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  • Computational Methods, Genomics  (73)
  • Circulation/ Dynamics  (41)
  • Oxford University Press  (73)
  • American Meteorological Society  (41)
  • 2015-2019  (114)
  • 1995-1999
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  • 1
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2006–2024, doi:10.1175/JPO-D-14-0234.1.
    Description: The effects of wind-driven whitecapping on the evolution of the ocean surface boundary layer are examined using an idealized one-dimensional Reynolds-averaged Navier–Stokes numerical model. Whitecapping is parameterized as a flux of turbulent kinetic energy through the sea surface and through an adjustment of the turbulent length scale. Simulations begin with a two-layer configuration and use a wind that ramps to a steady stress. This study finds that the boundary layer begins to thicken sooner in simulations with whitecapping than without because whitecapping introduces energy to the base of the boundary layer sooner than shear production does. Even in the presence of whitecapping, shear production becomes important for several hours, but then inertial oscillations cause shear production and whitecapping to alternate as the dominant energy sources for mixing. Details of these results are sensitive to initial and forcing conditions, particularly to the turbulent length scale imposed by breaking waves and the transfer velocity of energy from waves to turbulence. After 1–2 days of steady wind, the boundary layer in whitecapping simulations has thickened more than the boundary layer in simulations without whitecapping by about 10%–50%, depending on the forcing and initial conditions.
    Description: We thank Skidmore College for financial and infrastructure support, and Skidmore and the National Science Foundation for funding travel to meetings where early versions of this work were presented. We also thank the National Science Foundation, Oregon State University, Jonathan Nash, and Joe Jurisa for funding and hosting a workshop on River Plume Mixing in October, 2013, where ideas and context for this paper were developed.
    Description: 2016-02-01
    Keywords: Circulation/ Dynamics ; Mixing ; Turbulence ; Wave breaking ; Wind stress ; Atm/Ocean Structure/ Phenomena ; Mixed layer
    Repository Name: Woods Hole Open Access Server
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  • 2
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 28 (2015): 8574–8584, doi:10.1175/JCLI-D-14-00809.1.
    Description: The subsurface ocean response to anthropogenic climate forcing remains poorly characterized. From the Coupled Model Intercomparison Project (CMIP), a robust response of the lower thermocline is identified, where the warming is considerably weaker in the subtropics than in the tropics and high latitudes. The lower thermocline change is inversely proportional to the thermocline depth in the present climatology. Ocean general circulation model (OGCM) experiments show that sea surface warming is the dominant forcing for the subtropical gyre change in contrast to natural variability for which wind dominates, and the ocean response is insensitive to the spatial pattern of surface warming. An analysis based on a ventilated thermocline model shows that the pattern of the lower thermocline change can be interpreted in terms of the dynamic response to the strengthened stratification and downward heat mixing. Consequently, the subtropical gyres become intensified at the surface but weakened in the lower thermcline, consistent with results from CMIP experiments.
    Description: The work was supported by the National Basic Research Program of China (2012CB955600), the National Natural Science Foundation of China (41125019, 41206021), and the U.S. National Science Foundation (AGS 1249145, 1305719).
    Description: 2016-05-01
    Keywords: Circulation/ Dynamics ; Ocean circulation ; Physical Meteorology and Climatology ; Climate change
    Repository Name: Woods Hole Open Access Server
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  • 3
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    American Meteorological Society
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 546–561, doi:10.1175/JPO-D-14-0082.1.
    Description: Model studies and observations in the Hudson River estuary indicate that frontogenesis occurs as a result of topographic forcing. Bottom fronts form just downstream of lateral constrictions, where the width of the estuary increases in the down-estuary (i.e., seaward) direction. The front forms during the last several hours of the ebb, when the combination of adverse pressure gradient in the expansion and baroclinicity cause a stagnation of near-bottom velocity. Frontogenesis is observed in two dynamical regimes: one in which the front develops at a transition from subcritical to supercritical flow and the other in which the flow is everywhere supercritical. The supercritical front formation appears to be associated with lateral flow separation. Both types of fronts are three-dimensional, with strong lateral gradients along the flanks of the channel. During spring tide conditions, the fronts dissipate during the flood, whereas during neap tides the fronts are advected landward during the flood. The zone of enhanced density gradient initiates frontogenesis at multiple constrictions along the estuary as it propagates landward more than 60 km during several days of neap tides. Frontogenesis and frontal propagation may thus be essential elements of the spring-to-neap transition to stratified conditions in partially mixed estuaries.
    Description: Support for this research was provided by NSF Grant OCE 0926427.
    Description: 2015-08-01
    Keywords: Circulation/ Dynamics ; Baroclinic flows ; Coastal flows ; Frontogenesis/frontolysis ; Fronts
    Repository Name: Woods Hole Open Access Server
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  • 4
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    American Meteorological Society
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 606–612, doi:10.1175/JPO-D-14-0221.1.
    Description: Mesoscale intrathermocline lenses are observed throughout the World Ocean and are commonly attributed to water mass anomalies advected from a distant origin. An alternative mechanism of local generation is offered herein, in which eddy–wind interaction can create lens-shaped disturbances in the thermocline. Numerical simulations illustrate how eddy–wind-driven upwelling in anticyclones can yield a convex lens reminiscent of a mode water eddy, whereas eddy–wind-driven downwelling in cyclones produces a concave lens that thins the mode water layer (a cyclonic “thinny”). Such transformations should be observable with long-term time series in the interiors of mesoscale eddies.
    Description: Support of this research by the National Science Foundation and National Aeronautics and Space Administration is gratefully acknowledged.
    Description: 2015-08-01
    Keywords: Circulation/ Dynamics ; Eddies ; Ekman pumping/transport ; Mesoscale processes ; Models and modeling ; Ocean models ; Primitive equations model
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  • 5
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 966–987, doi:10.1175/JPO-D-14-0110.1.
    Description: A key remaining challenge in oceanography is the understanding and parameterization of small-scale mixing. Evidence suggests that topographic features play a significant role in enhancing mixing in the Southern Ocean. This study uses 914 high-resolution hydrographic profiles from novel EM-APEX profiling floats to investigate turbulent mixing north of the Kerguelen Plateau, a major topographic feature in the Southern Ocean. A shear–strain finescale parameterization is applied to estimate diapycnal diffusivity in the upper 1600 m of the ocean. The indirect estimates of mixing match direct microstructure profiler observations made simultaneously. It is found that mixing intensities have strong spatial and temporal variability, ranging from O(10−6) to O(10−3) m2 s−1. This study identifies topographic roughness, current speed, and wind speed as the main factors controlling mixing intensity. Additionally, the authors find strong regional variability in mixing dynamics and enhanced mixing in the Antarctic Circumpolar Current frontal region. This enhanced mixing is attributed to dissipating internal waves generated by the interaction of the Antarctic Circumpolar Current and the topography of the Kerguelen Plateau. Extending the mixing observations from the Kerguelen region to the entire Southern Ocean, this study infers a large water mass transformation rate of 17 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) across the boundary of Antarctic Intermediate Water and Upper Circumpolar Deep Water in the Antarctic Circumpolar Current. This work suggests that the contribution of mixing to the Southern Ocean overturning circulation budget is particularly significant in fronts.
    Description: AM was supported by the joint CSIRO–University of Tasmania Quantitative Marine Science (QMS) program and the 2009 CSIRO Wealth from Ocean Flagship Collaborative Fund. BMS was supported by the Australian Climate Change Science Program, jointly funded by the Department of the Environment and CSIRO. KLPs salary support was provided by Woods Hole Oceanographic Institution bridge support funds.
    Description: 2015-10-01
    Keywords: Geographic location/entity ; Southern Ocean ; Circulation/ Dynamics ; Diapycnal mixing ; Fronts ; Ocean circulation ; Topographic effects ; Atm/Ocean Structure/ Phenomena ; Mixing
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  • 6
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 1610–1631, doi:10.1175/JPO-D-14-0047.1.
    Description: The use of a measure to diagnose submesoscale isopycnal diffusivity by determining the best match between observations of a tracer and simulations with varying small-scale diffusivities is tested. Specifically, the robustness of a “roughness” measure to discriminate between tracer fields experiencing different submesoscale isopycnal diffusivities and advected by scaled altimetric velocity fields is investigated. This measure is used to compare numerical simulations of the tracer released at a depth of about 1.5 km in the Pacific sector of the Southern Ocean during the Diapycnal and Isopycnal Mixing Experiment in the Southern Ocean (DIMES) field campaign with observations of the tracer taken on DIMES cruises. The authors find that simulations with an isopycnal diffusivity of ~20 m2 s−1 best match observations in the Pacific sector of the Antarctic Circumpolar Current (ACC), rising to ~20–50 m2 s−1 through Drake Passage, representing submesoscale processes and any mesoscale processes unresolved by the advecting altimetry fields. The roughness measure is demonstrated to be a statistically robust way to estimate a small-scale diffusivity when measurements are relatively sparse in space and time, although it does not work if there are too few measurements overall. The planning of tracer measurements during a cruise in order to maximize the robustness of the roughness measure is also considered. It is found that the robustness is increased if the spatial resolution of tracer measurements is increased with the time since tracer release.
    Description: We thank the U.K. Natural Environment Research Council and the U.S. National Science Foundation for funding the DIMES project.
    Description: 2015-12-01
    Keywords: Geographic location/entity ; Southern Ocean ; Circulation/ Dynamics ; Diffusion ; Physical Meteorology and Climatology ; Isopycnal mixing ; Observational techniques and algorithms ; Tracers ; Models and modeling ; Model comparison ; Tracers
    Repository Name: Woods Hole Open Access Server
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  • 7
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2598–2620, doi:10.1175/JPO-D-14-0249.1.
    Description: Through combining analytical arguments and numerical models, this study investigates the finite-amplitude meanders of shelfbreak fronts characterized by sloping isopycnals outcropping at both the surface and the shelfbreak bottom. The objective is to provide a formula for the meander length scale that can explain observed frontal length scale variability and also be verified with observations. Considering the frontal instability to be a mixture of barotropic and baroclinic instability, the derived along-shelf meander length scale formula is [b1/(1 + a1S1/2)]NH/f, where N is the buoyancy frequency; H is the depth of the front; f is the Coriolis parameter; S is the Burger number measuring the ratio of energy conversion associated with barotropic and baroclinic instability; and a1 and b1 are empirical constants. Initial growth rate of the frontal instability is formulated as [b2(1 + a1S1/2)/(1 + a2αS1/2)]NH/L, where α is the bottom slope at the foot of the front, and a2 and b2 are empirical constants. The formulas are verified using numerical sensitivity simulations, and fitting of the simulated and formulated results gives a1 = 2.69, b1 = 14.65, a2 = 5.1 × 103, and b2 = 6.2 × 10−2. The numerical simulations also show development of fast-growing frontal symmetric instability when the minimum initial potential vorticity is negative. Although frontal symmetric instability leads to faster development of barotropic and baroclinic instability at later times, it does not significantly influence the meander length scale. The derived meander length scale provides a framework for future studies of the influences of external forces on shelfbreak frontal circulation and cross-frontal exchange.
    Description: WGZ and GGG were supported by the National Science Foundation through Grant OCE-1129125.
    Description: 2016-04-01
    Keywords: Circulation/ Dynamics ; Instability ; Ocean circulation ; Topographic effects ; Atm/Ocean Structure/ Phenomena ; Fronts ; Models and modeling ; Numerical analysis/modeling
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  • 8
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    American Meteorological Society
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2820–2835, doi:10.1175/JPO-D-15-0101.1.
    Description: The response of a convective ocean basin to variations in atmospheric temperature is explored using numerical models and theory. The results indicate that the general behavior depends strongly on the frequency at which the atmosphere changes relative to the local response time to air–sea heat flux. For high-frequency forcing, the convective region in the basin interior is essentially one-dimensional and responds to the integrated local surface heat flux anomalies. For low-frequency forcing, eddy fluxes from the boundary current into the basin interior become important and act to suppress variability forced by the atmosphere. A theory is developed to quantify this time-dependent response and its influence on various oceanic quantities. The amplitude and phase of the temperature and salinity of the convective water mass, the meridional overturning circulation, the meridional heat flux, and the air–sea heat flux predicted by the theory compare well with that diagnosed from a series of numerical model calculations in both strongly eddying and weakly eddying regimes. Linearized analytic solutions provide direct estimates of each of these quantities and demonstrate their dependence on the nondimensional numbers that characterize the domain and atmospheric forcing. These results highlight the importance of mesoscale eddies in modulating the mean and time-dependent ocean response to atmospheric variability and provide a dynamical framework with which to connect ocean observations with changes in the atmosphere and surface heat flux.
