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  • Computational Methods  (36)
  • 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring  (22)
  • Oxford University Press  (36)
  • American Geophysical Union  (20)
  • INGV  (1)
  • Molecular Diversity Preservation International  (1)
  • 2015-2019  (58)
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  • 1945-1949
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  • 1
    Publication Date: 2020-12-14
    Description: Explosive volcanic eruptions are defined as the violent ejection of gas and hot fragments from a vent in the Earth's crust. Knowledge of ejection velocity is crucial for understanding and modeling relevant physical processes of an eruption, and yet direct measurements are still a difficult task with largely variable results. Here we apply pioneering high-speed imaging to measure the ejection velocity of pyroclasts from Strombolian explosive eruptions with an unparalleled temporal resolution. Measured supersonic velocities, up to 405 m/s, are twice higher than previously reported for such eruptions. Individual Strombolian explosions include multiple, sub-second-lasting ejection pulses characterized by an exponential decay of velocity. When fitted with an empirical model from shock-tube experiments literature, this decay allows constraining the length of the pressurized gas pockets responsible for the ejection pulses. These results directly impact eruption modeling and related hazard assessment, as well as the interpretation of geophysical signals from monitoring networks.
    Description: INGV-DPC “V2” and “Paroxysm”, FIRB-MIUR “Research and Development of New Technologies for Protection and Defense of Territory from Natural Risks”, and FP7-PEOPLE-IEF-2008 – 235328 Projects
    Description: Published
    Description: L02301
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: open
    Keywords: strombolian ; ejection velocity ; explosive eruption ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2021-02-10
    Description: Continuous gravity data collected near the summit eruptive vent at Kīlauea Volcano, Hawaiʻi, during 2011–2015 show a strong correlation with summit-area surface deformation and the level of the lava lake within the vent over periods of days to weeks, suggesting that changes in gravity reflect variations in volcanic activity. Joint analysis of gravity and lava level time series data indicates that over the entire time period studied, the average density of the lava within the upper tens to hundreds of meters of the summit eruptive vent remained low—approximately 1000–1500 kg/m^3. The ratio of gravity change (adjusted for Earth tides and instrumental drift) to lava level change measured over 15 day windows rose gradually over the course of 2011–2015, probably reflecting either (1) a small increase in the density of lava within the eruptive vent or (2) an increase in the volume of lava within the vent due to gradual vent enlargement. Superimposed on the overall time series were transient spikes of mass change associated with inflation and deflation of Kīlauea’s summit and coincident changes in lava level. The unexpectedly strong mass variations during these episodes suggest magma flux to and from the shallow magmatic system without commensurate deformation, perhaps indicating magma accumulation within, and withdrawal from, void space—a process that might not otherwise be apparent from lava level and deformation data alone. Continuous gravity data thus provide unique insights into magmatic processes, arguing for continued application of the method at other frequently active volcanoes.
    Description: Published
    Description: 5477–5492
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Kīlauea Volcano; gravity changes; lava lake; volcano monitoring ; 04. Solid Earth::04.02. Exploration geophysics::04.02.02. Gravity methods ; 04. Solid Earth::04.03. Geodesy::04.03.05. Gravity variations ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 3
    Publication Date: 2021-03-01
    Description: A new period of eruptive activity started at Turrialba volcano, Costa Rica, in 2010 after almost 150 years of quiescence. This activity has been characterized by sporadic explosions whose frequency clearly increased since October 2014. This study aimed to identify the mechanisms that triggered the resumption of this eruptive activity and characterize the evolution of the phenomena over the past 2 years. We integrate 3He/4He data available on fumarole gases collected in the summit area of Turrialba between 1999 and 2011 with new measurements made on samples collected between September 2014 and February 2016. The results of a petrological investigation of the products that erupted between October 2014 and May 2015 are also presented. We infer that the resumption of eruptive activity in 2010 was triggered by a replenishment of the plumbing system of Turrialba by a new batch of magma. This is supported by the increase in 3He/4He values observed since 2005 at the crater fumaroles and by comparable high values in September 2014, just before the onset of the new eruptive phase. The presence of a number of fresh and juvenile glassy shards in the erupted products increased between October 2014 and May 2015, suggesting the involvement of new magma with a composition similar to that erupted in 1864–1866. We conclude that the increase in 3He/4He at the summit fumaroles since October 2015 represents strong evidence of a new phase of magma replenishment, which implies that the level of activity remains high at the volcano.
    Description: Published
    Description: 3V. Proprietà dei magmi e dei prodotti vulcanici
    Description: 4V. Dinamica dei processi pre-eruttivi
    Description: 5V. Dinamica dei processi eruttivi e post-eruttivi
    Description: JCR Journal
    Keywords: Turrialba volcano ; eruptive activity ; 3He/4He ; fumarole gases ; glassy shards ; juvenile component ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.07. Tectonophysics::04.07.08. Volcanic arcs ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 04. Solid Earth::04.08. Volcanology::04.08.05. Volcanic rocks ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 4
    Publication Date: 2020-12-15
    Description: We have analyzed a focal mechanism data set for Mount Vesuvius, consisting of 197 focal mechanisms of events recorded from 1999 to 2012. Using different approaches and a comparison between observations and numerical models, we have determined the spatial variations in the stress field beneath the volcano. The main results highlight the presence of two seismogenic volumes characterized by markedly different stress patterns. The two volumes are separated by a layer where the seismic strain release shows a significant decrease. Previous studies postulated the existence, at about the same depth, of a ductile layer allowing the spreading of the Mount Vesuvius edifice. We interpreted the difference in the stress pattern within the two volumes as the effect of a mechanical decoupling caused by the aforementioned ductile layer. The stress pattern in the top volume is dominated by a reverse faulting style, which agrees with the hypothesis of a seismicity driven by the spreading process. This agrees also with the persistent character of the seismicity located within this volume. Conversely, the stress field determined for the deep volume is consistent with a background regional field locally perturbed by the effects of the topography and of heterogeneities in the volcanic structure. Since the seismicity of the deep volume shows an intermittent behavior and has shown to be linked to geochemical variations in the fumaroles of the volcano, we hypothesize that it results from the effect of fluid injection episodes, possibly of magmatic origin, perturbing the pore pressure within the hydrothermal system.
    Description: Published
    Description: 1181–1199
    Description: 4T. Fisica dei terremoti e scenari cosismici
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: JCR Journal
    Description: restricted
    Keywords: vesuvius ; stress inversion ; focal mechanisms ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology ; 04. Solid Earth::04.06. Seismology::04.06.10. Instruments and techniques ; 04. Solid Earth::04.07. Tectonophysics::04.07.05. Stress ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 5
    Publication Date: 2021-04-07
    Description: Integrating geodetic, seismic, and petrological data for a recent eruptive episode at Mount Etna has enabled us to define the history of magma storage and transfer within the multilevel structure of the volcano, providing spatial and temporal constraints for magma movements before the eruption. Geodetic data related to the July–August 2014 activity provide evidence of a magma reservoir at ~4 km below sea level. This reservoir pressurized from late March 2014 and fed magmas that were then erupted from vents on the lower eastern flank of North-East Crater (NEC) and at New South-East Crater (NSEC) summit crater during the July eruptive activity. Magma drainage caused its depressurization since mid-July. Textural and microanalytical data obtained from plagioclase crystals indicate similar disequilibrium textures and compositions at the cores in lavas erupted at the base of NEC and NSEC, suggesting comparable deep histories of evolution and ascent. Conversely, the compositional differences observed at the crystal rims have been associated to distinct degassing styles during storage in a shallow magma reservoir. Seismic data have constrained depth for a shallow part of the plumbing system at 1–2 km above sea level. Timescales of magma storage and transfer have also been calculated through diffusion modeling of zoning in olivine crystals of the two systems. Our data reveal a common deep history of magmas from the two systems, which is consistent with a recharging phase by more mafic magma between late March and early June 2014. Later, the magma continued its crystallization under distinct chemical and physical conditions at shallower levels.
    Description: The petrological part of this study was supported by the FIR 2014 research grant to Marco Viccaro from the University of Catania (Italy), grant number 2F119B, title of the project “Dynamics of evolution, ascent and emplacement of basic magmas: case-studies from eruptive manifestations of Eastern Sicily”.
    Description: Published
    Description: 5659–5678
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Petrology ; eruption ; GPS ; volcano seismology ; Etna ; 04. Solid Earth::04.03. Geodesy::04.03.01. Crustal deformations ; 04. Solid Earth::04.03. Geodesy::04.03.07. Satellite geodesy ; 04. Solid Earth::04.04. Geology::04.04.07. Rock geochemistry ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 6
    Publication Date: 2017-04-04
    Description: A new eruption started at Stromboli on August 6, 2014, which had been preceded by 2 months of increased Strombolian activity and several lava overflows from the craters. The eruption was characterized by a lava effusion in Sciara del Fuoco from a fracture at 650 m a.s.l. that lasted until November 13–17. Here we present the first geochemical observations of this eruption, based on the soil CO2 flux in the summit area, and on 3He/4He ratios in the thermal waters near Stromboli village. We infer that this eruption was triggered by the gradual replenishment of the feeding system by a CO2- and 3He-rich magma at the end of 2013 and after June 2014, suggested by the increase in 3He/4He ratio before eruption, which reached its highest value since 2007. We thus infer that this eruption was unusual and we finally speculate on the evolutionary scenario of post eruption.
