many plant genome sequencing projects over the past few decades, there is an urgent need for improved TE annotation as a prerequisite for genome-wide studies. Analogous to the use of RNA-seq for gene annotation, we propose a new method for de novo TE annotation that uses as a guide 24 nt-siRNAs that are a part of TE silencing pathways. We use this new approach, called TASR (for Transposon Annotation using Small RNAs), for de novo annotation of TEs in Arabidopsis , rice and soybean and demonstrate that this strategy can be successfully applied for de novo TE annotation in plants. Executable PERL is available for download from: http://tasr-pipeline.sourceforge.net/
    Schlagwort(e): Computational Methods, Genomics
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  • 95
    Publikationsdatum: 2015-03-01
    Beschreibung: RNA-Seq is gradually becoming the standard tool for transcriptomic expression studies in biological research. Although considerable progress has been recorded in the development of statistical algorithms for the detection of differentially expressed genes using RNA-Seq data, the list of detected genes can differ significantly between algorithms. We present a new method (PANDORA) that combines multiple algorithms toward a summarized result, more efficiently reflecting true experimental outcomes. This is achieved through the systematic combination of several analysis algorithms, by weighting their outcomes according to their performance with realistically simulated data sets generated from real data. Results supported by the analysis of both simulated and real data from different organisms as well as correlation with PolII occupancy demonstrate that PANDORA improves the detection of differential expression. It accomplishes this by optimizing the tradeoff between standard performance measurements, such as precision and sensitivity.
    Schlagwort(e): Computational Methods, Genomics
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  • 96
    Publikationsdatum: 2015-02-18
    Beschreibung: We define a new category of candidate tumor drivers in cancer genome evolution: ‘selected expression regulators’ (SERs)—genes driving dysregulated transcriptional programs in cancer evolution. The SERs are identified from genome-wide tumor expression data with a novel method, namely SPARROW ( SPAR se selected exp R essi O n regulators identified W ith penalized regression). SPARROW uncovers a previously unknown connection between cancer expression variation and driver events, by using a novel sparse regression technique. Our results indicate that SPARROW is a powerful complementary approach to identify candidate genes containing driver events that are hard to detect from sequence data, due to a large number of passenger mutations and lack of comprehensive sequence information from a sufficiently large number of samples. SERs identified by SPARROW reveal known driver mutations in multiple human cancers, along with known cancer-associated processes and survival-associated genes, better than popular methods for inferring gene expression networks. We demonstrate that when applied to acute myeloid leukemia expression data, SPARROW identifies an apoptotic biomarker ( PYCARD ) for an investigational drug obatoclax. The PYCARD and obatoclax association is validated in 30 AML patient samples.
    Schlagwort(e): Computational Methods, Genomics
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  • 97
    Publikationsdatum: 2017-04-04
    Beschreibung: Since 2002 OGS (Istituto Nazionale di Oceanografia e di Geofisica Sperimentale) in Udine (Italy), the Zentralanstalt für Meteorologie und Geodynamik (ZAMG) in Vienna (Austria), and the Agencija Republike Slovenije za Okolje (ARSO) in Ljubljana (Slovenia) are using the Antelope software suite as the main tool for collecting, analyzing, archiving and exchanging seismic data in real time, initially in the framework of the EU Interreg IIIA project "Trans-national seismological networks in the South-Eastern Alps" (Bragato et al., 2004, 2010). The data exchange has proved to be effective and very useful in case of seismic events near the borders between Italy, Austria and Slovenia, where the poor single national seismic networks coverage precluded a correct localization, while the usage of common data from the integrated networks improves considerably the overall reliability of real time seismic monitoring of the area (Fig. 1). At the moment the data exchange between the seismic data centers relies on their internet connections: this however is not an ideal condition for civil protection purposes, since the reliability of standard internet connections is poor. For this reason in 2012 the Protezione Civile della Provincia Autonoma di Bolzano in Bolzano (PCBZ, Italy), OGS, ZAMG subsidiary in Tirol (ZAMG Tirol) and ARSO joined in the Interreg IV Italia-Austria Project "SeismoSAT" (Progetto SeismoSAT, 2012) aimed in connecting the seismic data centers in real time via satellite. ARSO does not belong to the Interreg Italia-Austria region: for this reason ARSO joined the SeismoSAT project as an "associated partner", which, according to Interreg rules can not be funded. ARSO participation in the project is therefore at the beginning limited in benefiting only indirectly from improvement in the robustness of the data exchange between the other data centers, while eventually fully taking part in the project if other sources of funding will be available. The project is in a preliminary phase: the general schema of the project, including first data bandwidth estimates and a possible architecture are here illustrated.