    Description: This study was supported by the National Science Foundation under Grant OCE-1232389.
    Description: 2016-05-01
    Keywords: Circulation/ Dynamics ; Atmosphere-ocean interaction ; Deep convection ; Eddies ; Meridional overturning circulation
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  • 9
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2913–2932, doi:10.1175/JPO-D-14-0179.1.
    Description: The oceanic deep circulation is shared between concentrated deep western boundary currents (DWBCs) and broader interior pathways, a process that is sensitive to seafloor topography. This study investigates the spreading and deepening of Denmark Strait overflow water (DSOW) in the western subpolar North Atlantic using two ° eddy-resolving Atlantic simulations, including a passive tracer injected into the DSOW. The deepest layers of DSOW transit from a narrow DWBC in the southern Irminger Sea into widespread westward flow across the central Labrador Sea, which remerges along the Labrador coast. This abyssal circulation, in contrast to the upper levels of overflow water that remain as a boundary current, blankets the deep Labrador Sea with DSOW. Farther downstream after being steered around the abrupt topography of Orphan Knoll, DSOW again leaves the boundary, forming cyclonic recirculation cells in the deep Newfoundland basin. The deep recirculation, mostly driven by the meandering pathway of the upper North Atlantic Current, leads to accumulation of tracer offshore of Orphan Knoll, precisely where a local maximum of chlorofluorocarbon (CFC) inventory is observed. At Flemish Cap, eddy fluxes carry ~20% of the tracer transport from the boundary current into the interior. Potential vorticity is conserved as the flow of DSOW broadens at the transition from steep to less steep continental rise into the Labrador Sea, while around the abrupt topography of Orphan Knoll, potential vorticity is not conserved and the DSOW deepens significantly.
    Description: This work is supported by ONR Award N00014-09-1-0587, the NSF Physical Oceanography Program, and NASA Ocean Surface Topography Science Team Program.
    Description: 2016-06-01
    Keywords: Circulation/ Dynamics ; Abyssal circulation ; Boundary currents ; Ocean circulation ; Ocean dynamics ; Potential vorticity ; Topographic effects
    Repository Name: Woods Hole Open Access Server
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  • 10
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2735-2768, doi:10.1175/JPO-D-15-0134.1.
    Description: In Greenland’s glacial fjords, heat and freshwater are exchanged between glaciers and the ocean. Submarine melting of glaciers has been implicated as a potential trigger for recent glacier acceleration, and observations of ocean heat transport are increasingly being used to infer the submarine melt rates. The complete heat, salt, and mass budgets that underlie such methods, however, have been largely neglected. Here, a new framework for exploring glacial fjord budgets is developed. Building on estuarine studies of salt budgets, the heat, salt, and mass transports through the fjord are decomposed, and new equations for calculating freshwater fluxes from submarine meltwater and runoff are presented. This method is applied to moored records from Sermilik Fjord, near the terminus of Helheim Glacier, to evaluate the dominant balances in the fjord budgets and to estimate freshwater fluxes. Throughout the year, two different regimes are found. In the nonsummer months, advective transports are balanced by changes in heat/salt storage within their ability to measure; freshwater fluxes cannot be inferred as a residual. In the summer, a mean exchange flow emerges, consisting of inflowing Atlantic water and outflowing glacially modified water. This exchange transports heat toward the glacier and is primarily balanced by changes in storage and latent heat for melting ice. The total freshwater flux increases over the summer, reaching 1200 ± 700 m3 s−1 of runoff and 1500 ± 500 m3 s−1 of submarine meltwater from glaciers and icebergs in August. The methods and results highlight important components of fjord budgets, particularly the storage and barotropic terms, that have been not been appropriately considered in previous estimates of submarine melting.
    Description: The data collection and analysis was funded by NSF Grants ARC-0909373, OCE-113008, and OCE-1434041.
    Keywords: Geographic location/entity ; Estuaries ; Glaciers ; Circulation/ Dynamics ; Coastal flows ; Atm/Ocean Structure/ Phenomena ; Freshwater ; Snowmelt/icemelt ; Observational techniques and algorithms ; In situ oceanic observations
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  • 11
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2645-2662, doi:10.1175/JPO-D-15-0191.1.
    Description: The occurrence, drivers, and implications of small-scale O(2–5) km diameter coherent vortices, referred to as submesoscale eddies, over the inner shelf south of Martha’s Vineyard, Massachusetts, are examined using high-frequency (HF), radar-based, high-resolution (400 m) observations of surface currents. Within the 300 km2 study area, eddies occurred at rates of 1 and 4 day−1 in winter and summer, respectively. Most were less than 5 h in duration, smaller than 4 km in diameter, and rotated less than once over their lifespan; 60% of the eddies formed along the eastern edge of study area, adjacent to Wasque Shoal, and moved westward into the interior, often with relative vorticity greater than f. Eddy generation was linked to vortex stretching on the ebb and flood tide as well as the interaction of the spatially variable tide and the wind-driven currents; however, these features had complex patterns of surface divergence and stretching. Eddies located away from Wasque Shoal were related to the movement of wind-driven surface currents, as wind direction controlled where eddies formed as well as density effects. Using an analysis of particles advected within the radar-based surface currents, the observed eddies were found to be generally leaky, losing 60%–80% of particles over their lifespan, but still more retentive than the background flow. As a result, the combined translation and rotational effects of the observed eddies were an important source of lateral exchange for surface waters over the inner shelf.
    Description: The HF radar data utilized here were obtained using internal funding from the Woods Hole Oceanographic Institution. The analysis was supported by NSF OCE Grant 1332646.
    Description: 2017-02-19
    Keywords: Geographic location/entity ; Continental shelf/slope ; Circulation/ Dynamics ; Currents ; Eddies ; Observational techniques and algorithms ; Radars/Radar observations
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  • 12
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015):1189–1204, doi:10.1175/JPO-D-14-0122.1.
    Description: Winter outcropping of the Eighteen Degree Water (EDW) and its subsequent dispersion are studied using a ° eddy-resolving simulation of the Family of Linked Atlantic Modeling Experiments (FLAME). Outcropped EDW columns in the model simulations are detected in each winter from 1990 to 1999, and particles are deployed in the center of each outcropped EDW column. Subsequently, the trajectories of these particles are calculated for the following 5 yr. The particles slowly spread away from the outcropping region into the nonoutcropping/subducted EDW region south of ~30°N and eventually to the non-EDW region in the greater subtropical gyre. Approximately 30% of the particles are found in non-EDW waters 1 yr after deployment; after 5 yr, only 25% of the particles are found within EDW. The reoutcropping time is defined as the number of years between when a particle is originally deployed in an outcropping EDW column and when that particle is next found in an outcropping EDW column. Of the particles, 66% are found to reoutcrop as EDW in 1 yr, and less than 5% of the particles outcrop in each of the subsequent 4 yr. While the individual trajectories exhibit significant eddy-like motions, the time scale of reoutcropping is primarily set by the mean circulation. The dominance of reoutcropping in 1 yr suggests that EDW outcropping contributes considerably to the persistence of surface temperature anomalies from one winter to the next, that is, the reemergence of winter sea surface temperature anomalies.
    Description: We gratefully acknowledge the support from the NSF OCE Physical Oceanography program (NSF OCE-0961090 to Y-OK and J-JP; NSF OCE-0960776 to MSL and SFG; and NSF OCE-1242989 to Y-OK).
    Description: 2015-10-01
    Keywords: Circulation/ Dynamics ; Ocean circulation ; Atm/Ocean Structure/ Phenomena ; Water masses
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  • 13
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 1410–1425, doi:10.1175/JPO-D-14-0192.1.
    Description: The west-to-east crossover of boundary currents has been seen in mean circulation schemes from several past models of the Red Sea. This study investigates the mechanisms that produce and control the crossover in an idealized, eddy-resolving numerical model of the Red Sea. The authors also review the observational evidence and derive an analytical estimate for the crossover latitude. The surface buoyancy loss increases northward in the idealized model, and the resultant mean circulation consists of an anticyclonic gyre in the south and a cyclonic gyre in the north. In the midbasin, the northward surface flow crosses from the western boundary to the eastern boundary. Numerical experiments with different parameters indicate that the crossover latitude of the boundary currents changes with f0, β, and the meridional gradient of surface buoyancy forcing. In the analytical estimate, which is based on quasigeostrophic, β-plane dynamics, the crossover is predicted to lie at the latitude where the net potential vorticity advection (including an eddy component) is zero. Various terms in the potential vorticity budget can be estimated using a buoyancy budget, a thermal wind balance, and a parameterization of baroclinic instability.
    Description: This work is supported by Award USA 00002, KSA 00011, and KSA 00011/02 made by King Abdullah University of Science and Technology (KAUST), by National Science Foundation Grants OCE0927017, OCE1154641, and OCE85464100, and by the Woods Hole Oceanographic Institution Academic Program Office.
    Description: 2015-11-01
    Keywords: Circulation/ Dynamics ; Boundary currents ; Buoyancy ; Ocean circulation ; Ocean dynamics
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  • 14
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 1822–1842, doi:10.1175/JPO-D-14-0147.1.
    Description: Influences of time-dependent precipitation on water mass transformation and heat budgets in an idealized marginal sea are examined using theoretical and numerical models. The equations proposed by Spall in 2012 are extended to cases with time-dependent precipitation whose form is either a step function or a sinusoidal function. The theory predicts the differences in temperature and salinity between the convective water and the boundary current as well as the magnitudes of heat fluxes into the marginal sea and across the sea surface. Moreover, the theory reveals that there are three inherent time scales: relaxation time scales for temperature and salinity and a precipitation time scale. The relaxation time scales are determined by a steady solution of the theoretical model with steady precipitation. The relaxation time scale for temperature is always smaller than that for salinity as a result of not only the difference in the form of fluxes at the surface but also the variation in the eddy transport from the boundary current. These three time scales and the precipitation amplitude determine the strength of the ocean response to changes in precipitation and the phase relation between precipitation, changes in salinity and temperature, and changes in heat fluxes. It is demonstrated that the theoretical predictions agree qualitatively well with results from the eddy-resolving numerical model. This demonstrates the fundamental role of mesoscale eddies in the ocean response to time-dependent forcing and provides a framework with which to assess the extent to which observed variability in marginal sea convection and water mass transformation are consistent with an external forcing by variations in precipitation.
    Description: This work was initiated at the 2013 WHOI Geophysical Fluid Dynamics Summer Program, which was supported by the National Science Foundation and the Office of Naval Research. This work was also supported by Grant-in-Aid for Research Fellow (25·8466) of the Ministry of Education, Culture, Sports and Technology (MEXT), Japan, the Program for Leading Graduate Schools, MEXT, Japan (YY), and by the National Science Foundation Grant OCE-1232389 (MAS).
    Description: 2016-01-01
    Keywords: Circulation/ Dynamics ; Boundary currents ; Deep convection ; Eddies ; Ocean dynamics ; Atm/Ocean Structure/ Phenomena ; Precipitation
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  • 15
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2806–2819, doi:10.1175/JPO-D-15-0061.1.
    Description: An eastward-flowing current of a homogeneous fluid with velocity U, contained in a channel of width L, impinges on an island of width of O(L), and the resulting interaction and dynamics are studied for values of the supercriticality parameter, b = βL2/U, both larger and smaller than π2. The former case is subcritical with respect to Rossby waves, and the latter is supercritical. The nature of the flow field depends strongly on b, and in particular, the nature of the flow around the island and the proportion of the flow passing to the north or south of the island are sensitive to b and to the position of the island in the channel. The problem is studied analytically in a relatively simple, nonlinear quasigeostrophic and adiabatic framework and numerically with a shallow-water model that allows a qualitative extension of the results to the equator. Although the issues involved are motivated by the interaction of the Equatorial Undercurrent and the Galapagos Islands, the analysis presented here focuses on the fundamental issue of the distinctive nature of the flow as a function of Rossby wave criticality.
    Description: Supported by the National Science Foundation Grant OCE-0959381.
    Description: 2016-05-01
    Keywords: Circulation/ Dynamics ; Ocean circulation ; Ocean dynamics ; Waves, oceanic
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  • 16
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2773–2789, doi:10.1175/JPO-D-15-0031.1.