    Description: Published
    Description: 2235–2243
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 3V. Dinamiche e scenari eruttivi
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: JCR Journal
    Description: restricted
    Keywords: Stromboli ; eruption ; soil CO2 flux ; 3He/4He ratio ; thermal waters ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 7
    Publication Date: 2017-04-04
    Description: The marine sector of the Campi Flegrei caldera has started to be monitored over the long-term with a seafloor equipment deployed in the Gulf of Pozzuoli from 2008. The equipment includes a set of geophysical, oceanographic and environmental sensors integrated in a marine platform that was specifically designed for real-time monitoring. This platform, named CUMAS (Cabled Underwater Multidisciplinary Acquisition System), was installed in the center of the Gulf at about 2.5 km south of Pozzuoli where the sea depth is about 100 m [Iannaccone et al., 2010]. The CUMAS system consists of a seafloor module connected by cable to a buoy (elastic beacon type) equipped with autonomous power supply systems, real-time data- transmission devices and a weather station. The core of CUMAS is the seafloor module that contains geophysical and oceanographic sensors, in particular, a three-component broadband seismometer, a best in class three axis MEMS accelerometer, a low-frequency hydrophone and a high-resolution sea bottom pressure recorder. A single-point acoustic, three-component, water-current meter and a water-temperature sensor were also installed to monitor some water local physical parameters. A set of status sensors, which also included a digital compass and a two-component digital tilt-meter, were added to track the attitude of the module over the course of the experiment. The marine monitoring system transmits the data in real-time and is integrated into the Monitoring Center in Naples managed by INGV-Osservatorio Vesuviano. A continuous GPS station has been installed since the end of 2011 on the top of the buoy. The elastic beacon buoy forms a structure which is rigidly connected by a mechanical cable to the ballast on the sea bottom, a submerged float at the base of the buoy maintains tension on the cable and ensure the overall buoyancy of the system. In this way, any vertical movement of the seafloor propagates rigidly to the emerged part of the buoy itself, allowing measurement of the vertical movement of the sea floor by the GPS station. The analysis of about 17 months of continuous GPS data, from January 2012 to May 2013, revealed an overall uplift of about 3-4 cm allowing a first measurement of vertical seafloor displacement in the Campi Flegrei caldera [De Martino et al., 2014]. A new opportunity to enhance the deployed system was given by a national project, EMSO-MedIT, which is providing the necessary resources to expand the data acquisition to other areas of the Gulf of Pozzuoli. New improved systems similar to CUMAS are going to be deployed in three additional marine sites of the Gulf of Pozzuoli and the existing tide gauges network will be renewed with state-of-art sensors. The overall new monitoring infrastructure will allow to extensively map the seafloor vertical displacement and to improve the interpretative models of the bradyseism phenomenon including a more accurate location of earthquakes in the marine areas and extending to lower magnitude values the detection of the seismic activity.
    Description: INGV, Comune di Nicolosi, Parco dell'Etna, Funivia dell'Etna
    Description: Published
    Description: Nicolosi (Catania) -I TALY
    Description: 1IT. Reti di monitoraggio e Osservazioni
    Description: open
    Keywords: Monitoring System in Marine Sector ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Conference paper
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  • 8
    Publication Date: 2020-02-24
    Description: This work arises from the field observations made during the civil protection emergency period connected to the 2007 Stromboli eruption. We observed changes in the shallow feeding system of the volcano to which we give a volcanological interpretation and the relative implications. Here we describe the processes that occurred in the upper feeding system from the end of the 2007 effusive eruption on 3 April to the renewal of the strombolian explosive activity at the summit craters (30 June), interpreted using multidisciplinary data. We used thermal camera data collected both from helicopter and from a fixed station at 400 m to retrieve the evolving summit crater activity. These data, compared with seismic signals and published geochemical records, allowed us to detail the shifting of the degassing activity within the crater terrace from NE to SW, occurred between 15 and 25 April 2007 prior to the resumption of the strombolian activity. In particular, from mid-April, a gradual SW displacement in the maximum apparent temperatures was recorded at the vents within the summit craters, together with a change in the very long period location and confirmed by variations in geochemical indicators (CO2∕SO2 plume ratios and CO2 fluxes) from literature. The shallow feeding system experienced a major readjustment after the end of the effusive activity, determining variations in the pressure leakage of the source, slowly deepening and shifting toward SW. All these data, together with the framework supplied by previous structural surveys, allowed us to propose that the compaction of debris accumulated in the uppermost conduit by inward crater collapses, occurred in early March, produced the observed anomalies. At Stromboli, major morphology changes, taking place in the following years, were anticipated by these small and apparently minor processes occurred in the upper feeding system. Other studies are relating similar changes to modifications of the eruptive activity also at other open-conduit volcanoes, so we believe that it may be important to have a constant monitoring of these phenomena in order to better understand their shallow feeding systems.
    Description: This paper was partially supported by a grant to S.C. (Project INGV-DPC Paroxysm V2/03, 2008–2010) funded by the Istituto Nazionale di Geofisica e Vulcanologia and by the Italian Civil Protection.
    Description: Published
    Description: 7376–7395
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Stromboli volcano ; thermal imaging ; multidisciplinary study ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
    Publication Date: 2017-04-04
    Description: An array of nine three-component broadband seismometers was deployed in two different configurations on Stromboli volcano. The analysis of the seismic wavefield related to volcanic explosions revealed some observations which offer a completely new insight into the internal dynamics of a volcano. These new observations are restricted to the low-frequency range below 1 Hz and underline, therefore, the superiority of broadband recordings over conventional short-period observations. Surprisingly simple wavelets indicate an initially contracting source mechanism. Gas-jets that could not be seen in a short-period seismic record at all, generate a clear dilatational wavelet in a broadband recording suggesting the same contracting source mechanism. The analysis of particle motion and seismic array techniques permits a location of the seismic source. We find low-frequency signals of 3s and 6s period that are not related to eruptions and do not share a common source with the eruption-related events. A video recording of visible volcanic activity at the crater region allows one to correlate precisely eruptive features with seismic signals.
    Description: Published
    Description: 749-752
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: N/A or not JCR
    Description: restricted
    Keywords: Stromboli ; volcano seismology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
    Publication Date: 2017-04-04
    Description: High-speed imaging of explosive eruptions at Stromboli (Italy), Fuego (Guatemala), and Yasur (Vanuatu) volcanoes allowed visualization of pressure waves from seconds-long explosions. From the explosion jets, waves radiate with variable geometry, timing, and apparent direction and velocity. Both the explosion jets and their wave fields are replicated well by numerical simulations of supersonic jets impulsively released from a pressurized vessel. The scaled acoustic signal from one explosion at Stromboli displays a frequency pattern with an excellent match to those from the simulated jets. We conclude that both the observed waves and the audible sound from the explosions are jet noise, i.e., the typical acoustic field radiating from high-velocity jets. Volcanic jet noise was previously quantified only in the infrasonic emissions from large, sub-Plinian to Plinian eruptions. Our combined approach allows us to define the spatial and temporal evolution of audible jet noise from supersonic jets in small-scale volcanic eruptions.
    Description: INGV-DPC “V2” and “Paroxysm,” FIRB-MIUR “Research and Development of New Technologies for Protection and Defense of Territory from Natural Risks,” and FP7-PEOPLE-IEF-2008–235328 “NEMOH” ITN projects
    Description: Published
    Description: 3096–3102
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: jet noise ; volcano acoustics ; Stromboli ; Yasur ; Fuego ; strombolian eruption ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 11
    Publication Date: 2017-04-04
    Description: The fumarolic gas output has not been quantified for any of the currently deforming calderas worldwide, due to the lack of suitable gas flux sensing techniques. In view of resumption of ground uplift (since 2005) and the associated variations in gas chemistry, Campi Flegrei, in southern Italy, is one of the restless calderas where gas flux observations are especially necessary. Here we report the first ever obtained estimate of the Campi Flegrei fumarolic gas output, based on a set of MultiGAS surveys (performed in 2012 and 2013) with an ad-hoc-designed measurement setup. We estimate that the current Campi Flegrei fumarolic sulphur (S) flux is low, on the order of 1.5–2.2 tons/day, suggesting substantial scrubbing of magmatic S by the hydrothermal system. However, the fumarolic carbon dioxide (CO2) output is ∼460±160 tons/day (mean±SD), which is surprisingly high for a dormant volcano in the hydrothermal stage of activity, and results in a combined (fumaroles + soil) CO2 output of ∼1560 tons/day. Assuming magma to be the predominant source, we propose that the current CO2 output can be supplied by either (i) a large (0.6–4.6 km3), deeply stored (〉7 km) magmatic source with low CO2 contents (0.05–0.1 wt%) or (ii) by a small to medium-sized (∼0.01–0.1 km3) but CO2-rich (2 wt%) magma, possibly stored at pressures of ∼100 to 120 MPa. Independent geophysical evidence (e.g., inferred from geodetic and gravity data) is needed to distinguish between these two possibilities.