    Beschreibung: Published
    Beschreibung: 57-60
    Beschreibung: 1IT. Reti di monitoraggio e Osservazioni
    Beschreibung: N/A or not JCR
    Beschreibung: open
    Schlagwort(e): satellite ; SeismoSAT ; seismic data centers ; 04. Solid Earth::04.06. Seismology::04.06.06. Surveys, measurements, and monitoring
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 98
    Publikationsdatum: 2017-04-04
    Beschreibung: The Centro di Ricerche Sismologiche (CRS, Seismological Research Centre) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the North-eastern Italy Seismic Network: it currently consists of 17 very sensitive broad band and 18 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data centre in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of about 100 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of North-eastern Italy. The south-western edge of the OGS seismic network (Fig. 1) stands on the Po alluvial basin: earthquake localization and characterization in this area is affected by the presence of soft alluvial deposits. OGS ha already experience in running a local seismic network in high noise conditions making use of borehole installations in the case of the micro-seismicity monitoring of a local gas storage site for a private company. Following the ML = 5.9 earthquake that struck the Emilia region around Ferrara in Northern Italy on 20 May 2012 at 02:03:53 UTC, a cooperation of Istituto Nazionale di Geofisica e Vulcanologia, OGS, the Comune di Ferrara and the University of Ferrara lead to the reinstallation of a previously existing very broad band (VBB) borehole seismic station in Ferrara. The aim of the OGS intervention was on one hand to extend its real time seismic monitoring capabilities toward South-West, including Ferrara and its surroundings, and on the other hand to evaluate the seismic response at the site. We will describe improvements in running the North-eastern Italy Seismic Network, including details of the Ferrara VBB borehole station configuration and installation, with first results.
    Beschreibung: Regione Veneto
    Beschreibung: Published
    Beschreibung: 61-67
    Beschreibung: 1IT. Reti di monitoraggio e Osservazioni
    Beschreibung: N/A or not JCR
    Beschreibung: open
    Schlagwort(e): borehole seismic ; Ferrara ; OGS ; 04. Solid Earth::04.06. Seismology::04.06.06. Surveys, measurements, and monitoring
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 99
    Publikationsdatum: 2014-11-07
    Beschreibung: A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/ .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    facet.materialart.
    Unbekannt
    Oxford University Press
    Publikationsdatum: 2014-11-28
    Beschreibung: It is now known that unwanted noise and unmodeled artifacts such as batch effects can dramatically reduce the accuracy of statistical inference in genomic experiments. These sources of noise must be modeled and removed to accurately measure biological variability and to obtain correct statistical inference when performing high-throughput genomic analysis. We introduced surrogate variable analysis (sva) for estimating these artifacts by (i) identifying the part of the genomic data only affected by artifacts and (ii) estimating the artifacts with principal components or singular vectors of the subset of the data matrix. The resulting estimates of artifacts can be used in subsequent analyses as adjustment factors to correct analyses. Here I describe a version of the sva approach specifically created for count data or FPKMs from sequencing experiments based on appropriate data transformation. I also describe the addition of supervised sva (ssva) for using control probes to identify the part of the genomic data only affected by artifacts. I present a comparison between these versions of sva and other methods for batch effect estimation on simulated data, real count-based data and FPKM-based data. These updates are available through the sva Bioconductor package and I have made fully reproducible analysis using these methods available from: https://github.com/jtleek/svaseq .
    Schlagwort(e): Computational Methods, Genomics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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