    Description: Tidal oscillatory salt transport, induced by the correlation between tidal variations in salinity and velocity, is an important term for the subtidal salt balance under the commonly used Eulerian method of salt transport decomposition. In this paper, its mechanisms in a partially stratified estuary are investigated with a numerical model of the Hudson estuary. During neap tides, when the estuary is strongly stratified, the tidal oscillatory salt transport is mainly due to the hydraulic response of the halocline to the longitudinal variation of topography. This mechanism does not involve vertical mixing, so it should not be regarded as oscillatory shear dispersion, but instead it should be regarded as advective transport of salt, which results from the vertical distortion of exchange flow obtained in the Eulerian decomposition by vertical fluctuations of the halocline. During spring tides, the estuary is weakly stratified, and vertical mixing plays a significant role in the tidal variation of salinity. In the spring tide regime, the tidal oscillatory salt transport is mainly due to oscillatory shear dispersion. In addition, the transient lateral circulation near large channel curvature causes the transverse tilt of the halocline. This mechanism has little effect on the cross-sectionally integrated tidal oscillatory salt transport, but it results in an apparent left–right cross-channel asymmetry of tidal oscillatory salt transport. With the isohaline framework, tidal oscillatory salt transport can be regarded as a part of the net estuarine salt transport, and the Lagrangian advective mechanism and dispersive mechanism can be distinguished.
    Description: Tao Wang was supported by the Open Research Fund of State Key Laboratory of Estuarine and Coastal Research (Grant SKLEC-KF201509) and Chinese Scholarship Council. Geyer was supported by by NSF Grant OCE 0926427. Wensheng Jiang was supported by NSFC-Shandong Joint Fund for Marine Science Research Centers (Grant U1406401).
    Description: 2016-05-01
    Keywords: Geographic location/entity ; Estuaries ; Circulation/ Dynamics ; Baroclinic flows ; Dispersion ; Shear structure/flows ; Atm/Ocean Structure/ Phenomena ; Diapycnal mixing ; Models and modeling ; Regional models
    Repository Name: Woods Hole Open Access Server
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  • 17
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 361–367, doi:10.1175/JPO-D-15-0171.1.
    Description: Idealized laboratory experiments investigate the glacier–ocean boundary dynamics near a vertical glacier in a two-layer stratified fluid. Discharge of meltwater runoff at the base of the glacier (subglacial discharge) enhances submarine melting. In the laboratory, the effect of multiple sources of subglacial discharge is simulated by introducing freshwater at freezing temperature from two point sources at the base of an ice block representing the glacier. The buoyant plumes of cold meltwater and subglacial discharge water entrain warm ambient water, rise vertically, and interact within a layer of depth H2 if the distance between the sources x0 is smaller than H2α/0.35, where α is the entrainment constant. The plume water detaches from the glacier face at the interface between the two layers and/or at the free surface, as confirmed by previous numerical studies and field observations. A plume model is used to explain the observed nonmonotonic dependence of submarine melting on the sources’ separation. The distance between the two sources influences the entrainment of warm water in the plumes and consequently the amount of submarine melting and the final location of the meltwater within the water column. Two interacting plumes located very close together are observed to melt approximately half as much as two independent plumes. The inclusion, or parameterization, of the dynamics regulating multiple plumes’ interaction is therefore necessary for a correct estimate of submarine melting. Hence, the distribution and number of sources of subglacial discharge may play an important role in glacial melt rates and fjord stratification and circulation.
    Description: Support to C.C. was given by the NSF Project OCE-1130008 and OCE-1434041. V.M.G. received support from the “Gori” Fellowship.
    Description: 2016-07-01
    Keywords: Geographic location/entity ; Glaciers ; Circulation/ Dynamics ; Buoyancy ; Entrainment ; Ocean dynamics ; Small scale processes ; Models and modeling ; Laboratory/physical models
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  • 18
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 327–348, doi:10.1175/JPO-D-15-0112.1.
    Description: Potential vorticity structure in two segments of the North Atlantic’s western boundary current is examined using concurrent, high-resolution measurements of hydrography and velocity from gliders. Spray gliders occupied 40 transects across the Loop Current in the Gulf of Mexico and 11 transects across the Gulf Stream downstream of Cape Hatteras. Cross-stream distributions of the Ertel potential vorticity and its components are calculated for each transect under the assumptions that all flow is in the direction of measured vertically averaged currents and that the flow is geostrophic. Mean cross-stream distributions of hydrographic properties, potential vorticity, and alongstream velocity are calculated for both the Loop Current and the detached Gulf Stream in both depth and density coordinates. Differences between these mean transects highlight the downstream changes in western boundary current structure. As the current increases its transport downstream, upper-layer potential vorticity is generally reduced because of the combined effects of increased anticyclonic relative vorticity, reduced stratification, and increased cross-stream density gradients. The only exception is within the 20-km-wide cyclonic flank of the Gulf Stream, where intense cyclonic relative vorticity results in more positive potential vorticity than in the Loop Current. Cross-stream gradients of mean potential vorticity satisfy necessary conditions for both barotropic and baroclinic instability within the western boundary current. Instances of very low or negative potential vorticity, which predispose the flow to various overturning instabilities, are observed in individual transects across both the Loop Current and the Gulf Stream.
    Description: Glider operations in the Gulf Stream were supported by the National Science Foundation under Grant OCE-0220769. Glider operations in the Gulf of Mexico were supported by BP. R.E.T. was supported by the Penzance Endowed Fund in Support of Assistant Scientists and the Independent Research and Development Program at WHOI.
    Description: 2016-07-01
    Keywords: Geographic location/entity ; North Atlantic Ocean ; Circulation/ Dynamics ; Boundary currents ; Potential vorticity ; Atm/Ocean Structure/ Phenomena ; Boundary currents
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  • 19
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2201-2218, doi:10.1175/JPO-D-16-0020.1.
    Description: This paper aims to test the validity, utility, and limitations of the lateral eddy diffusivity concept in a coastal environment through analyzing data from coupled drifter and dye releases within the footprint of a high-resolution (800 m) high-frequency radar south of Martha’s Vineyard, Massachusetts. Specifically, this study investigates how well a combination of radar-based velocities and drifter-derived diffusivities can reproduce observed dye spreading over an 8-h time interval. A drifter-based estimate of an anisotropic diffusivity tensor is used to parameterize small-scale motions that are unresolved and underresolved by the radar system. This leads to a significant improvement in the ability of the radar to reproduce the observed dye spreading.
    Description: IR, AK, and SL were supported by the NSF OCE Grant 1332646. IR was also supported by NASA Grant NNX14AH29G.
    Description: 2016-12-29
    Keywords: Circulation/ Dynamics ; Coastal flows ; Diffusion ; Lagrangian circulation/transport ; Observational techniques and algorithms ; Radars/Radar observations ; Models and modeling ; Tracers
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  • 20
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2267–2268, doi:10.1175/JPO-D-16-0057.1.
    Description: The original article that was the subject of this comment/reply can be found at http://journals.ametsoc.org/doi/abs/10.1175/JPO-D-15-0061.1.
    Description: 2017-01-12
    Keywords: Circulation/ Dynamics ; Circulation/ Dynamics
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  • 21
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2014. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 44 (2014): 3033–3053, doi:10.1175/JPO-D-13-0227.1.
    Description: The East Greenland Current (EGC) had long been considered the main pathway for the Denmark Strait overflow (DSO). Recent observations, however, indicate that the north Icelandic jet (NIJ), which flows westward along the north coast of Iceland, is a major separate pathway for the DSO. In this study a two-layer numerical model and complementary integral constraints are used to examine various pathways that lead to the DSO and to explore plausible mechanisms for the NIJ’s existence. In these simulations, a westward and NIJ-like current emerges as a robust feature and a main pathway for the Denmark Strait overflow. Its existence can be explained through circulation integrals around advantageous contours. One such constraint spells out the consequences of overflow water as a source of low potential vorticity. A stronger constraint can be added when the outflow occurs through two outlets: it takes the form of a circulation integral around the Iceland–Faroe Ridge. In either case, the direction of overall circulation about the contour can be deduced from the required frictional torques. Some effects of wind stress forcing are also examined. The overall positive curl of the wind forces cyclonic gyres in both layers, enhancing the East Greenland Current. The wind stress forcing weakens but does not eliminate the NIJ. It also modifies the sign of the deep circulation in various subbasins and alters the path by which overflow water is brought to the Faroe Bank Channel, all in ways that bring the idealized model more in line with observations. The sequence of numerical experiments separates the effects of wind and buoyancy forcing and shows how each is important.
    Description: This study has been supported by National Science Foundation (OCE0927017 and ARC1107412).
    Description: 2015-06-01
    Keywords: Circulation/ Dynamics ; Boundary currents ; Channel flows ; Meridional overturning circulation ; Ocean circulation ; Topographic effects
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  • 22
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 1356–1375, doi:10.1175/JPO-D-13-0259.1.
    Description: Eddy–mean flow interactions along the Kuroshio Extension (KE) jet are investigated using a vorticity budget of a high-resolution ocean model simulation, averaged over a 13-yr period. The simulation explicitly resolves mesoscale eddies in the KE and is forced with air–sea fluxes representing the years 1995–2007. A mean-eddy decomposition in a jet-following coordinate system removes the variability of the jet path from the eddy components of velocity; thus, eddy kinetic energy in the jet reference frame is substantially lower than in geographic coordinates and exhibits a cross-jet asymmetry that is consistent with the baroclinic instability criterion of the long-term mean field. The vorticity budget is computed in both geographic (i.e., Eulerian) and jet reference frames; the jet frame budget reveals several patterns of eddy forcing that are largely attributed to varicose modes of variability. Eddies tend to diffuse the relative vorticity minima/maxima that flank the jet, removing momentum from the fast-moving jet core and reinforcing the quasi-permanent meridional meanders in the mean jet. A pattern associated with the vertical stretching of relative vorticity in eddies indicates a deceleration (acceleration) of the jet coincident with northward (southward) quasi-permanent meanders. Eddy relative vorticity advection outside of the eastward jet core is balanced mostly by vertical stretching of the mean flow, which through baroclinic adjustment helps to drive the flanking recirculation gyres. The jet frame vorticity budget presents a well-defined picture of eddy activity, illustrating along-jet variations in eddy–mean flow interaction that may have implications for the jet’s dynamics and cross-frontal tracer fluxes.
    Description: A. S. Delman (ASD) and J. L. McClean (JLM) were supported by NSF Grant OCE-0850463 and Office of Science (BER), U.S. Department of Energy, Grant DE-FG02-05ER64119. ASD and J. Sprintall were also supported by a NASA Earth and Space Science Fellowship (NESSF), Grant NNX13AM93H. JLM was also supported by U.S. DOE Office of Science grant entitled “Ultra-High Resolution Global Climate Simulation” via a Los Alamos National Laboratory subcontract. S. R. Jayne was supported by NSF Grant OCE-0849808. Computational resources for the model run were provided by NSF Resource Grants TG-OCE110013 and TG-OCE130010.
    Description: 2015-11-01
    Keywords: Geographic location/entity ; North Pacific Ocean ; Circulation/ Dynamics ; Forcing ; Instability ; Mesoscale processes ; Atm/Ocean Structure/ Phenomena ; Jets ; Models and modeling ; General circulation models
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  • 23
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 1735–1756, doi:10.1175/JPO-D-14-0238.1.
    Description: The Lofoten basin of the Nordic Seas is recognized as a crucial component of the meridional overturning circulation in the North Atlantic because of the large horizontal extent of Atlantic Water and winter surface buoyancy loss. In this study, hydrographic and current measurements collected from a mooring deployed in the Lofoten basin from July 2010 to September 2012 are used to describe water mass transformation and the mesoscale eddy field. Winter mixed layer depths (MLDs) are observed to reach approximately 400 m, with larger MLDs and denser properties resulting from the colder 2010 winter. A heat budget of the upper water column requires lateral input, which balances the net annual heat loss of ~80 W m−2. The lateral flux is a result of mesoscale eddies, which dominate the velocity variability. Eddy velocities are enhanced in the upper 1000 m, with a barotropic component that reaches the bottom. Detailed examination of two eddies, from April and August 2012, highlights the variability of the eddy field and eddy properties. Temperature and salinity properties of the April eddy suggest that it originated from the slope current but was ventilated by surface fluxes. The properties within the eddy were similar to those of the mode water, indicating that convection within the eddies may make an important contribution to water mass transformation. A rough estimate of eddy flux per unit boundary current length suggests that fluxes in the Lofoten basin are larger than in the Labrador Sea because of the enhanced boundary current–interior density difference.
    Description: The work was supported by NSF OCE 0850416.
    Description: 2015-12-01
    Keywords: Circulation/ Dynamics ; Atmosphere-ocean interaction ; Boundary currents ; Eddies ; Fluxes ; Mesoscale processes ; Atm/Ocean Structure/ Phenomena ; Thermohaline circulation
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  • 24
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2381–2406, doi:10.1175/JPO-D-14-0086.1.