    Description: Published
    Description: 4153–4169
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Campi Flegrei ; calderas ; gas output ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 12
    Publication Date: 2017-04-04
    Description: The interpretation of dynamic processes that occur in volcanic calderas is not simple. The ground deformations and the local seismicity, which in other volcanic contexts are usually regarded as precursors to eruption, in caldera environment in many cases are not followed by any eruption. We formulate a general hypothesis that can explain these behaviors. Our hypothesis is that the intrusion of a sill can be responsible for the dynamics observed during unrest at calderas. In order to investigate the reliability of this hypothesis, we developed a dynamic model of sill intrusion in a shallow volcanic environment. In our model, the sill, fed by a deeper magma reservoir, intrudes below a horizontal elastic plate, representing the overlying rocks, and expands with axisymmetric geometry. The model is based on the numerical solution of the equation for the elastic plate, coupled with a Navier-Stokes equation for simulating the dynamics of the sill intrusion. We performed a number of simulations, with the objective of showing the main features of the model. In the experiments, when the feeding process stops, the vertical movement reverses its trend and the area of maximum uplift undergoes subsidence. Under certain conditions the subsidence can occur even during the intrusion of the sill. The stress field produced by the intrusion is mainly concentrated in a circular zone that follows the sill intrusion front. The features predicted by the model are consistent with many observations carried out on different calderas as reported in the scientific literature.
    Description: Published
    Description: 3986–4000
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 3V. Dinamiche e scenari eruttivi
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: JCR Journal
    Description: restricted
    Keywords: sill intrusion ; caldera ; volcano geodesy ; 04. Solid Earth::04.03. Geodesy::04.03.01. Crustal deformations ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.05. Mathematical geophysics::05.05.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 13
    Publication Date: 2017-04-04
    Description: Mt Etna volcano (Italy) typically generates lava fountains and Strombolian eruptions from the summit craters, producing significant emissions of tephra which may cause moderate to high impact both in the atmosphere and on the ground. However, we have also witnessed a number of minor ash emissions that, although far less powerful, may pose considerable volcanic hazards. In this paper, we deal with three ash emissions occurring in 2010 (8 April at Southeast Crater, 25 August at Bocca Nuova, and 14–15 November at Northeast Crater), correlating their volcanological features with the associated seismoacoustic signals. We provide details regarding the chronology, eruption column, dispersal of the deposit, and texture (grain size, componentry and morphology) of the emitted ash. Each eruptive episode has also been characterized by means of seismo-acoustic analyses evaluating the volcanic acoustic-seismic ratio (VASR). Furthermore, the source of volcanic tremor recorded from March to December 2010 was localized. The joint volcanological and seismo-acoustic analyses allowed distinguishing two main kinds of ash emissions: types a (8 April and 25 August) and b (14–15 November). Regarding the former, the accumulation of gas below a dense cap rock obstructing the conduit vent, giving rise, with the uncorking, to impulsive explosivity, was hypothesized. The latter type instead is characterized by a longer-lasting and less explosivity, likely due to the existence of open conduit conditions. Therefore, type b ash emissions are less hazardous than type a. This simple model, regarding minor explosive activity, may constitute a starting point to assess the volcanic risk from unexpected explosions.
    Description: Published
    Description: 51-70
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: reserved
    Keywords: Mt Etna ; seismo-acoustic signals ; ash emissions ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 14
    Publication Date: 2017-04-04
    Description: Between January 2011 and April 2013, Mt. Etna's eruptive activity consisted of episodic intra-crater strombolian explosions and paroxysms from Bocca Nuova, Voragine, and the New South-East (NSEC) summit craters, respectively. Eruptions from NSEC consisted of initial increasing strombolian activity and lava flow output, passing to short-lasting lava fountaining. In this study we present seismic, infrasound, radiometric, plume SO2 and HCl fluxes and geodetic data collected by the INGV monitoring system between May 2012 and April 2013. The multi-parametric approach enabled characterization of NSEC eruptive activity at both daily and monthly time scales and tracking of magma movement within Mt. Etna's plumbing system. While seismic, infrasound and radiometric signals give insight on the energy and features of the 13 paroxysms fed by NSEC, SO2 and halogen fluxes shed light on the likely mechanisms triggering the eruptive phenomena. GPS data provided clear evidence of pressurization of Mt. Etna's plumbing system from May 2012 to middle February 2013 and depressurization during the February-April 2013 eruptive activity. Taking into account geochemical data, we propose that the paroxysms' sequence represented the climax of a waxing-waning phase of degassing that had started as early as December 2012, and eventually ended in April 2013. Integration of the multidisciplinary observations suggests that the February-April 2013 eruptive activity reflects a phase of release of a volatile-rich batch of magma that had been stored in the shallow volcano plumbing system at least four months before, and with the majority of gas released between February and March 2013. This article is protected by copyright. All rights reserved.
    Description: European FP7 MED-SUV (MEditerranean SUpersite Volcanoes). Grant Number: 308665 European Research Council European FP7 (FP/2007-2013)/ERC. Grant Number: 279802 SIGMA (Sistema Integrato di sensori in ambiente cloud per la Gestione Multirischio Avanzata)
    Description: Published
    Description: 1932–1949
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Mt. Etna ; paroxysmal activity ; SO2 and HCl fluxes ; infrasound and seismic signals ; radiometry ; ground deformation ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 15
    Publication Date: 2017-04-04
    Description: We present the results of laboratory experiments on the aggregation and disaggregation of colliding volcanic ash particles. Ash particles of different composition and size 〈90 µm were held in turbulent suspension and filmed in high speed while colliding, aggregating, and disaggregating, forming a growing layer of electrostatically bound particles along a vertical plate. At room conditions and regardless of composition, 60–80% of the colliding particles smaller than 32 µm remained aggregated. In contrast, aggregation of particles larger than 63 µm was negligible, and, when a layer formed, periods when disaggregation (mainly by collisions or drag) exceeded aggregation occurred twice as frequently than for smaller particles. An empirical relationship linking the aggregation index, i.e., the effective fraction of aggregated particles surviving disaggregation, to the mean particle collision kinetic energy is provided. Our results have potential implications on the dynamics of volcanic plumes and ash mobility in the environment.
    Description: INGV-DPC project V1 “Probabilistic evaluation of volcanic hazard”; EU Seventh Programme FP7 “MED-SUV” grant agreement 308665
    Description: Published
    Description: 1068–1075
    Description: 3V. Dinamiche e scenari eruttivi
    Description: 2IT. Laboratori sperimentali e analitici
    Description: JCR Journal
    Description: restricted
    Keywords: volcanic ash ; disaggregation ; experimental modeling ; volcanic plumes ; aggregation processes ; colliding particles ; sticking rate ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.02. Experimental volcanism ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 16
    Publication Date: 2017-04-04
    Description: Piton de la Fournaise (PdF) is recognised as one of the world’s most active volcanoes in terms of eruptive frequency and the substantial quantity of lava produced. Yet, with the sole exception of rather modest intracrateric fumarole activity, this seems to be in contrast with an apparent absence of any type of natural fluid emission during periods of quiescence. Measurement campaigns were undertaken during a long-lasting quiescent period (2012-2014) and just after a short lived summit eruption (June 2014) in order to identify potential degassing areas in relation to the main structural features of the volcano (ex. rift zones) with the aim of developing a broader understanding of the geometry of the plumbing and degassing system. In order to assess the possible existence of anomalous soil CO2 flux, 513 measurements were taken along transects roughly orthogonal to the known tectonic lineaments crossing PdF edifice. In addition, 53 samples of gas for C isotope analysis were taken at measurement points that showed a relatively high CO2 concentration in the soil. CO2 flux values range from 10 to 1300 g m-2 d-1 while 13C are between -26.6 to -8‰. The results of our investigation clearly indicate that there is a strong spatial correlation between the anomalous high values of diffusive soil emissions and the main rift zones cutting the PdF massif and, moreover, that generally high soil CO2 fluxes show a d13C signature clearly related to a magmatic origin.