    Description: While near-inertial waves are known to be generated by atmospheric storms, recent observations in the Kuroshio Front find intense near-inertial internal-wave shear along sloping isopycnals, even during calm weather. Recent literature suggests that spontaneous generation of near-inertial waves by frontal instabilities could represent a major sink for the subinertial quasigeostrophic circulation. An unforced three-dimensional 1-km-resolution model, initialized with the observed cross-Kuroshio structure, is used to explore this mechanism. After several weeks, the model exhibits growth of 10–100-km-scale frontal meanders, accompanied by O(10) mW m−2 spontaneous generation of near-inertial waves associated with readjustment of submesoscale fronts forced out of balance by mesoscale confluent flows. These waves have properties resembling those in the observations. However, they are reabsorbed into the model Kuroshio Front with no more than 15% dissipating or radiating away. Thus, spontaneous generation of near-inertial waves represents a redistribution of quasigeostrophic energy rather than a significant sink.
    Description: “The Study of Kuroshio Ecosystem Dynamics for Sustainable Fisheries (SKED)” supported by MEXT, MIT-Hayashi Seed Fund, ONR (Awards N000140910196 and N000141210101), NSF (Award OCE 0928617, 0928138) for support.
    Description: 2016-03-01
    Keywords: Circulation/ Dynamics ; Frontogenesis/frontolysis ; Fronts ; Internal waves ; Turbulence ; Upwelling/downwelling ; Atm/Ocean Structure/ Phenomena ; Jets
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  • 25
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2497–2521, doi:10.1175/JPO-D-14-0128.1.
    Description: Oceanic density overturns are commonly used to parameterize the dissipation rate of turbulent kinetic energy. This method assumes a linear scaling between the Thorpe length scale LT and the Ozmidov length scale LO. Historic evidence supporting LT ~ LO has been shown for relatively weak shear-driven turbulence of the thermocline; however, little support for the method exists in regions of turbulence driven by the convective collapse of topographically influenced overturns that are large by open-ocean standards. This study presents a direct comparison of LT and LO, using vertical profiles of temperature and microstructure shear collected in the Luzon Strait—a site characterized by topographically influenced overturns up to O(100) m in scale. The comparison is also done for open-ocean sites in the Brazil basin and North Atlantic where overturns are generally smaller and due to different processes. A key result is that LT/LO increases with overturn size in a fashion similar to that observed in numerical studies of Kelvin–Helmholtz (K–H) instabilities for all sites but is most clear in data from the Luzon Strait. Resultant bias in parameterized dissipation is mitigated by ensemble averaging; however, a positive bias appears when instantaneous observations are depth and time integrated. For a series of profiles taken during a spring tidal period in the Luzon Strait, the integrated value is nearly an order of magnitude larger than that based on the microstructure observations. Physical arguments supporting LT ~ LO are revisited, and conceptual regimes explaining the relationship between LT/LO and a nondimensional overturn size are proposed. In a companion paper, Scotti obtains similar conclusions from energetics arguments and simulations.
    Description: B.D.M. and S.K.V. gratefully acknowledge the support of the Office of Naval Research under Grants N00014-12-1-0279, N00014-12-1-0282, and N00014-12-1-0938 (Program Manager: Dr. Terri Paluszkiewicz). S.K.V. also acknowledges support of the National Science Foundation under Grant OCE-1151838. L.S.L. acknowledges support for BBTRE by the National Science Foundation by Contract OCE94-15589 and NATRE and IWISE by the Office of Naval Research by Contracts N00014-92-1323 and N00014-10-10315. J.N.M. was supported through Grant 1256620 from the National Science Foundation and the Office of Naval Research (IWISE Project).
    Description: 2016-04-01
    Keywords: Circulation/ Dynamics ; Diapycnal mixing ; Small scale processes ; Turbulence ; Atm/Ocean Structure/ Phenomena ; Mixing ; Observational techniques and algorithms ; Profilers, oceanic ; Models and modeling ; Parameterization
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  • 26
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2621–2639, doi:10.1175/JPO-D-14-0239.1.
    Description: Measurements made as part of a large-scale experiment to examine wind-driven circulation and mixing in Chesapeake Bay demonstrate that circulations consistent with Langmuir circulation play an important role in surface boundary layer dynamics. Under conditions when the turbulent Langmuir number Lat is low (〈0.5), the surface mixed layer is characterized by 1) elevated vertical turbulent kinetic energy; 2) decreased anisotropy; 3) negative vertical velocity skewness indicative of strong/narrow downwelling and weak/broad upwelling; and 4) strong negative correlations between low-frequency vertical velocity and the velocity in the direction of wave propagation. These characteristics appear to be primarily the result of the vortex force associated with the surface wave field, but convection driven by a destabilizing heat flux is observed and appears to contribute significantly to the observed negative vertical velocity skewness. Conditions that favor convection usually also have strong Langmuir forcing, and these two processes probably both contribute to the surface mixed layer turbulence. Conditions in which traditional stress-driven turbulence is important are limited in this dataset. Unlike other shallow coastal systems where full water column Langmuir circulation has been observed, the salinity stratification in Chesapeake Bay is nearly always strong enough to prevent full-depth circulation from developing.
    Description: The funding for this research was provided by the National Science Foundation Grants OCE-1339032 and OCE-1338518.
    Description: 2016-04-01
    Keywords: Circulation/ Dynamics ; Convection ; Instability ; Mixing ; Turbulence ; Wave breaking ; Wind stress
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  • 27
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 29 (2016): 6201-6221, doi:10.1175/JCLI-D-15-0694.1.
    Description: Anomalous conditions in the tropical oceans, such as those related to El Niño–Southern Oscillation and the Indian Ocean dipole, have been previously blamed for extended droughts and wet periods in Australia. Yet the extent to which Australian wet and dry spells can be driven by internal atmospheric variability remains unclear. Natural variability experiments are examined to determine whether prolonged extreme wet and dry periods can arise from internal atmospheric and land variability alone. Results reveal that this is indeed the case; however, these dry and wet events are found to be less severe than in simulations incorporating coupled oceanic variability. Overall, ocean feedback processes increase the magnitude of Australian rainfall variability by about 30% and give rise to more spatially coherent rainfall impacts. Over mainland Australia, ocean interactions lead to more frequent extreme events, particularly during the rainy season. Over Tasmania, in contrast, ocean–atmosphere coupling increases mean rainfall throughout the year. While ocean variability makes Australian rainfall anomalies more severe, droughts and wet spells of duration longer than three years are equally likely to occur in both atmospheric- and ocean-driven simulations. Moreover, they are essentially indistinguishable from what one expects from a Gaussian white noise distribution. Internal atmosphere–land-driven megadroughts and megapluvials that last as long as ocean-driven events are also identified in the simulations. This suggests that oceanic variability may be less important than previously assumed for the long-term persistence of Australian rainfall anomalies. This poses a challenge to accurate prediction of long-term dry and wet spells for Australia.
    Description: This study was supported by the Australian Research Council (ARC) under ARC-DP1094784, ARC-DP-150101331, ARC-FL100100214, and funding for C.C.U. from the National Science Foundation under AGS-1602455 and the ARC Centre of Excellence for Climate System Science.
    Description: 2017-02-19
    Keywords: Circulation/ Dynamics ; Atmosphere-ocean interaction ; Atm/Ocean Structure/ Phenomena ; Drought ; Precipitation ; Physical Meteorology and Climatology ; Climate variability ; Forecasting ; Climate prediction ; Variability
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  • 28
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1309-1321, doi:10.1175/JPO-D-15-0068.1.
    Description: Direct measurements of oceanic turbulent parameters were taken upstream of and across Drake Passage, in the region of the Subantarctic and Polar Fronts. Values of turbulent kinetic energy dissipation rate ε estimated by microstructure are up to two orders of magnitude lower than previously published estimates in the upper 1000 m. Turbulence levels in Drake Passage are systematically higher than values upstream, regardless of season. The dissipation of thermal variance χ is enhanced at middepth throughout the surveys, with the highest values found in northern Drake Passage, where water mass variability is the most pronounced. Using the density ratio, evidence for double-diffusive instability is presented. Subject to double-diffusive physics, the estimates of diffusivity using the Osborn–Cox method are larger than ensemble statistics based on ε and the buoyancy frequency.
    Description: This work was supported by grants from the U.S. National Science Foundation.
    Description: 2016-10-05
    Keywords: Geographic location/entity ; Southern Ocean ; Circulation/ Dynamics ; Diapycnal mixing ; Mixing ; Turbulence ; Atm/Ocean Structure/ Phenomena ; Fronts ; Observational techniques and algorithms ; Profilers, oceanic
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  • 29
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1769-1783, doi:10.1175/JPO-D-15-0193.1.
    Description: High-resolution observations of velocity, salinity, and turbulence quantities were collected in a salt wedge estuary to quantify the efficiency of stratified mixing in a high-energy environment. During the ebb tide, a midwater column layer of strong shear and stratification developed, exhibiting near-critical gradient Richardson numbers and turbulent kinetic energy (TKE) dissipation rates greater than 10−4 m2 s−3, based on inertial subrange spectra. Collocated estimates of scalar variance dissipation from microconductivity sensors were used to estimate buoyancy flux and the flux Richardson number Rif. The majority of the samples were outside the boundary layer, based on the ratio of Ozmidov and boundary length scales, and had a mean Rif = 0.23 ± 0.01 (dissipation flux coefficient Γ = 0.30 ± 0.02) and a median gradient Richardson number Rig = 0.25. The boundary-influenced subset of the data had decreased efficiency, with Rif = 0.17 ± 0.02 (Γ = 0.20 ± 0.03) and median Rig = 0.16. The relationship between Rif and Rig was consistent with a turbulent Prandtl number of 1. Acoustic backscatter imagery revealed coherent braids in the mixing layer during the early ebb and a transition to more homogeneous turbulence in the midebb. A temporal trend in efficiency was also visible, with higher efficiency in the early ebb and lower efficiency in the late ebb when the bottom boundary layer had greater influence on the flow. These findings show that mixing efficiency of turbulence in a continuously forced, energetic, free shear layer can be significantly greater than the broadly cited upper bound from Osborn of 0.15–0.17.
    Description: Holleman was supported by the Devonshire Scholars program. The field study and the coauthors’ contributions were supported by NSF Grant OCE 0926427.
    Description: 2016-11-24
    Keywords: Circulation/ Dynamics ; Mixing ; Shear structure/flows ; Turbulence ; Observational techniques and algorithms ; Ship observations
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  • 30
    Publication Date: 2022-05-26
    Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Atmospheric and Oceanic Technology 33 (2016): 873-890, doi:10.1175/JTECH-D-15-0109.1.
    Description: Direct covariance flux (DCF) measurements taken from floating platforms are contaminated by wave-induced platform motions that need to be removed before computation of the turbulent fluxes. Several correction algorithms have been developed and successfully applied in earlier studies from research vessels and, most recently, by the use of moored buoys. The validation of those correction algorithms has so far been limited to short-duration comparisons against other floating platforms. Although these comparisons show in general a good agreement, there is still a lack of a rigorous validation of the method, required to understand the strengths and weaknesses of the existing motion-correction algorithms. This paper attempts to provide such a validation by a comparison of flux estimates from two DCF systems, one mounted on a moored buoy and one on the Air–Sea Interaction Tower (ASIT) at the Martha’s Vineyard Coastal Observatory, Massachusetts. The ASIT was specifically designed to minimize flow distortion over a wide range of wind directions from the open ocean for flux measurements. The flow measurements from the buoy system are corrected for wave-induced platform motions before computation of the turbulent heat and momentum fluxes. Flux estimates and cospectra of the corrected buoy data are found to be in very good agreement with those obtained from the ASIT. The comparison is also used to optimize the filter constants used in the motion-correction algorithm. The quantitative agreement between the buoy data and the ASIT demonstrates that the DCF method is applicable for turbulence measurements from small moving platforms, such as buoys.
    Description: This work was funded by the National Science Foundation Grant OCE04-24536 as part of the CLIVAR Mode Water Dynamic Experiment (CLIMODE).
    Keywords: Circulation/ Dynamics ; Turbulence ; Atm/Ocean Structure/ Phenomena ; Boundary layer ; Physical Meteorology and Climatology ; Air-sea interaction ; Observational techniques and algorithms ; Buoy observations ; Quality assurance/control
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  • 31
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 778–791, doi:10.1175/JPO-D-14-0164.1.
    Description: This study examines anisotropic transport properties of the eddying North Atlantic flow, using an idealized model of the double-gyre oceanic circulation and altimetry-derived velocities. The material transport by the time-dependent flow (quantified by the eddy diffusivity tensor) varies geographically and is anisotropic, that is, it has a well-defined direction of the maximum transport. One component of the time-dependent flow, zonally elongated large-scale transients, is particularly important for the anisotropy, as it corresponds to primarily zonal material transport and long correlation time scales. The importance of these large-scale zonal transients in the material distribution is further confirmed with simulations of idealized color dye tracers, which has implications for parameterizations of the eddy transport in non-eddy-resolving models.
    Description: IK would like to acknowledge support through the NSF Grant OCE-1154923. IR was supported by the NSF OCE-1154641 and NASA Grant NNX14AH29G.
    Description: 2015-09-01
    Keywords: Circulation/ Dynamics ; Eddies ; Lagrangian circulation/transport ; Mesoscale processes ; Ocean circulation ; Models and modeling ; Tracers
    Repository Name: Woods Hole Open Access Server
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  • 32
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 417-437, doi:10.1175/JPO-D-15-0055.1.
    Description: In the stratified ocean, turbulent mixing is primarily attributed to the breaking of internal waves. As such, internal waves provide a link between large-scale forcing and small-scale mixing. The internal wave field north of the Kerguelen Plateau is characterized using 914 high-resolution hydrographic profiles from novel Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats. Altogether, 46 coherent features are identified in the EM-APEX velocity profiles and interpreted in terms of internal wave kinematics. The large number of internal waves analyzed provides a quantitative framework for characterizing spatial variations in the internal wave field and for resolving generation versus propagation dynamics. Internal waves observed near the Kerguelen Plateau have a mean vertical wavelength of 200 m, a mean horizontal wavelength of 15 km, a mean period of 16 h, and a mean horizontal group velocity of 3 cm s−1. The internal wave characteristics are dependent on regional dynamics, suggesting that different generation mechanisms of internal waves dominate in different dynamical zones. The wave fields in the Subantarctic/Subtropical Front and the Polar Front Zone are influenced by the local small-scale topography and flow strength. The eddy-wave field is influenced by the large-scale flow structure, while the internal wave field in the Subantarctic Zone is controlled by atmospheric forcing. More importantly, the local generation of internal waves not only drives large-scale dissipation in the frontal region but also downstream from the plateau. Some internal waves in the frontal region are advected away from the plateau, contributing to mixing and stratification budgets elsewhere.
    Description: A.M. was supported by the joint CSIRO-University of Tasmania Quantitative Marine Science (QMS) program and the 2009 CSIRO Wealth from Ocean Flagship Collaborative Fund. K.L.P.’s salary support was provided by Woods Hole Oceanographic Institution bridge support funds. B.M.S. was supported by the Australian Climate Change Science Program.
    Description: 2016-06-07
    Keywords: Geographic location/entity ; Southern Ocean ; Circulation/ Dynamics ; Internal waves ; Mixing ; Wave properties ; Observational techniques and algorithms ; In situ oceanic observations ; Profilers, oceanic
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  • 33
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    American Meteorological Society
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1277-1284, doi:10.1175/JPO-D-16-0027.1.
    Description: The contemporary Arctic Ocean differs markedly from midlatitude, ice-free, and relatively warm oceans in the context of density-compensating temperature and salinity variations. These variations are invaluable tracers in the midlatitudes, revealing essential fundamental physical processes of the oceans, on scales from millimeters to thousands of kilometers. However, in the cold Arctic Ocean, temperature variations have little effect on density, and a measure of density-compensating variations in temperature and salinity (i.e., spiciness) is not appropriate. In general, temperature is simply a passive tracer, which implies that most of the heat transported in the Arctic Ocean relies entirely on the ocean dynamics determined by the salinity field. It is shown, however, that as the Arctic Ocean warms up, temperature will take on a new role in setting dynamical balances. Under continued warming, there exists the possibility for a regime shift in the mechanisms by which heat is transported in the Arctic Ocean. This may result in a cap on the storage of deep-ocean heat, having profound implications for future predictions of Arctic sea ice.
    Description: Support was provided by the National Science Foundation Division of Polar Programs Award 1350046 and Office of Naval Research Grant Number N00014-12-1-0110.
    Description: 2016-10-05
    Keywords: Geographic location/entity ; Arctic ; Circulation/ Dynamics ; Ocean dynamics
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  • 34
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1717-1734, doi:10.1175/JPO-D-15-0124.1.
    Description: The contribution of warm-core anticyclones shed by the Irminger Current off West Greenland, known as Irminger rings, to the restratification of the upper layers of the Labrador Sea is investigated in the 1/12° Family of Linked Atlantic Models Experiment (FLAME) model. The model output, covering the 1990–2004 period, shows strong similarities to observations of the Irminger Current as well as ring observations at a mooring located offshore of the eddy formation region in 2007–09. An analysis of fluxes in the model shows that while the majority of heat exchange with the interior indeed occurs at the site of the Irminger Current instability, the contribution of the coherent Irminger rings is modest (18%). Heat is provided to the convective region mainly through noncoherent anomalies and enhanced local mixing by the rings facilitating further exchange between the boundary and interior. The time variability of the eddy kinetic energy and the boundary to interior heat flux in the model are strongly correlated to the density gradient between the dense convective region and the more buoyant boundary current. In FLAME, the density variations of the boundary current are larger than those of the convective region, thereby largely controlling changes in lateral fluxes. Synchronous long-term trends in temperature in the boundary and the interior over the 15-yr simulation suggest that the heat flux relative to the temperature of the interior is largely steady on these time scales.
    Description: The authors were supported in this work by the U.S. National Science Foundation.
    Keywords: Geographic location/entity ; North Atlantic Ocean ; Circulation/ Dynamics ; Anticyclones ; Boundary currents ; Convection ; Eddies ; Fluxes
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  • 35
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1823-1837, doi:10.1175/JPO-D-15-0165.1.
    Description: Measurements just beneath the ocean surface demonstrate that the primary mechanism by which energy from breaking waves is transmitted into the water column is through the work done by the covariance of turbulent pressure and velocity fluctuations. The convergence in the vertical transport of turbulent kinetic energy (TKE) balances the dissipation rate of TKE at first order and is nearly an order of magnitude greater than the sum of the integrated Eulerian and Stokes shear production. The measured TKE transport is consistent with a simple conceptual model that assumes roughly half of the surface flux of TKE by wave breaking is transmitted to depths greater than the significant wave height. During conditions when breaking waves are inferred, the direction of momentum flux is more aligned with the direction of wave propagation than with the wind direction. Both the energy and momentum fluxes occur at frequencies much lower than the wave band, consistent with the time scales associated with wave breaking. The largest instantaneous values of momentum flux are associated with strong downward vertical velocity perturbations, in contrast to the pressure work, which is associated with strong drops in pressure and upward vertical velocity perturbations.
    Description: Funding for this research was provided by the National Science Foundation Grants OCE-1339032 and OCE-1338518
    Keywords: Circulation/ Dynamics ; Energy transport ; Mixing ; Momentum ; Turbulence ; Wave breaking ; Waves, oceanic
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  • 36
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 2143-2156, doi:10.1175/JPO-D-15-0213.1.
    Description: Measurements of pressure near the surface in conditions of wind sea and swell are reported. Swell, or waves that overrun the wind, produces an upward flux of energy and momentum from waves to the wind and corresponding attenuation of the swell waves. The estimates of growth of wind sea are consistent with existing parameterizations. The attenuation of swell in the field is considerably smaller than existing measurements in the laboratory.
    Keywords: Circulation/ Dynamics ; Pressure ; Wind stress ; Wind waves ; Physical Meteorology and Climatology ; Air-sea interaction
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  • 37
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 29 (2016): 1545-1571, doi:10.1175/JCLI-D-15-0509.1.
    Description: Three sediment records of sea surface temperature (SST) are analyzed that originate from distant locations in the North Atlantic, have centennial-to-multicentennial resolution, are based on the same reconstruction method and chronological assumptions, and span the past 15 000 yr. Using recursive least squares techniques, an estimate of the time-dependent North Atlantic SST field over the last 15 kyr is sought that is consistent with both the SST records and a surface ocean circulation model, given estimates of their respective error (co)variances. Under the authors’ assumptions about data and model errors, it is found that the 10°C mixed layer isotherm, which approximately traces the modern Subpolar Front, would have moved by ~15° of latitude southward (northward) in the eastern North Atlantic at the onset (termination) of the Younger Dryas cold interval (YD), a result significant at the level of two standard deviations in the isotherm position. In contrast, meridional movements of the isotherm in the Newfoundland basin are estimated to be small and not significant. Thus, the isotherm would have pivoted twice around a region southeast of the Grand Banks, with a southwest–northeast orientation during the warm intervals of the Bølling–Allerød and the Holocene and a more zonal orientation and southerly position during the cold interval of the YD. This study provides an assessment of the significance of similar previous inferences and illustrates the potential of recursive least squares in paleoceanography.
    Description: OM acknowledges support from the U.S. National Science Foundation. CW acknowledges support from the European Research Council ERC Grant ACCLIMATE 339108.
    Description: 2016-08-19
    Keywords: Geographic location/entity ; North Atlantic Ocean ; Circulation/ Dynamics ; Fronts ; Mathematical and statistical techniques ; Inverse methods ; Kalman filters ; Variability ; Climate variability ; Oceanic variability
    Repository Name: Woods Hole Open Access Server
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  • 38
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 294–312, doi:10.1175/JPO-D-14-0104.1.
    Description: Model analyses of an alongshelf flow over a continental shelf and slope reveal upwelling near the shelf break. A stratified, initially uniform, alongshelf flow undergoes a rapid adjustment with notable differences onshore and offshore of the shelf break. Over the shelf, a bottom boundary layer and an offshore bottom Ekman transport develop within an inertial period. Over the slope, the bottom offshore transport is reduced from the shelf’s bottom transport by two processes. First, advection of buoyancy downslope induces vertical mixing, destratifying, and thickening the bottom boundary layer. The downward-tilting isopycnals reduce the geostrophic speed near the bottom. The reduced bottom stress weakens the offshore Ekman transport, a process known as buoyancy shutdown of the Ekman transport. Second, the thickening bottom boundary layer and weakening near-bottom speeds are balanced by an upslope ageostrophic transport. The convergence in the bottom transport induces adiabatic upwelling offshore of the shelf break. For a time period after the initial adjustment, scalings are identified for the upwelling speed and the length scale over which it occurs. Numerical experiments are used to test the scalings for a range of initial speeds and stratifications. Upwelling occurs within an inertial period, reaching values of up to 10 m day−1 within 2 to 7 km offshore of the shelf break. Upwelling drives an interior secondary circulation that accelerates the alongshelf flow over the slope, forming a shelfbreak jet. The model results are compared with upwelling estimates from other models and observations near the Middle Atlantic Bight shelf break.
    Description: J. Benthuysen acknowledges support from the ARC Centre of Excellence for Climate System Science (CE110001028) and the MIT/WHOI Joint Program, where this work was initiated.
    Description: 2015-07-01
    Keywords: Circulation/ Dynamics ; Boundary currents ; Diapycnal mixing ; Ekman pumping/transport ; Mixing ; Topographic effects ; Upwelling/downwelling
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  • 39
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 104–132, doi:10.1175/JPO-D-14-0032.1.
    Description: Three mechanisms for self-induced Ekman pumping in the interiors of mesoscale ocean eddies are investigated. The first arises from the surface stress that occurs because of differences between surface wind and ocean velocities, resulting in Ekman upwelling and downwelling in the cores of anticyclones and cyclones, respectively. The second mechanism arises from the interaction of the surface stress with the surface current vorticity gradient, resulting in dipoles of Ekman upwelling and downwelling. The third mechanism arises from eddy-induced spatial variability of sea surface temperature (SST), which generates a curl of the stress and therefore Ekman pumping in regions of crosswind SST gradients. The spatial structures and relative magnitudes of the three contributions to eddy-induced Ekman pumping are investigated by collocating satellite-based measurements of SST, geostrophic velocity, and surface winds to the interiors of eddies identified from their sea surface height signatures. On average, eddy-induced Ekman pumping velocities approach O(10) cm day−1. SST-induced Ekman pumping is usually secondary to the two current-induced mechanisms for Ekman pumping. Notable exceptions are the midlatitude extensions of western boundary currents and the Antarctic Circumpolar Current, where SST gradients are strong and all three mechanisms for eddy-induced Ekman pumping are comparable in magnitude. Because the polarity of current-induced curl of the surface stress opposes that of the eddy, the associated Ekman pumping attenuates the eddies. The decay time scale of this attenuation is proportional to the vertical scale of the eddy and inversely proportional to the wind speed. For typical values of these parameters, the decay time scale is about 1.3 yr.