    Description: INSU (CNRS) and La Réunion Préfecture (Projet pour la quantification de l’aléa volcanique à La Réunion)
    Description: Published
    Description: 4388–4404
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: CO2 soil degassing anomalies at Piton de la Fournaise ; d13C magmatic signature ; Close link between anomalous CO2 degassing and the main seismotectonic structures ; 04. Solid Earth::04.02. Exploration geophysics::04.02.01. Geochemical exploration ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.07. Tectonophysics::04.07.07. Tectonics ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 17
    Publication Date: 2017-04-04
    Description: This paper focuses on the chemical composition changes in soil gases through both a theoretical model and laboratory experiments. The model describes the one-dimensional mass transfer process, which is triggered by changes in the flux parameters of the system, and the time-dependent evolution of the composition of the soil gases as a function of i) the pristine gas mixture, ii) the diffusivity of the chemicals, and iii) the thickness of the transited medium. Carbon dioxide (CO2), hydrogen (H2), and helium (He) were used in a laboratory-scale flux simulator to investigate the evolution of the gas composition profile in an artificial soil of constant thickness. The agreement between the theoretical calculations and the experimental results supports the validity of the model. Our results indicate a good reproducibility of the transient changes in the concentrations of CO2, He, and H2 in CO2-rich gas mixtures that contain He and H2 as trace gases. Finally, the theoretical results were used to analyze the H2 and CO2 continuous monitoring data collected at Etna volcano in 2010
    Description: Published
    Description: 1565–1583
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: 1IT. Reti di monitoraggio e Osservazioni
    Description: JCR Journal
    Description: open
    Keywords: Soil gases ; Volcanic gas composition ; Hydrogen ; Carbon dioxide ; CO2 ; Helium ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 18
    Publication Date: 2017-04-04
    Description: On 28 December 2014, eruptive activity resumed at Mount Etna with fire fountain activity feeding two lava flows on the eastern and southwestern upper flanks of the volcano. Unlike all previous summit activity, this eruption produced clear deformation at the summit of the volcano. GPS displacements and Sentinel-1A ascending interferogramswere calculated in order to image the ground deformation pattern accompanying the eruption. The displacements observed by GPS depict a local ground deformation pattern, affecting only the upperpart of the volcano.Despite snowcover onthe summit, differential interferometry synthetic aperture radar (DInSAR) data allowed obtainingmore detail onthe grounddeformation pattern on the upper eastern side of the volcano. Three-dimensional GPS displacements inversion located a very shallow NE-SW intrusion just beneath the New Southeast Crater. However, this model cannot justify all the deformation observed by DInSAR thus revealing a gravitational failure of the lava flow field
    Description: Published
    Description: 2727–2733
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: restricted
    Keywords: Sentinel-1A interferogram details the ground deformation field ; GPS data are analyzed for modeling the dyke intrusion ; Data comparison highlights an incipient slope failure ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 19
    Publication Date: 2017-04-04
    Description: During volcanic eruptions, measurements of the rate at which magma is erupted underpin hazard assessments. For eruptions dominated by the effusion of lava, estimates are often made using satellite data; here, in a case study at Mount Etna (Sicily), we make the first measurements based on terrestrial laser scanning (TLS), and we also include explosive products. During the study period (17–21 July 2012), regular Strombolian explosions were occurring within the Bocca Nuova crater, producing a ~50 m-high scoria cone and a small lava flow field. TLS surveys over multi-day intervals determined a mean cone growth rate (effusive and explosive products) of ~0.24 m3·s−1. Differences between 0.3-m resolution DEMs acquired at 10-minute intervals captured the evolution of a breakout lava flow lobe advancing at 0.01–0.03 m3·s−1. Partial occlusion within the crater prevented similar measurement of the main flow, but integrating TLS data with time-lapse imagery enabled lava viscosity (7.4 × 105 Pa·s) to be derived from surface velocities and, hence, a flux of 0.11 m3·s−1 to be calculated. Total dense rock equivalent magma discharge estimates are ~0.1–0.2 m3·s−1 over the measurement period and suggest that simultaneous estimates from satellite data are somewhat overestimated. Our results support the use of integrated TLS and time-lapse photography for ground-truthing space-based measurements and highlight the value of interactive image analysis when automated approaches, such as particle image velocimetry (PIV), fail.
    Description: Published
    Description: 14967 - 14987
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: open
    Keywords: lava flow; scoria cone; effusion rate; terrestrial laser scanning; time-lapse photography; Mt. Etna ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 20
    Publication Date: 2017-04-04
    Description: To evaluate the volcanic processes leading to the 25–26 October 2013 lava fountain at Mount Etna, we jointly investigated gravity, GPS, and DInSARmeasurements covering the late-June to early-November time interval. We used finite element modeling to infer a shallow magmatic reservoir which (i) inflated since July 2013, (ii) fed the volcanic activity at the summit craters during 25–26 October, and (iii) deflated due to magma drainage related to this volcanic activity. We suggested that this reservoir belongs to a shallow volume, which is located beneath the summit area and is replenished by magma rising from deep reservoirs and fed the short-term volcanic activity, representing a persistent shallow magmatic plumbing system of Etna. In addition, the model results show that there is a large discrepancy between the erupted and shallow reservoir deflation volumes, which could be reasonably attributable to a highly compressible volatile-rich magma.
    Description: Published
    Description: 3246–3253
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: JCR Journal
    Description: open
    Keywords: Gravity and deformation signatures of the 26 October 2013 Mount Etna lava fountain ; Integrated finite element-based inversion of gravity and GPS data ; Inference on a highly compressible volatile-rich magma in the magmatic reservoir ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 21
    Publication Date: 2021-12-15
    Description: Relationships between frequency and intensity of volcanic eruptions are actively sought by geophysicists for both monitoring and research purposes. By analyzing surveillance videos of persistent volcanic activity at Stromboli (Italy), we derived the frequency and jet height of 〉4000 explosions that occurred in 72 h-long time windows sampled yearly from 2005 to 2009. We found a positive relationship linking explosion frequency and jet height (linked to eruption intensity) when averaging the two parameters over time intervals from hours to days, with a stronger correlation for longer intervals. We interpret this behavior as the response of the magmatic system to variable influx of magma and gas at depth, increased flux at depth causing more frequent and stronger explosions at the surface. This relationship entails concurrent control of source processes over explosion frequency and intensity, directly impacting modeling of explosion sources at persistently active volcanoes in general and hazard assessment at Stromboli in particular.
    Description: DPC-INGV Project V2 “Paroxysm”
    Description: Published
    Description: 1–5
    Description: 3V. Dinamiche e scenari eruttivi
    Description: JCR Journal
    Description: reserved
    Keywords: Stromboli ; Strombolian frequency ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 22
    Publication Date: 2023-01-19
    Description: In situ measurements have been the basis for monitoring volcanic gas emissions for many years and—being complemented by remote sensing techniques—still play an important role to date. Concerning in situ techniques for sampling a dilute plume, an increase in accuracy and a reduction of detection limits are still necessary for most gases (e.g., CO2, SO2, HCl, HF, HBr, HI). In this work, the Raschig-Tube technique (RT) is modified and utilized for application on volcanic plumes. The theoretical and experimental absorption properties of the RT and the Drechsel bottle (DB) setups are characterized and both are applied simultaneously to the well-established Filter packs technique (FP) in the field (on Stromboli Island and Mount Etna). The comparison points out that FPs are the most practical to apply but the results are errorprone compared to RT and DB, whereas the RT results in up to 13 times higher analyte concentrations than the DB in the same sampling time. An optimization of the analytical procedure, including sample pretreatment and analysis by titration, Ion Chromatography, and Inductively Coupled Plasma Mass Spectrometry, led to a comprehensive data set covering a wide range of compounds. In particular, less abundant species were quantified more accurately and iodine was detected for the first time in Stromboli’s plume. Simultaneously applying Multiaxis Differential Optical Absorption Spectroscopy (MAX-DOAS) the chemical transformation of emitted bromide into bromine monoxide (BrO) from Stromboli and Etna was determined to 3–6% and 7%, respectively, within less than 5 min after the gas release from the active vents.
    Description: Published
    Description: 2797–2820
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: JCR Journal
    Description: restricted
    Keywords: plume ; volcano ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 23
    Publication Date: 2015-09-19
    Description: Sequence alignment is a long standing problem in bioinformatics. The Basic Local Alignment Search Tool (BLAST) is one of the most popular and fundamental alignment tools. The explosive growth of biological sequences calls for speedup of sequence alignment tools such as BLAST. To this end, we develop high speed BLASTN (HS-BLASTN), a parallel and fast nucleotide database search tool that accelerates MegaBLAST—the default module of NCBI-BLASTN. HS-BLASTN builds a new lookup table using the FMD-index of the database and employs an accurate and effective seeding method to find short stretches of identities (called seeds) between the query and the database. HS-BLASTN produces the same alignment results as MegaBLAST and its computational speed is much faster than MegaBLAST. Specifically, our experiments conducted on a 12-core server show that HS-BLASTN can be 22 times faster than MegaBLAST and exhibits better parallel performance than MegaBLAST. HS-BLASTN is written in C++ and the related source code is available at https://github.com/chenying2016/queries under the GPLv3 license.