    Description: This work was funded by NASA Grants NNX08AI80G, NNX08AR37G, NNX13AD78G, NNX10AE91G, NNX13AE47G, and NNX10AO98G.
    Description: 2015-07-01
    Keywords: Circulation/ Dynamics ; Atmosphere-ocean interaction ; Eddies ; Ekman pumping/transport ; Atm/Ocean Structure/ Phenomena ; Eddies ; Ekman pumping ; Observational techniques and algorithms ; Satellite observations
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  • 40
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 29 (2016): 3143-3159, doi:10.1175/JCLI-D-15-0520.1.
    Description: Moisture originating from the subtropical North Atlantic feeds precipitation throughout the Western Hemisphere. This ocean-to-land moisture transport leaves its imprint on sea surface salinity (SSS), enabling SSS over the subtropical oceans to be used as an indicator of terrestrial precipitation. This study demonstrates that springtime SSS over the northwestern portion of the subtropical North Atlantic significantly correlates with summertime precipitation over the U.S. Midwest. The linkage between springtime SSS and the Midwest summer precipitation is established through ocean-to-land moisture transport followed by a soil moisture feedback over the southern United States. In the spring, high SSS over the northwestern subtropical Atlantic coincides with a local increase in moisture flux divergence. The moisture flux is then directed toward and converges over the southern United States, which experiences increased precipitation and soil moisture. The increased soil moisture influences the regional water cycle both thermodynamically and dynamically, leading to excessive summer precipitation in the Midwest. Thermodynamically, the increased soil moisture tends to moisten the lower troposphere and enhances the meridional humidity gradient north of 36°N. Thus, more moisture will be transported and converged into the Midwest by the climatological low-level wind. Dynamically, the increases in soil moisture over the southern United States enhance the west–east soil moisture gradient eastward of the Rocky Mountains, which can help to intensify the Great Plains low-level jet in the summer, converging more moisture into the Midwest. Owing to these robust physical linkages, the springtime SSS outweighs the leading SST modes in predicting the Midwest summer precipitation and significantly improves rainfall prediction in this region.
    Description: L. L. is supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution (WHOI), with funding provided by the Ocean and Climate Change Institute (OCCI). R. W. S. is supported by NASA Grant NNX12AF59G S03 and NSF Grant OCE-1129646. C. C. U. is supported by NSF Grant AGS-1355339. K. B. K. is supported by the Alfred P. Sloan Foundation and the James E. and Barbara V. Moltz Fellowship administered by the WHOI OCCI.
    Description: 2016-10-19
    Keywords: Circulation/ Dynamics ; Hydrologic cycle ; Physical Meteorology and Climatology ; Moisture/moisture budget ; Salinity
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  • 41
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    American Meteorological Society
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 33 (2016): 1225-1235, doi:10.1175/JTECH-D-15-0115.1.
    Description: Accurate estimation of the transport probabilities among regions in the ocean provides valuable information for understanding plankton transport, the spread of pollutants, and the movement of water masses. Individual-based particle-tracking models simulate a large ensemble of Lagrangian particles and are a common method to estimate these transport probabilities. Simulating a large ensemble of Lagrangian particles is computationally expensive, and appropriately allocating resources can reduce the cost of this method. Two universal questions in the design of studies that use Lagrangian particle tracking are how many particles to release and how to distribute particle releases. A method is presented for tailoring the number and the release location of particles to most effectively achieve the objectives of a study. The method detailed here is a sequential analysis procedure that seeks to minimize the number of particles that are required to satisfy a predefined metric of result quality. The study assesses the result quality as the precision of the estimates for the elements of a transport matrix and also describes how the method may be extended for use with other metrics. Applying this methodology to both a theoretical system and a particle transport model of the Gulf of Maine results in more precise estimates of the transport probabilities with fewer particles than from uniformly or randomly distributing particle releases. The application of this method can help reduce the cost of and increase the robustness of results from studies that use Lagrangian particles.
    Description: This research was supported by the Department of Defense (DoD) through the National Defense Science and Engineering Graduate Fellowship (NDSEG) program and the National Science Foundation through Grant OCE-1459133 and Grant OCE-1031256.
    Description: 2016-12-02
    Keywords: Circulation/ Dynamics ; Lagrangian circulation/transport ; Models and modeling ; Model evaluation/performance ; Ocean models ; Tracers
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  • 42
    Publication Date: 2015-09-19
    Description: Recent releases of genome three-dimensional (3D) structures have the potential to transform our understanding of genomes. Nonetheless, the storage technology and visualization tools need to evolve to offer to the scientific community fast and convenient access to these data. We introduce simultaneously a database system to store and query 3D genomic data ( 3DBG ), and a 3D genome browser to visualize and explore 3D genome structures ( 3DGB ). We benchmark 3DBG against state-of-the-art systems and demonstrate that it is faster than previous solutions, and importantly gracefully scales with the size of data. We also illustrate the usefulness of our 3D genome Web browser to explore human genome structures. The 3D genome browser is available at http://3dgb.cs.mcgill.ca/ .
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
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  • 43
    Publication Date: 2015-05-29
    Description: Identification of transcription units (TUs) encoded in a bacterial genome is essential to elucidation of transcriptional regulation of the organism. To gain a detailed understanding of the dynamically composed TU structures, we have used four strand-specific RNA-seq (ssRNA-seq) datasets collected under two experimental conditions to derive the genomic TU organization of Clostridium thermocellum using a machine-learning approach. Our method accurately predicted the genomic boundaries of individual TUs based on two sets of parameters measuring the RNA-seq expression patterns across the genome: expression-level continuity and variance. A total of 2590 distinct TUs are predicted based on the four RNA-seq datasets. Among the predicted TUs, 44% have multiple genes. We assessed our prediction method on an independent set of RNA-seq data with longer reads. The evaluation confirmed the high quality of the predicted TUs. Functional enrichment analyses on a selected subset of the predicted TUs revealed interesting biology. To demonstrate the generality of the prediction method, we have also applied the method to RNA-seq data collected on Escherichia coli and achieved high prediction accuracies. The TU prediction program named SeqTU is publicly available at https://code.google.com/p/seqtu/ . We expect that the predicted TUs can serve as the baseline information for studying transcriptional and post-transcriptional regulation in C. thermocellum and other bacteria.
    Keywords: Computational Methods, Genomics
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  • 44
    Publication Date: 2015-05-29
    Description: Detecting genetic variation is one of the main applications of high-throughput sequencing, but is still challenging wherever aligning short reads poses ambiguities. Current state-of-the-art variant calling approaches avoid such regions, arguing that it is necessary to sacrifice detection sensitivity to limit false discovery. We developed a method that links candidate variant positions within repetitive genomic regions into clusters. The technique relies on a resource, a thesaurus of genetic variation, that enumerates genomic regions with similar sequence. The resource is computationally intensive to generate, but once compiled can be applied efficiently to annotate and prioritize variants in repetitive regions. We show that thesaurus annotation can reduce the rate of false variant calls due to mappability by up to three orders of magnitude. We apply the technique to whole genome datasets and establish that called variants in low mappability regions annotated using the thesaurus can be experimentally validated. We then extend the analysis to a large panel of exomes to show that the annotation technique opens possibilities to study variation in hereto hidden and under-studied parts of the genome.
    Keywords: Computational Methods, Genomics
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  • 45
    Publication Date: 2016-06-21
    Description: Assigning cancer patients to the most effective treatments requires an understanding of the molecular basis of their disease. While DNA-based molecular profiling approaches have flourished over the past several years to transform our understanding of driver pathways across a broad range of tumors, a systematic characterization of key driver pathways based on RNA data has not been undertaken. Here we introduce a new approach for predicting the status of driver cancer pathways based on signature functions derived from RNA sequencing data. To identify the driver cancer pathways of interest, we mined DNA variant data from TCGA and nominated driver alterations in seven major cancer pathways in breast, ovarian and colon cancer tumors. The activation status of these driver pathways were then characterized using RNA sequencing data by constructing classification signature functions in training datasets and then testing the accuracy of the signatures in test datasets. The signature functions differentiate well tumors with nominated pathway activation from tumors with no signs of activation: average AUC equals to 0.83. Our results confirm that driver genomic alterations are distinctively displayed at the transcriptional level and that the transcriptional signatures can generally provide an alternative to DNA sequencing methods in detecting specific driver pathways.
    Keywords: Computational Methods, Genomics
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  • 46
    Publication Date: 2016-06-21
    Description: Modeling the properties and functions of DNA sequences is an important, but challenging task in the broad field of genomics. This task is particularly difficult for non-coding DNA, the vast majority of which is still poorly understood in terms of function. A powerful predictive model for the function of non-coding DNA can have enormous benefit for both basic science and translational research because over 98% of the human genome is non-coding and 93% of disease-associated variants lie in these regions. To address this need, we propose DanQ, a novel hybrid convolutional and bi-directional long short-term memory recurrent neural network framework for predicting non-coding function de novo from sequence. In the DanQ model, the convolution layer captures regulatory motifs, while the recurrent layer captures long-term dependencies between the motifs in order to learn a regulatory ‘grammar’ to improve predictions. DanQ improves considerably upon other models across several metrics. For some regulatory markers, DanQ can achieve over a 50% relative improvement in the area under the precision-recall curve metric compared to related models. We have made the source code available at the github repository http://github.com/uci-cbcl/DanQ .
    Keywords: Computational Methods, Genomics
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  • 47
    Publication Date: 2016-06-21
    Description: Molecular sequences in public databases are mostly annotated by the submitting authors without further validation. This procedure can generate erroneous taxonomic sequence labels. Mislabeled sequences are hard to identify, and they can induce downstream errors because new sequences are typically annotated using existing ones. Furthermore, taxonomic mislabelings in reference sequence databases can bias metagenetic studies which rely on the taxonomy. Despite significant efforts to improve the quality of taxonomic annotations, the curation rate is low because of the labor-intensive manual curation process. Here, we present SATIVA, a phylogeny-aware method to automatically identify taxonomically mislabeled sequences (‘mislabels’) using statistical models of evolution. We use the Evolutionary Placement Algorithm (EPA) to detect and score sequences whose taxonomic annotation is not supported by the underlying phylogenetic signal, and automatically propose a corrected taxonomic classification for those. Using simulated data, we show that our method attains high accuracy for identification (96.9% sensitivity/91.7% precision) as well as correction (94.9% sensitivity/89.9% precision) of mislabels. Furthermore, an analysis of four widely used microbial 16S reference databases (Greengenes, LTP, RDP and SILVA) indicates that they currently contain between 0.2% and 2.5% mislabels. Finally, we use SATIVA to perform an in-depth evaluation of alternative taxonomies for Cyanobacteria. SATIVA is freely available at https://github.com/amkozlov/sativa .
    Keywords: Computational Methods, Genomics
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  • 48
    Publication Date: 2016-06-21
    Description: DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with ( n = 9) or without ( n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (~90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3'UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5–10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.
    Keywords: Computational Methods, Genomics
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  • 49
    Publication Date: 2016-05-06
    Description: The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries.
    Keywords: Computational Methods, Genomics
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  • 50
    Publication Date: 2016-05-06
    Description: Single cell RNA-seq experiments provide valuable insight into cellular heterogeneity but suffer from low coverage, 3' bias and technical noise. These unique properties of single cell RNA-seq data make study of alternative splicing difficult, and thus most single cell studies have restricted analysis of transcriptome variation to the gene level. To address these limitations, we developed SingleSplice, which uses a statistical model to detect genes whose isoform usage shows biological variation significantly exceeding technical noise in a population of single cells. Importantly, SingleSplice is tailored to the unique demands of single cell analysis, detecting isoform usage differences without attempting to infer expression levels for full-length transcripts. Using data from spike-in transcripts, we found that our approach detects variation in isoform usage among single cells with high sensitivity and specificity. We also applied SingleSplice to data from mouse embryonic stem cells and discovered a set of genes that show significant biological variation in isoform usage across the set of cells. A subset of these isoform differences are linked to cell cycle stage, suggesting a novel connection between alternative splicing and the cell cycle.