    Keywords: Computational Methods
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  • 24
    Publication Date: 2015-05-29
    Description: Model evaluation is a necessary step for better prediction and design of 3D RNA structures. For proteins, this has been widely studied and the knowledge-based statistical potential has been proved to be one of effective ways to solve this problem. Currently, a few knowledge-based statistical potentials have also been proposed to evaluate predicted models of RNA tertiary structures. The benchmark tests showed that they can identify the native structures effectively but further improvements are needed to identify near-native structures and those with non-canonical base pairs. Here, we present a novel knowledge-based potential, 3dRNAscore, which combines distance-dependent and dihedral-dependent energies. The benchmarks on different testing datasets all show that 3dRNAscore are more efficient than existing evaluation methods in recognizing native state from a pool of near-native states of RNAs as well as in ranking near-native states of RNA models.
    Keywords: Computational Methods
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  • 25
    Publication Date: 2016-06-21
    Description: The goal of pathway analysis is to identify the pathways that are significantly impacted when a biological system is perturbed, e.g. by a disease or drug. Current methods treat pathways as independent entities. However, many signals are constantly sent from one pathway to another, essentially linking all pathways into a global, system-wide complex. In this work, we propose a set of three pathway analysis methods based on the impact analysis, that performs a system-level analysis by considering all signals between pathways, as well as their overlaps. Briefly, the global system is modeled in two ways: (i) considering the inter-pathway interaction exchange for each individual pathways, and (ii) combining all individual pathways to form a global, system-wide graph. The third analysis method is a hybrid of these two models. The new methods were compared with DAVID, GSEA, GSA, PathNet, Crosstalk and SPIA on 23 GEO data sets involving 19 tissues investigated in 12 conditions. The results show that both the ranking and the P -values of the target pathways are substantially improved when the analysis considers the system-wide dependencies and interactions between pathways.
    Keywords: Computational Methods
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  • 26
    Publication Date: 2016-07-09
    Description: Bioinformatic analysis often produces large sets of genomic ranges that can be difficult to interpret in the absence of genomic context. Goldmine annotates genomic ranges from any source with gene model and feature contexts to facilitate global descriptions and candidate loci discovery. We demonstrate the value of genomic context by using Goldmine to elucidate context dynamics in transcription factor binding and to reveal differentially methylated regions (DMRs) with context-specific functional correlations. The open source R package and documentation for Goldmine are available at http://jeffbhasin.github.io/goldmine .
    Keywords: Computational Methods
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  • 27
    Publication Date: 2016-07-28
    Description: CCCTC-binding factor (CTCF) is a multi-functional protein that is assigned various, even contradictory roles in the genome. High-throughput sequencing-based technologies such as ChIP-seq and Hi-C provided us the opportunity to assess the multivalent functions of CTCF in the human genome. The location of CTCF-binding sites with respect to genomic features provides insights into the possible roles of this protein. Here we present the first genome-wide survey and characterization of three important functions of CTCF: enhancer insulator, chromatin barrier and enhancer linker. We developed a novel computational framework to discover the multivalent functions of CTCF based on chromatin state and three-dimensional chromatin architecture. We applied our method to five human cell lines and identified ~46 000 non-redundant CTCF sites related to the three functions. Disparate effects of these functions on gene expression were found and distinct genomic features of these CTCF sites were characterized in GM12878 cells. Finally, we investigated the cell-type specificities of CTCF sites related to these functions across five cell types. Our study provides new insights into the multivalent functions of CTCF in the human genome.
    Keywords: Computational Methods
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  • 28
    Publication Date: 2015-05-03
    Description: MicroRNAs (miRNAs) regulate gene expression by binding to partially complementary sequences on target mRNA transcripts, thereby causing their degradation, deadenylation, or inhibiting their translation. Genomic variants can alter miRNA regulation by modifying miRNA target sites, and multiple human disease phenotypes have been linked to such miRNA target site variants (miR-TSVs). However, systematic genome-wide identification of functional miR-TSVs is difficult due to high false positive rates; functional miRNA recognition sequences can be as short as six nucleotides, with the human genome encoding thousands of miRNAs. Furthermore, while large-scale clinical genomic data sets are becoming increasingly commonplace, existing miR-TSV prediction methods are not designed to analyze these data. Here, we present an open-source tool called SubmiRine that is designed to perform efficient miR-TSV prediction systematically on variants identified in novel clinical genomic data sets. Most importantly, SubmiRine allows for the prioritization of predicted miR-TSVs according to their relative probability of being functional. We present the results of SubmiRine using integrated clinical genomic data from a large-scale cohort study on chronic obstructive pulmonary disease (COPD), making a number of high-scoring, novel miR-TSV predictions. We also demonstrate SubmiRine's ability to predict and prioritize known miR-TSVs that have undergone experimental validation in previous studies.
    Keywords: Computational Methods
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  • 29
    Publication Date: 2015-01-24
    Description: Of the ~1.3 million Alu elements in the human genome, only a tiny number are estimated to be active in transcription by RNA polymerase (Pol) III. Tracing the individual loci from which Alu transcripts originate is complicated by their highly repetitive nature. By exploiting RNA-Seq data sets and unique Alu DNA sequences, we devised a bioinformatic pipeline allowing us to identify Pol III-dependent transcripts of individual Alu elements. When applied to ENCODE transcriptomes of seven human cell lines, this search strategy identified ~1300 Alu loci corresponding to detectable transcripts, with ~120 of them expressed in at least three cell lines. In vitro transcription of selected Alu s did not reflect their in vivo expression properties, and required the native 5'-flanking region in addition to internal promoter. We also identified a cluster of expressed Alu Ya5-derived transcription units, juxtaposed to snaR genes on chromosome 19, formed by a promoter-containing left monomer fused to an Alu -unrelated downstream moiety. Autonomous Pol III transcription was also revealed for Alu s nested within Pol II-transcribed genes. The ability to investigate Alu transcriptomes at single-locus resolution will facilitate both the identification of novel biologically relevant Alu RNAs and the assessment of Alu expression alteration under pathological conditions.
    Keywords: Computational Methods
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  • 30
    Publication Date: 2016-04-08
    Description: Existing methods for interpreting protein variation focus on annotating mutation pathogenicity rather than detailed interpretation of variant deleteriousness and frequently use only sequence-based or structure-based information. We present VIPUR, a computational framework that seamlessly integrates sequence analysis and structural modelling (using the Rosetta protein modelling suite) to identify and interpret deleterious protein variants. To train VIPUR, we collected 9477 protein variants with known effects on protein function from multiple organisms and curated structural models for each variant from crystal structures and homology models. VIPUR can be applied to mutations in any organism's proteome with improved generalized accuracy (AUROC .83) and interpretability (AUPR .87) compared to other methods. We demonstrate that VIPUR's predictions of deleteriousness match the biological phenotypes in ClinVar and provide a clear ranking of prediction confidence. We use VIPUR to interpret known mutations associated with inflammation and diabetes, demonstrating the structural diversity of disrupted functional sites and improved interpretation of mutations associated with human diseases. Lastly, we demonstrate VIPUR's ability to highlight candidate variants associated with human diseases by applying VIPUR to de novo variants associated with autism spectrum disorders.
    Keywords: Computational Methods
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  • 31
    Publication Date: 2015-10-15
    Description: Intrinsically disordered proteins and regions (IDPs and IDRs) lack stable 3D structure under physiological conditions in-vitro , are common in eukaryotes, and facilitate interactions with RNA, DNA and proteins. Current methods for prediction of IDPs and IDRs do not provide insights into their functions, except for a handful of methods that address predictions of protein-binding regions. We report first-of-its-kind computational method DisoRDPbind for high-throughput prediction of RNA, DNA and protein binding residues located in IDRs from protein sequences. DisoRDPbind is implemented using a runtime-efficient multi-layered design that utilizes information extracted from physiochemical properties of amino acids, sequence complexity, putative secondary structure and disorder and sequence alignment. Empirical tests demonstrate that it provides accurate predictions that are competitive with other predictors of disorder-mediated protein binding regions and complementary to the methods that predict RNA- and DNA-binding residues annotated based on crystal structures. Application in Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila melanogaster proteomes reveals that RNA- and DNA-binding proteins predicted by DisoRDPbind complement and overlap with the corresponding known binding proteins collected from several sources. Also, the number of the putative protein-binding regions predicted with DisoRDPbind correlates with the promiscuity of proteins in the corresponding protein–protein interaction networks. Webserver: http://biomine.ece.ualberta.ca/DisoRDPbind/
    Keywords: Computational Methods
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  • 32
    Publication Date: 2016-06-03
    Description: The sequential chain of interactions altering the binary state of a biomolecule represents the ‘information flow’ within a cellular network that determines phenotypic properties. Given the lack of computational tools to dissect context-dependent networks and gene activities, we developed NetDecoder, a network biology platform that models context-dependent information flows using pairwise phenotypic comparative analyses of protein–protein interactions. Using breast cancer, dyslipidemia and Alzheimer's disease as case studies, we demonstrate NetDecoder dissects subnetworks to identify key players significantly impacting cell behaviour specific to a given disease context. We further show genes residing in disease-specific subnetworks are enriched in disease-related signalling pathways and information flow profiles, which drive the resulting disease phenotypes. We also devise a novel scoring scheme to quantify key genes—network routers, which influence many genes, key targets, which are influenced by many genes, and high impact genes, which experience a significant change in regulation. We show the robustness of our results against parameter changes. Our network biology platform includes freely available source code ( http://www.NetDecoder.org ) for researchers to explore genome-wide context-dependent information flow profiles and key genes, given a set of genes of particular interest and transcriptome data. More importantly, NetDecoder will enable researchers to uncover context-dependent drug targets.
    Keywords: Computational Methods
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  • 33
    Publication Date: 2015-04-21
    Description: limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
    Keywords: Computational Methods
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  • 34
    Publication Date: 2015-02-18
    Description: Protein sequences predicted from metagenomic datasets are annotated by identifying their homologs via sequence comparisons with reference or curated proteins. However, a majority of metagenomic protein sequences are partial-length, arising as a result of identifying genes on sequencing reads or on assembled nucleotide contigs, which themselves are often very fragmented. The fragmented nature of metagenomic protein predictions adversely impacts homology detection and, therefore, the quality of the overall annotation of the dataset. Here we present a novel algorithm called GRASP that accurately identifies the homologs of a given reference protein sequence from a database consisting of partial-length metagenomic proteins. Our homology detection strategy is guided by the reference sequence, and involves the simultaneous search and assembly of overlapping database sequences. GRASP was compared to three commonly used protein sequence search programs (BLASTP, PSI-BLAST and FASTM). Our evaluations using several simulated and real datasets show that GRASP has a significantly higher sensitivity than these programs while maintaining a very high specificity. GRASP can be a very useful program for detecting and quantifying taxonomic and protein family abundances in metagenomic datasets. GRASP is implemented in GNU C++, and is freely available at http://sourceforge.net/projects/grasp-release .
    Keywords: Computational Methods
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  • 35
    Publication Date: 2015-02-18
    Description: Genetic screens of an unprecedented scale have recently been made possible by the availability of high-complexity libraries of synthetic oligonucleotides designed to mediate either gene knockdown or gene knockout, coupled with next-generation sequencing. However, several sources of random noise and statistical biases complicate the interpretation of the resulting high-throughput data. We developed HiTSelect, a comprehensive analysis pipeline for rigorously selecting screen hits and identifying functionally relevant genes and pathways by addressing off-target effects, controlling for variance in both gene silencing efficiency and sequencing depth of coverage and integrating relevant metadata. We document the superior performance of HiTSelect using data from both genome-wide RNAi and CRISPR/Cas9 screens. HiTSelect is implemented as an open-source package, with a user-friendly interface for data visualization and pathway exploration. Binary executables are available at http://sourceforge.net/projects/hitselect/ , and the source code is available at https://github.com/diazlab/HiTSelect .
    Keywords: Computational Methods
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  • 36
    Publication Date: 2015-01-24
    Description: Integrative analyses of epigenetic data promise a deeper understanding of the epigenome. Epidaurus is a bioinformatics tool used to effectively reveal inter-dataset relevance and differences through data aggregation, integration and visualization. In this study, we demonstrated the utility of Epidaurus in validating hypotheses and generating novel biological insights. In particular, we described the use of Epidaurus to (i) integrate epigenetic data from prostate cancer cell lines to validate the activation function of EZH2 in castration-resistant prostate cancer and to (ii) study the mechanism of androgen receptor ( AR ) binding deregulation induced by the knockdown of FOXA1 . We found that EZH2 's noncanonical activation function was reaffirmed by its association with active histone markers and the lack of association with repressive markers. More importantly, we revealed that the binding of AR was selectively reprogramed to promoter regions, leading to the up-regulation of hundreds of cancer-associated genes including EGFR . The prebuilt epigenetic dataset from commonly used cell lines (LNCaP, VCaP, LNCaP-Abl, MCF7, GM12878, K562, HeLa-S3, A549, HePG2) makes Epidaurus a useful online resource for epigenetic research. As standalone software, Epidaurus is specifically designed to process user customized datasets with both efficiency and convenience.
    Keywords: Computational Methods
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  • 37
    Publication Date: 2015-02-18
    Description: RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization. In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation. The experimental methods to solve RNA-protein interaction prediction problem remain expensive and time-consuming. Here, we present the RPI-Pred (RNA-protein interaction predictor), a new support-vector machine-based method, to predict protein-RNA interaction pairs, based on both the sequences and structures. The results show that RPI-Pred can correctly predict RNA-protein interaction pairs with ~94% prediction accuracy when using sequence and experimentally determined protein and RNA structures, and with ~83% when using sequences and predicted protein and RNA structures. Further, our proposed method RPI-Pred was superior to other existing ones by predicting more experimentally validated ncRNA-protein interaction pairs from different organisms. Motivated by the improved performance of RPI-Pred, we further applied our method for reliable construction of ncRNA-protein interaction networks. The RPI-Pred is publicly available at: http://ctsb.is.wfubmc.edu/projects/rpi-pred .
    Keywords: Computational Methods
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  • 38
    Publication Date: 2015-02-18
    Description: Identifying conserved and divergent response patterns in gene networks is becoming increasingly important. A common approach is integrating expression information with gene association networks in order to find groups of connected genes that are activated or repressed. In many cases, researchers are also interested in comparisons across species (or conditions). Finding an active sub-network is a hard problem and applying it across species requires further considerations (e.g. orthology information, expression data and networks from different sources). To address these challenges we devised ModuleBlast, which uses both expression and network topology to search for highly relevant sub-networks. We have applied ModuleBlast to expression and interaction data from mouse, macaque and human to study immune response and aging. The immune response analysis identified several relevant modules, consistent with recent findings on apoptosis and NFB activation following infection. Temporal analysis of these data revealed cascades of modules that are dynamically activated within and across species. We have experimentally validated some of the novel hypotheses resulting from the analysis of the ModuleBlast results leading to new insights into the mechanisms used by a key mammalian aging protein.
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  • 39
    Publication Date: 2015-02-18
    Description: Here we used discriminative training methods to uncover the chromatin, transcription factor (TF) binding and sequence features of enhancers underlying gene expression in individual cardiac cells. We used machine learning with TF motifs and ChIP data for a core set of cardiogenic TFs and histone modifications to classify Drosophila cell-type-specific cardiac enhancer activity. We show that the classifier models can be used to predict cardiac cell subtype cis -regulatory activities. Associating the predicted enhancers with an expression atlas of cardiac genes further uncovered clusters of genes with transcription and function limited to individual cardiac cell subtypes. Further, the cell-specific enhancer models revealed chromatin, TF binding and sequence features that distinguish enhancer activities in distinct subsets of heart cells. Collectively, our results show that computational modeling combined with empirical testing provides a powerful platform to uncover the enhancers, TF motifs and gene expression profiles which characterize individual cardiac cell fates.
    Keywords: Computational Methods
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  • 40
    Publication Date: 2015-09-30
    Description: A key aspect of RNA secondary structure prediction is the identification of novel functional elements. This is a challenging task because these elements typically are embedded in longer transcripts where the borders between the element and flanking regions have to be defined. The flanking sequences impact the folding of the functional elements both at the level of computational analyses and when the element is extracted as a transcript for experimental analysis. Here, we analyze how different flanking region lengths impact folding into a constrained structure by computing probabilities of folding for different sizes of flanking regions. Our method, RNAcop (RNA context optimization by probability), is tested on known and de novo predicted structures. In vitro experiments support the computational analysis and suggest that for a number of structures, choosing proper lengths of flanking regions is critical. RNAcop is available as web server and stand-alone software via http://rth.dk/resources/rnacop .
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  • 41
    Publication Date: 2016-03-01
    Description: It is being increasingly realized that nucleosome organization on DNA crucially regulates DNA–protein interactions and the resulting gene expression. While the spatial character of the nucleosome positioning on DNA has been experimentally and theoretically studied extensively, the temporal character is poorly understood. Accounting for ATPase activity and DNA-sequence effects on nucleosome kinetics, we develop a theoretical method to estimate the time of continuous exposure of binding sites of non-histone proteins (e.g. transcription factors and TATA binding proteins) along any genome. Applying the method to Saccharomyces cerevisiae , we show that the exposure timescales are determined by cooperative dynamics of multiple nucleosomes, and their behavior is often different from expectations based on static nucleosome occupancy. Examining exposure times in the promoters of GAL1 and PHO5, we show that our theoretical predictions are consistent with known experiments. We apply our method genome-wide and discover huge gene-to-gene variability of mean exposure times of TATA boxes and patches adjacent to TSS (+1 nucleosome region); the resulting timescale distributions have non-exponential tails.