    Keywords: Computational Methods, Genomics
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  • 51
    Publication Date: 2016-07-09
    Description: The recent super-exponential growth in the amount of sequencing data generated worldwide has put techniques for compressed storage into the focus. Most available solutions, however, are strictly tied to specific bioinformatics formats, sometimes inheriting from them suboptimal design choices; this hinders flexible and effective data sharing. Here, we present CARGO (Compressed ARchiving for GenOmics), a high-level framework to automatically generate software systems optimized for the compressed storage of arbitrary types of large genomic data collections. Straightforward applications of our approach to FASTQ and SAM archives require a few lines of code, produce solutions that match and sometimes outperform specialized format-tailored compressors and scale well to multi-TB datasets. All CARGO software components can be freely downloaded for academic and non-commercial use from http://bio-cargo.sourceforge.net .
    Keywords: Computational Methods, Genomics
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  • 52
    Publication Date: 2016-07-09
    Description: Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al . demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/.
    Keywords: Computational Methods, Genomics
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  • 53
    Publication Date: 2016-07-09
    Description: Many genomes display high levels of heterozygosity (i.e. presence of different alleles at the same loci in homologous chromosomes), being those of hybrid organisms an extreme such case. The assembly of highly heterozygous genomes from short sequencing reads is a challenging task because it is difficult to accurately recover the different haplotypes. When confronted with highly heterozygous genomes, the standard assembly process tends to collapse homozygous regions and reports heterozygous regions in alternative contigs. The boundaries between homozygous and heterozygous regions result in multiple assembly paths that are hard to resolve, which leads to highly fragmented assemblies with a total size larger than expected. This, in turn, causes numerous problems in downstream analyses such as fragmented gene models, wrong gene copy number, or broken synteny. To circumvent these caveats we have developed a pipeline that specifically deals with the assembly of heterozygous genomes by introducing a step to recognise and selectively remove alternative heterozygous contigs. We tested our pipeline on simulated and naturally-occurring heterozygous genomes and compared its accuracy to other existing tools. Our method is freely available at https://github.com/Gabaldonlab/redundans .
    Keywords: Computational Methods, Genomics
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  • 54
    Publication Date: 2015-05-03
    Description: Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease.
    Keywords: Computational Methods, Genomics
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  • 55
    Publication Date: 2015-05-03
    Description: The Metabolic Models Reconstruction Using Genome-Scale Information ( merlin ) tool is a user-friendly Java application that aids the reconstruction of genome-scale metabolic models for any organism that has its genome sequenced. It performs the major steps of the reconstruction process, including the functional genomic annotation of the whole genome and subsequent construction of the portfolio of reactions. Moreover, merlin includes tools for the identification and annotation of genes encoding transport proteins, generating the transport reactions for those carriers. It also performs the compartmentalisation of the model, predicting the organelle localisation of the proteins encoded in the genome and thus the localisation of the metabolites involved in the reactions promoted by such enzymes. The gene-proteins-reactions (GPR) associations are automatically generated and included in the model. Finally, merlin expedites the transition from genomic data to draft metabolic models reconstructions exported in the SBML standard format, allowing the user to have a preliminary view of the biochemical network, which can be manually curated within the environment provided by merlin .
    Keywords: Computational Methods, Genomics
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  • 56
    Publication Date: 2015-05-03
    Description: For eukaryotic cells, the biological processes involving regulatory DNA elements play an important role in cell cycle. Understanding 3D spatial arrangements of chromosomes and revealing long-range chromatin interactions are critical to decipher these biological processes. In recent years, chromosome conformation capture (3C) related techniques have been developed to measure the interaction frequencies between long-range genome loci, which have provided a great opportunity to decode the 3D organization of the genome. In this paper, we develop a new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data. By modeling each chromosome as a polymer chain, we define the conformational energy based on our current knowledge on polymer physics and use it as prior information in the Bayesian framework. We also propose an expectation-maximization (EM) based algorithm to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data. We have validated our Bayesian inference approach through cross-validation and verified the computed chromatin conformations using the geometric constraints derived from fluorescence in situ hybridization (FISH) experiments. We have further confirmed the inferred chromatin structures using the known genetic interactions derived from other studies in the literature. Our test results have indicated that our Bayesian framework can compute an accurate ensemble of 3D chromatin conformations that best interpret the distance constraints derived from 3C-based data and also agree with other sources of geometric constraints derived from experimental evidence in the previous studies. The source code of our approach can be found in https://github.com/wangsy11/InfMod3DGen .
    Keywords: Computational Methods, Genomics
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  • 57
    Publication Date: 2015-05-03
    Description: Characterization of cell type specific regulatory networks and elements is a major challenge in genomics, and emerging strategies frequently employ high-throughput genome-wide assays of transcription factor (TF) to DNA binding, histone modifications or chromatin state. However, these experiments remain too difficult/expensive for many laboratories to apply comprehensively to their system of interest. Here, we explore the potential of elucidating regulatory systems in varied cell types using computational techniques that rely on only data of gene expression, low-resolution chromatin accessibility, and TF–DNA binding specificities (‘motifs’). We show that static computational motif scans overlaid with chromatin accessibility data reasonably approximate experimentally measured TF–DNA binding. We demonstrate that predicted binding profiles and expression patterns of hundreds of TFs are sufficient to identify major regulators of ~200 spatiotemporal expression domains in the Drosophila embryo. We are then able to learn reliable statistical models of enhancer activity for over 70 expression domains and apply those models to annotate domain specific enhancers genome-wide. Throughout this work, we apply our motif and accessibility based approach to comprehensively characterize the regulatory network of fruitfly embryonic development and show that the accuracy of our computational method compares favorably to approaches that rely on data from many experimental assays.
    Keywords: Computational Methods, Genomics
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  • 58
    Publication Date: 2015-06-24
    Description: Much of the inter-individual variation in gene expression is triggered via perturbations of signaling networks by DNA variants. We present a novel probabilistic approach for identifying the particular pathways by which DNA variants perturb the signaling network. Our procedure, called PINE, relies on a systematic integration of established biological knowledge of signaling networks with data on transcriptional responses to various experimental conditions. Unlike previous approaches, PINE provides statistical aspects that are critical for prioritizing hypotheses for followup experiments. Using simulated data, we show that higher accuracy is attained with PINE than with existing methods. We used PINE to analyze transcriptional responses of immune dendritic cells to several pathogenic stimulations. PINE identified statistically significant genetic perturbations in the pathogen-sensing signaling network, suggesting previously uncharacterized regulatory mechanisms for functional DNA variants.
    Keywords: Computational Methods, Genomics
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  • 59
    Publication Date: 2015-08-29
    Description: Variations in sample quality are frequently encountered in small RNA-sequencing experiments, and pose a major challenge in a differential expression analysis. Removal of high variation samples reduces noise, but at a cost of reducing power, thus limiting our ability to detect biologically meaningful changes. Similarly, retaining these samples in the analysis may not reveal any statistically significant changes due to the higher noise level. A compromise is to use all available data, but to down-weight the observations from more variable samples. We describe a statistical approach that facilitates this by modelling heterogeneity at both the sample and observational levels as part of the differential expression analysis. At the sample level this is achieved by fitting a log-linear variance model that includes common sample-specific or group-specific parameters that are shared between genes. The estimated sample variance factors are then converted to weights and combined with observational level weights obtained from the mean–variance relationship of the log-counts-per-million using ‘voom’. A comprehensive analysis involving both simulations and experimental RNA-sequencing data demonstrates that this strategy leads to a universally more powerful analysis and fewer false discoveries when compared to conventional approaches. This methodology has wide application and is implemented in the open-source ‘limma’ package.
    Keywords: Computational Methods, Genomics
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  • 60
    Publication Date: 2015-08-29
    Description: Most mammalian genes have mRNA variants due to alternative promoter usage, alternative splicing, and alternative cleavage and polyadenylation. Expression of alternative RNA isoforms has been found to be associated with tumorigenesis, proliferation and differentiation. Detection of condition-associated transcription variation requires association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on count data with replicates. Although the Cochran Mantel Haenszel (CMH) approach can handle replicated count data, our simulations showed that multiple CMH tests still had very low power. To identify condition-associated variation of transcription, we here proposed a ranking analysis of chi-squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric method and has accurate and conservative estimation of FDR profile. Simulations demonstrated that RAX2 performs well in finding condition-associated transcription variants. We applied RAX2 to primary T-cell transcriptomic data and identified 1610 (16.3%) tags associated in transcription with immune stimulation at FDR 〈 0.05. Most of these tags also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation short RNA isoforms were preferably used.
    Keywords: Computational Methods, Genomics
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  • 61
    Publication Date: 2015-12-16
    Description: To understand how transposon landscapes (TLs) vary across animal genomes, we describe a new method called the Transposon Insertion and Depletion AnaLyzer (TIDAL) and a database of 〉300 TLs in Drosophila melanogaster (TIDAL-Fly). Our analysis reveals pervasive TL diversity across cell lines and fly strains, even for identically named sub-strains from different laboratories such as the ISO1 strain used for the reference genome sequence. On average, 〉500 novel insertions exist in every lab strain, inbred strains of the Drosophila Genetic Reference Panel (DGRP), and fly isolates in the Drosophila Genome Nexus (DGN). A minority (〈25%) of transposon families comprise the majority (〉70%) of TL diversity across fly strains. A sharp contrast between insertion and depletion patterns indicates that many transposons are unique to the ISO1 reference genome sequence. Although TL diversity from fly strains reaches asymptotic limits with increasing sequencing depth, rampant TL diversity causes unsaturated detection of TLs in pools of flies. Finally, we show novel transposon insertions negatively correlate with Piwi-interacting RNA (piRNA) levels for most transposon families, except for the highly-abundant roo retrotransposon. Our study provides a useful resource for Drosophila geneticists to understand how transposons create extensive genomic diversity in fly cell lines and strains.
    Keywords: Computational Methods, Genomics
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  • 62
    Publication Date: 2016-06-03
    Description: Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments.
    Keywords: Computational Methods, Genomics
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  • 63
    Publication Date: 2016-06-03
    Description: The ability to integrate ‘omics’ (i.e. transcriptomics and proteomics) is becoming increasingly important to the understanding of regulatory mechanisms. There are currently no tools available to identify differentially expressed genes (DEGs) across different ‘omics’ data types or multi-dimensional data including time courses. We present fCI (f-divergence Cut-out Index), a model capable of simultaneously identifying DEGs from continuous and discrete transcriptomic, proteomic and integrated proteogenomic data. We show that fCI can be used across multiple diverse sets of data and can unambiguously find genes that show functional modulation, developmental changes or misregulation. Applying fCI to several proteogenomics datasets, we identified a number of important genes that showed distinctive regulation patterns. The package fCI is available at R Bioconductor and http://software.steenlab.org/fCI/ .
    Keywords: Computational Methods, Genomics
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  • 64
    Publication Date: 2016-06-03
    Description: Next generation sequencing of cellular RNA is making it possible to characterize genes and alternative splicing in unprecedented detail. However, designing bioinformatics tools to accurately capture splicing variation has proven difficult. Current programs can find major isoforms of a gene but miss lower abundance variants, or are sensitive but imprecise. CLASS2 is a novel open source tool for accurate genome-guided transcriptome assembly from RNA-seq reads based on the model of splice graph. An extension of our program CLASS, CLASS2 jointly optimizes read patterns and the number of supporting reads to score and prioritize transcripts, implemented in a novel, scalable and efficient dynamic programming algorithm. When compared against reference programs, CLASS2 had the best overall accuracy and could detect up to twice as many splicing events with precision similar to the best reference program. Notably, it was the only tool to produce consistently reliable transcript models for a wide range of applications and sequencing strategies, including ribosomal RNA-depleted samples. Lightweight and multi-threaded, CLASS2 requires 〈3GB RAM and can analyze a 350 million read set within hours, and can be widely applied to transcriptomics studies ranging from clinical RNA sequencing, to alternative splicing analyses, and to the annotation of new genomes.
    Keywords: Computational Methods, Genomics
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  • 65
    Publication Date: 2016-09-20
    Description: Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of ‘actionable’ mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing. We developed FACETS, an ASCN tool and open-source software with a broad application to whole genome, whole-exome, as well as targeted panel sequencing platforms. It is a fully integrated stand-alone pipeline that includes sequencing BAM file post-processing, joint segmentation of total- and allele-specific read counts, and integer copy number calls corrected for tumor purity, ploidy and clonal heterogeneity, with comprehensive output and integrated visualization. We demonstrate the application of FACETS using The Cancer Genome Atlas (TCGA) whole-exome sequencing of lung adenocarcinoma samples. We also demonstrate its application to a clinical sequencing platform based on a targeted gene panel.