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  • 42
    Publication Date: 2015-10-31
    Description: Systems biologists aim to decipher the structure and dynamics of signaling and regulatory networks underpinning cellular responses; synthetic biologists can use this insight to alter existing networks or engineer de novo ones. Both tasks will benefit from an understanding of which structural and dynamic features of networks can emerge from evolutionary processes, through which intermediary steps these arise, and whether they embody general design principles. As natural evolution at the level of network dynamics is difficult to study, in silico evolution of network models can provide important insights. However, current tools used for in silico evolution of network dynamics are limited to ad hoc computer simulations and models. Here we introduce BioJazz, an extendable, user-friendly tool for simulating the evolution of dynamic biochemical networks. Unlike previous tools for in silico evolution, BioJazz allows for the evolution of cellular networks with unbounded complexity by combining rule-based modeling with an encoding of networks that is akin to a genome. We show that BioJazz can be used to implement biologically realistic selective pressures and allows exploration of the space of network architectures and dynamics that implement prescribed physiological functions. BioJazz is provided as an open-source tool to facilitate its further development and use. Source code and user manuals are available at: http://oss-lab.github.io/biojazz and http://osslab.lifesci.warwick.ac.uk/BioJazz.aspx .
    Keywords: Computational Methods
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  • 43
    Publication Date: 2015-12-02
    Description: Despite the biological importance of non-coding RNA, their structural characterization remains challenging. Making use of the rapidly growing sequence databases, we analyze nucleotide coevolution across homologous sequences via Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a representative set of riboswitches, we show that the results of Direct-Coupling Analysis in combination with a generalized Nussinov algorithm systematically improve the results of RNA secondary structure prediction beyond traditional covariance approaches based on mutual information. Even more importantly, we show that the results of Direct-Coupling Analysis are enriched in tertiary structure contacts. By integrating these predictions into molecular modeling tools, systematically improved tertiary structure predictions can be obtained, as compared to using secondary structure information alone.
    Keywords: Computational Methods
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  • 44
    Publication Date: 2015-12-02
    Description: Sequence variations in regulatory DNA regions are known to cause functionally important consequences for gene expression. DNA sequence variations may have an essential role in determining phenotypes and may be linked to disease; however, their identification through analysis of massive genome-wide sequencing data is a great challenge. In this work, a new computational pipeline, a Bayesian method for protein–DNA interaction with binding affinity ranking (BayesPI-BAR), is proposed for quantifying the effect of sequence variations on protein binding. BayesPI-BAR uses biophysical modeling of protein–DNA interactions to predict single nucleotide polymorphisms (SNPs) that cause significant changes in the binding affinity of a regulatory region for transcription factors (TFs). The method includes two new parameters (TF chemical potentials or protein concentrations and direct TF binding targets) that are neglected by previous methods. The new method is verified on 67 known human regulatory SNPs, of which 47 (70%) have predicted true TFs ranked in the top 10. Importantly, the performance of BayesPI-BAR, which uses principal component analysis to integrate multiple predictions from various TF chemical potentials, is found to be better than that of existing programs, such as sTRAP and is-rSNP, when evaluated on the same SNPs. BayesPI-BAR is a publicly available tool and is able to carry out parallelized computation, which helps to investigate a large number of TFs or SNPs and to detect disease-associated regulatory sequence variations in the sea of genome-wide noncoding regions.
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  • 45
    Publication Date: 2015-03-14
    Description: The rapid discovery of potential driver mutations through large-scale mutational analyses of human cancers generates a need to characterize their cellular phenotypes. Among the techniques for genome editing, recombinant adeno-associated virus (rAAV)-mediated gene targeting is suited for knock-in of single nucleotide substitutions and to a lesser degree for gene knock-outs. However, the generation of gene targeting constructs and the targeting process is time-consuming and labor-intense. To facilitate rAAV-mediated gene targeting, we developed the first software and complementary automation-friendly vector tools to generate optimized targeting constructs for editing human protein encoding genes. By computational approaches, rAAV constructs for editing ~71% of bases in protein-coding exons were designed. Similarly, ~81% of genes were predicted to be targetable by rAAV-mediated knock-out. A Gateway-based cloning system for facile generation of rAAV constructs suitable for robotic automation was developed and used in successful generation of targeting constructs. Together, these tools enable automated rAAV targeting construct design, generation as well as enrichment and expansion of targeted cells with desired integrations.
    Keywords: Computational Methods
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  • 46
    Publication Date: 2015-03-14
    Description: Degenerate codon (DC) libraries efficiently address the experimental library-size limitations of directed evolution by focusing diversity toward the positions and toward the amino acids (AAs) that are most likely to generate hits; however, manually constructing DC libraries is challenging, error prone and time consuming. This paper provides a dynamic programming solution to the task of finding the best DCs while keeping the size of the library beneath some given limit, improving on the existing integer-linear programming formulation. It then extends the algorithm to consider multiple DCs at each position, a heretofore unsolved problem, while adhering to a constraint on the number of primers needed to synthesize the library. In the two library-design problems examined here, the use of multiple DCs produces libraries that very nearly cover the set of desired AAs while still staying within the experimental size limits. Surprisingly, the algorithm is able to find near-perfect libraries where the ratio of amino-acid sequences to nucleic-acid sequences approaches 1; it effectively side-steps the degeneracy of the genetic code. Our algorithm is freely available through our web server and solves most design problems in about a second.
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  • 47
    Publication Date: 2015-01-10
    Description: Transcription regulation in multicellular eukaryotes is orchestrated by a number of DNA functional elements located at gene regulatory regions. Some regulatory regions (e.g. enhancers) are located far away from the gene they affect. Identification of distal regulatory elements is a challenge for the bioinformatics research. Although existing methodologies increased the number of computationally predicted enhancers, performance inconsistency of computational models across different cell-lines, class imbalance within the learning sets and ad hoc rules for selecting enhancer candidates for supervised learning, are some key questions that require further examination. In this study we developed DEEP, a novel ensemble prediction framework. DEEP integrates three components with diverse characteristics that streamline the analysis of enhancer's properties in a great variety of cellular conditions. In our method we train many individual classification models that we combine to classify DNA regions as enhancers or non-enhancers. DEEP uses features derived from histone modification marks or attributes coming from sequence characteristics. Experimental results indicate that DEEP performs better than four state-of-the-art methods on the ENCODE data. We report the first computational enhancer prediction results on FANTOM5 data where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and sensitivity across 36 different tissues. We further present results derived using in vivo -derived enhancer data from VISTA database. DEEP-VISTA, when tested on an independent test set, achieved GM of 80.1% and accuracy of 89.64%. DEEP framework is publicly available at http://cbrc.kaust.edu.sa/deep/ .
    Keywords: Computational Methods
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  • 48
    Publication Date: 2016-03-19
    Description: The yeast mutant collections are a fundamental tool in deciphering genomic organization and function. Over the last decade, they have been used for the systematic exploration of ~6 000 000 double gene mutants, identifying and cataloging genetic interactions among them. Here we studied the extent to which these data are prone to neighboring gene effects (NGEs), a phenomenon by which the deletion of a gene affects the expression of adjacent genes along the genome. Analyzing ~90,000 negative genetic interactions observed to date, we found that more than 10% of them are incorrectly annotated due to NGEs. We developed a novel algorithm, GINGER, to identify and correct erroneous interaction annotations. We validated the algorithm using a comparative analysis of interactions from Schizosaccharomyces pombe . We further showed that our predictions are significantly more concordant with diverse biological data compared to their mis-annotated counterparts. Our work uncovered about 9500 new genetic interactions in yeast.
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  • 49
    Publication Date: 2016-03-19
    Description: Transfer RNAs (tRNAs) are essential for encoding the transcribed genetic information from DNA into proteins. Variations in the human tRNAs are involved in diverse clinical phenotypes. Interestingly, all pathogenic variations in tRNAs are located in mitochondrial tRNAs (mt-tRNAs). Therefore, it is crucial to identify pathogenic variations in mt-tRNAs for disease diagnosis and proper treatment. We collected mt-tRNA variations using a classification based on evidence from several sources and used the data to develop a multifactorial probability-based prediction method, PON-mt-tRNA, for classification of mt-tRNA single nucleotide substitutions. We integrated a machine learning-based predictor and an evidence-based likelihood ratio for pathogenicity using evidence of segregation, biochemistry and histochemistry to predict the posterior probability of pathogenicity of variants. The accuracy and Matthews correlation coefficient (MCC) of PON-mt-tRNA are 1.00 and 0.99, respectively. In the absence of evidence from segregation, biochemistry and histochemistry, PON-mt-tRNA classifies variations based on the machine learning method with an accuracy and MCC of 0.69 and 0.39, respectively. We classified all possible single nucleotide substitutions in all human mt-tRNAs using PON-mt-tRNA. The variations in the loops are more often tolerated compared to the variations in stems. The anticodon loop contains comparatively more predicted pathogenic variations than the other loops. PON-mt-tRNA is available at http://structure.bmc.lu.se/PON-mt-tRNA/ .
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  • 50
    Publication Date: 2016-05-06
    Description: Sequence Logos and its variants are the most commonly used method for visualization of multiple sequence alignments (MSAs) and sequence motifs. They provide consensus-based summaries of the sequences in the alignment. Consequently, individual sequences cannot be identified in the visualization and covariant sites are not easily discernible. We recently proposed Sequence Bundles , a motif visualization technique that maintains a one-to-one relationship between sequences and their graphical representation and visualizes covariant sites. We here present Alvis, an open-source platform for the joint explorative analysis of MSAs and phylogenetic trees, employing Sequence Bundles as its main visualization method. Alvis combines the power of the visualization method with an interactive toolkit allowing detection of covariant sites, annotation of trees with synapomorphies and homoplasies, and motif detection. It also offers numerical analysis functionality, such as dimension reduction and classification. Alvis is user-friendly, highly customizable and can export results in publication-quality figures. It is available as a full-featured standalone version ( http://www.bitbucket.org/rfs/alvis ) and its Sequence Bundles visualization module is further available as a web application ( http://science-practice.com/projects/sequence-bundles ).
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  • 51
    Publication Date: 2016-10-14
    Description: Functional RNA regions are often related to recurrent secondary structure patterns (or motifs), which can exert their role in several different ways, particularly in dictating the interaction with RNA-binding proteins, and acting in the regulation of a large number of cellular processes. Among the available motif-finding tools, the majority focuses on sequence patterns, sometimes including secondary structure as additional constraints to improve their performance. Nonetheless, secondary structures motifs may be concurrent to their sequence counterparts or even encode a stronger functional signal. Current methods for searching structural motifs generally require long pipelines and/or high computational efforts or previously aligned sequences. Here, we present BEAM (BEAr Motif finder), a novel method for structural motif discovery from a set of unaligned RNAs, taking advantage of a recently developed encoding for RNA secondary structure named BEAR (Brand nEw Alphabet for RNAs) and of evolutionary substitution rates of secondary structure elements. Tested in a varied set of scenarios, from small- to large-scale, BEAM is successful in retrieving structural motifs even in highly noisy data sets, such as those that can arise in CLIP-Seq or other high-throughput experiments.
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  • 52
    Publication Date: 2016-12-01
    Description: Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish ( Danio rerio ), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet ( www.inetbio.org/danionet ), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery.
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  • 53
    Publication Date: 2016-12-04
    Description: Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype–genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank, we find that frustration produces many immediately intuitive results: for instance, disease-related SNVs create stronger changes in localized frustration than non-disease related variants, and rare SNVs tend to disrupt local interactions to a larger extent than common variants. Less obviously, we observe that somatic SNVs associated with oncogenes and tumor suppressor genes (TSGs) induce very different changes in frustration. In particular, those associated with TSGs change the frustration more in the core than the surface (by introducing loss-of-function events), whereas those associated with oncogenes manifest the opposite pattern, creating gain-of-function events.
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  • 54
    Publication Date: 2016-12-17
    Description: A complex disease generally results not from malfunction of individual molecules but from dysfunction of the relevant system or network, which dynamically changes with time and conditions. Thus, estimating a condition-specific network from a single sample is crucial to elucidating the molecular mechanisms of complex diseases at the system level. However, there is currently no effective way to construct such an individual-specific network by expression profiling of a single sample because of the requirement of multiple samples for computing correlations. We developed here with a statistical method, i.e. a sample-specific network (SSN) method, which allows us to construct individual-specific networks based on molecular expressions of a single sample. Using this method, we can characterize various human diseases at a network level. In particular, such SSNs can lead to the identification of individual-specific disease modules as well as driver genes, even without gene sequencing information. Extensive analysis by using the Cancer Genome Atlas data not only demonstrated the effectiveness of the method, but also found new individual-specific driver genes and network patterns for various types of cancer. Biological experiments on drug resistance further validated one important advantage of our method over the traditional methods, i.e. we can even identify such drug resistance genes that actually have no clear differential expression between samples with and without the resistance, due to the additional network information.
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  • 55
    Publication Date: 2016-12-17
    Description: Motivation: Many biological processes, such as cell cycle, circadian clock, menstrual cycles, are governed by oscillatory systems consisting of numerous components that exhibit rhythmic patterns over time. It is not always easy to identify such rhythmic components. For example, it is a challenging problem to identify circadian genes in a given tissue using time-course gene expression data. There is a great potential for misclassifying non-rhythmic as rhythmic genes and vice versa. This has been a problem of considerable interest in recent years. In this article we develop a constrained inference based methodology called Order Restricted Inference for Oscillatory Systems (ORIOS) to detect rhythmic signals. Instead of using mathematical functions (e.g. sinusoidal) to describe shape of rhythmic signals, ORIOS uses mathematical inequalities. Consequently, it is robust and not limited by the biologist's choice of the mathematical model. We studied the performance of ORIOS using simulated as well as real data obtained from mouse liver, pituitary gland and data from NIH3T3, U2OS cell lines. Our results suggest that, for a broad collection of patterns of gene expression, ORIOS has substantially higher power to detect true rhythmic genes in comparison to some popular methods, while also declaring substantially fewer non-rhythmic genes as rhythmic. Availability and Implementation: A user friendly code implemented in R language can be downloaded from http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/peddada/index.cfm . Contact: peddada@niehs.nih.gov
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  • 56
    Publication Date: 2015-11-17
    Description: Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation and metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates of known metabolites increasingly frustrate conventional natural product screening programs. New methods to connect biosynthetic gene clusters to novel chemical scaffolds are therefore critical to enable the targeted discovery of genetically encoded natural products. Here, we present PRISM, a computational resource for the identification of biosynthetic gene clusters, prediction of genetically encoded nonribosomal peptides and type I and II polyketides, and bio- and cheminformatic dereplication of known natural products. PRISM implements novel algorithms which render it uniquely capable of predicting type II polyketides, deoxygenated sugars, and starter units, making it a comprehensive genome-guided chemical structure prediction engine. A library of 57 tailoring reactions is leveraged for combinatorial scaffold library generation when multiple potential substrates are consistent with biosynthetic logic. We compare the accuracy of PRISM to existing genomic analysis platforms. PRISM is an open-source, user-friendly web application available at http://magarveylab.ca/prism/ .
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  • 57
    Publication Date: 2015-07-25
    Description: The cMonkey integrated biclustering algorithm identifies conditionally co-regulated modules of genes (biclusters). cMonkey integrates various orthogonal pieces of information which support evidence of gene co-regulation, and optimizes biclusters to be supported simultaneously by one or more of these prior constraints. The algorithm served as the cornerstone for constructing the first global, predictive Environmental Gene Regulatory Influence Network (EGRIN) model for a free-living cell, and has now been applied to many more organisms. However, due to its computational inefficiencies, long run-time and complexity of various input data types, cMonkey was not readily usable by the wider community. To address these primary concerns, we have significantly updated the cMonkey algorithm and refactored its implementation, improving its usability and extendibility. These improvements provide a fully functioning and user-friendly platform for building co-regulated gene modules and the tools necessary for their exploration and interpretation. We show, via three separate analyses of data for E. coli, M. tuberculosis and H. sapiens , that the updated algorithm and inclusion of novel scoring functions for new data types (e.g. ChIP-seq and transcription factor over-expression [TFOE]) improve discovery of biologically informative co-regulated modules. The complete cMonkey 2 software package, including source code, is available at https://github.com/baliga-lab/cmonkey2 .
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  • 58
    Publication Date: 2017-01-10
    Description: RNA molecules are attractive therapeutic targets because non-coding RNA molecules have increasingly been found to play key regulatory roles in the cell. Comparing and classifying RNA 3D structures yields unique insights into RNA evolution and function. With the rapid increase in the number of atomic-resolution RNA structures, it is crucial to have effective tools to classify RNA structures and to investigate them for structural similarities at different resolutions. We previously developed the algorithm CLICK to superimpose a pair of protein 3D structures by clique matching and 3D least squares fitting. In this study, we extend and optimize the CLICK algorithm to superimpose pairs of RNA 3D structures and RNA–protein complexes, independent of the associated topologies. Benchmarking Rclick on four different datasets showed that it is either comparable to or better than other structural alignment methods in terms of the extent of structural overlaps. Rclick also recognizes conformational changes between RNA structures and produces complementary alignments to maximize the extent of detectable similarity. Applying Rclick to study Ribonuclease III protein correctly aligned the RNA binding sites of RNAse III with its substrate. Rclick can be further extended to identify ligand-binding pockets in RNA. A web server is developed at http://mspc.bii.a-star.edu.sg/minhn/rclick.html .
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