    Keywords: Computational Methods, Genomics
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  • 66
    Publication Date: 2016-09-03
    Description: We present SWAN, a statistical framework for robust detection of genomic structural variants in next-generation sequencing data and an analysis of mid-range size insertion and deletions (〈10 Kb) for whole genome analysis and DNA mixtures. To identify these mid-range size events, SWAN collectively uses information from read-pair, read-depth and one end mapped reads through statistical likelihoods based on Poisson field models. SWAN also uses soft-clip/split read remapping to supplement the likelihood analysis and determine variant boundaries. The accuracy of SWAN is demonstrated by in silico spike-ins and by identification of known variants in the NA12878 genome. We used SWAN to identify a series of novel set of mid-range insertion/deletion detection that were confirmed by targeted deep re-sequencing. An R package implementation of SWAN is open source and freely available.
    Keywords: Computational Methods, Genomics
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  • 67
    Publication Date: 2016-08-20
    Description: High-throughput screening (HTS) is an indispensable tool for drug (target) discovery that currently lacks user-friendly software tools for the robust identification of putative hits from HTS experiments and for the interpretation of these findings in the context of systems biology. We developed HiTSeekR as a one-stop solution for chemical compound screens, siRNA knock-down and CRISPR/Cas9 knock-out screens, as well as microRNA inhibitor and -mimics screens. We chose three use cases that demonstrate the potential of HiTSeekR to fully exploit HTS screening data in quite heterogeneous contexts to generate novel hypotheses for follow-up experiments: (i) a genome-wide RNAi screen to uncover modulators of TNFα, (ii) a combined siRNA and miRNA mimics screen on vorinostat resistance and (iii) a small compound screen on KRAS synthetic lethality. HiTSeekR is publicly available at http://hitseekr.compbio.sdu.dk . It is the first approach to close the gap between raw data processing, network enrichment and wet lab target generation for various HTS screen types.
    Keywords: Computational Methods, Genomics
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  • 68
    Publication Date: 2015-04-21
    Description: Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free ( de novo ) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.
    Keywords: Computational Methods, Genomics
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  • 69
    Publication Date: 2015-04-21
    Description: Distinguishing between promoter-like sequences in bacteria that belong to true or abortive promoters, or to those that do not initiate transcription at all, is one of the important challenges in transcriptomics. To address this problem, we have studied the genome-reduced bacterium Mycoplasma pneumoniae , for which the RNAs associated with transcriptional start sites have been recently experimentally identified. We determined the contribution to transcription events of different genomic features: the –10, extended –10 and –35 boxes, the UP element, the bases surrounding the –10 box and the nearest-neighbor free energy of the promoter region. Using a random forest classifier and the aforementioned features transformed into scores, we could distinguish between true, abortive promoters and non-promoters with good –10 box sequences. The methods used in this characterization of promoters can be extended to other bacteria and have important applications for promoter design in bacterial genome engineering.
    Keywords: Computational Methods, Genomics
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  • 70
    Publication Date: 2015-04-21
    Description: MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods.
    Keywords: Computational Methods, Genomics
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  • 71
    Publication Date: 2015-09-30
    Description: In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a β-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource ( larva.gersteinlab.org ).
    Keywords: Computational Methods, Genomics
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  • 72
    Publication Date: 2016-01-30
    Description: Disease-gene identification is a challenging process that has multiple applications within functional genomics and personalized medicine. Typically, this process involves both finding genes known to be associated with the disease (through literature search) and carrying out preliminary experiments or screens (e.g. linkage or association studies, copy number analyses, expression profiling) to determine a set of promising candidates for experimental validation. This requires extensive time and monetary resources. We describe Beegle , an online search and discovery engine that attempts to simplify this process by automating the typical approaches. It starts by mining the literature to quickly extract a set of genes known to be linked with a given query, then it integrates the learning methodology of Endeavour (a gene prioritization tool) to train a genomic model and rank a set of candidate genes to generate novel hypotheses. In a realistic evaluation setup, Beegle has an average recall of 84% in the top 100 returned genes as a search engine, which improves the discovery engine by 12.6% in the top 5% prioritized genes. Beegle is publicly available at http://beegle.esat.kuleuven.be/ .
    Keywords: Computational Methods, Genomics
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  • 73
    Publication Date: 2016-01-30
    Description: Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non-trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large-scale data sets.
    Keywords: Computational Methods, Genomics
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  • 74
    Publication Date: 2016-03-01
    Description: Tumors are characterized by properties of genetic instability, heterogeneity, and significant oligoclonality. Elucidating this intratumoral heterogeneity is challenging but important. In this study, we propose a framework, BubbleTree, to characterize the tumor clonality using next generation sequencing (NGS) data. BubbleTree simultaneously elucidates the complexity of a tumor biopsy, estimating cancerous cell purity, tumor ploidy, allele-specific copy number, and clonality and represents this in an intuitive graph. We further developed a three-step heuristic method to automate the interpretation of the BubbleTree graph, using a divide-and-conquer strategy. In this study, we demonstrated the performance of BubbleTree with comparisons to similar commonly used tools such as THetA2, ABSOLUTE, AbsCN-seq and ASCAT, using both simulated and patient-derived data. BubbleTree outperformed these tools, particularly in identifying tumor subclonal populations and polyploidy. We further demonstrated BubbleTree's utility in tracking clonality changes from patients’ primary to metastatic tumor and dating somatic single nucleotide and copy number variants along the tumor clonal evolution. Overall, the BubbleTree graph and corresponding model is a powerful approach to provide a comprehensive spectrum of the heterogeneous tumor karyotype in human tumors. BubbleTree is R-based and freely available to the research community ( https://www.bioconductor.org/packages/release/bioc/html/BubbleTree.html ).
    Keywords: Computational Methods, Genomics
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  • 75
    Publication Date: 2015-12-02
    Description: Alu insertions have contributed to 〉11% of the human genome and ~30–35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means to reconstruct the full sequence of insertion events from Illumina paired end reads. Comparison with published calls obtained using PacBio long-reads indicates a false discovery rate below 5%, at the cost of reduced sensitivity due to the colocation of reference and non-reference repeats. We generate a highly accurate call set of 1614 completely assembled Alu variants from 53 samples from the Human Genome Diversity Project (HGDP) panel. We utilize the reconstructed alternative insertion haplotypes to genotype 1010 fully assembled insertions, obtaining 〉99% agreement with genotypes obtained by PCR. In our assembled sequences, we find evidence of premature insertion mechanisms and observe 5' truncation in 16% of Alu Ya5 and Alu Yb8 insertions. The sites of truncation coincide with stem-loop structures and SRP9/14 binding sites in the Alu RNA, implicating L1 ORF2p pausing in the generation of 5' truncations. Additionally, we identified variable Alu J and Alu S elements that likely arose due to non-retrotransposition mechanisms.
    Keywords: Computational Methods, Genomics
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  • 76
    Publication Date: 2015-03-14
    Description: Mutual information (MI), a quantity describing the nonlinear dependence between two random variables, has been widely used to construct gene regulatory networks (GRNs). Despite its good performance, MI cannot separate the direct regulations from indirect ones among genes. Although the conditional mutual information (CMI) is able to identify the direct regulations, it generally underestimates the regulation strength, i.e. it may result in false negatives when inferring gene regulations. In this work, to overcome the problems, we propose a novel concept, namely conditional mutual inclusive information (CMI2), to describe the regulations between genes. Furthermore, with CMI2, we develop a new approach, namely CMI2NI (CMI2-based network inference), for reverse-engineering GRNs. In CMI2NI, CMI2 is used to quantify the mutual information between two genes given a third one through calculating the Kullback–Leibler divergence between the postulated distributions of including and excluding the edge between the two genes. The benchmark results on the GRNs from DREAM challenge as well as the SOS DNA repair network in Escherichia coli demonstrate the superior performance of CMI2NI. Specifically, even for gene expression data with small sample size, CMI2NI can not only infer the correct topology of the regulation networks but also accurately quantify the regulation strength between genes. As a case study, CMI2NI was also used to reconstruct cancer-specific GRNs using gene expression data from The Cancer Genome Atlas (TCGA). CMI2NI is freely accessible at http://www.comp-sysbio.org/cmi2ni .
    Keywords: Computational Methods, Genomics
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  • 77
    Publication Date: 2015-04-02
    Description: High-throughput sequencing of DNA coding regions has become a common way of assaying genomic variation in the study of human diseases. Copy number variation (CNV) is an important type of genomic variation, but detecting and characterizing CNV from exome sequencing is challenging due to the high level of biases and artifacts. We propose CODEX, a normalization and CNV calling procedure for whole exome sequencing data. The Poisson latent factor model in CODEX includes terms that specifically remove biases due to GC content, exon capture and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based exome sequencing data. CODEX is compared to existing methods on a population analysis of HapMap samples from the 1000 Genomes Project, and shown to be more accurate on three microarray-based validation data sets. We further evaluate performance on 222 neuroblastoma samples with matched normals and focus on a well-studied rare somatic CNV within the ATRX gene. We show that the cross-sample normalization procedure of CODEX removes more noise than normalizing the tumor against the matched normal and that the segmentation procedure performs well in detecting CNVs with nested structures.
    Keywords: Computational Methods, Genomics
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  • 78
    Publication Date: 2015-01-10
    Description: Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/ .
    Keywords: Computational Methods, Genomics
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  • 79
    Publication Date: 2016-05-20
    Description: The cancer genome is abnormal genome, and the ability to monitor its sequence had undergone a technological revolution. Yet prognosis and diagnosis remain an expert-based decision, with only limited abilities to provide machine-based decisions. We introduce a heterogeneity-based method for stratifying and visualizing whole-genome sequencing (WGS) reads. This method uses the heterogeneity within WGS reads to markedly reduce the dimensionality of next-generation sequencing data; it is available through the tool HiBS (Heterogeneity-Based Subclassification) that allows cancer sample classification. We validated HiBS using 〉200 WGS samples from nine different cancer types from The Cancer Genome Atlas (TCGA). With HiBS, we show progress with two WGS related issues: (i) differentiation between normal (NB) and tumor (TP) samples based solely on the information structure of their WGS data, and (ii) identification of specific regions of chromosomal amplification/deletion and their association with tumor stage. By comparing results to those obtained through available WGS analyses tools, we demonstrate some of the novelties obtained by the approach implemented in HiBS and also show nearly perfect normal/tumor classification, used to identify known and unknown chromosomal aberrations. Finally, the HiBS index has been associated with breast cancer tumor stage.
    Keywords: Computational Methods, Genomics
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  • 80
    Publication Date: 2016-05-20
    Description: Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/ .
    Keywords: Computational Methods, Genomics
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  • 81
    Publication Date: 2016-05-20
    Description: Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3'UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions.
    Keywords: Computational Methods, Genomics
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  • 82
    Publication Date: 2016-05-20
    Description: Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest. Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well. Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration.
    Keywords: Computational Methods, Genomics
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  • 83
    Publication Date: 2016-04-08
    Description: CircRNAs are novel members of the non-coding RNA family. For several decades circRNAs have been known to exist, however only recently the widespread abundance has become appreciated. Annotation of circRNAs depends on sequencing reads spanning the backsplice junction and therefore map as non-linear reads in the genome. Several pipelines have been developed to specifically identify these non-linear reads and consequently predict the landscape of circRNAs based on deep sequencing datasets. Here, we use common RNAseq datasets to scrutinize and compare the output from five different algorithms; circRNA_finder, find_circ, CIRCexplorer, CIRI, and MapSplice and evaluate the levels of bona fide and false positive circRNAs based on RNase R resistance. By this approach, we observe surprisingly dramatic differences between the algorithms specifically regarding the highly expressed circRNAs and the circRNAs derived from proximal splice sites. Collectively, this study emphasizes that circRNA annotation should be handled with care and that several algorithms should ideally be combined to achieve reliable predictions.
    Keywords: Computational Methods, Genomics
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  • 84
    Publication Date: 2016-03-19
    Description: Background: Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection. Results: Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation. Conclusion: Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates.
    Keywords: Computational Methods, Genomics
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  • 85
    Publication Date: 2016-03-19
    Description: Regulatory DNA elements, short genomic segments that regulate gene expression, have been implicated in developmental disorders and human disease. Despite this clinical urgency, only a small fraction of the regulatory DNA repertoire has been confirmed through reporter gene assays. The overall success rate of functional validation of candidate regulatory elements is low. Moreover, the number and diversity of datasets from which putative regulatory elements can be identified is large and rapidly increasing. We generated a flexible and user-friendly tool to integrate the information from different types of genomic datasets, e.g. ATAC-seq, ChIP-seq, conservation, aiming to increase the ease and success rate of functional prediction. To this end, we developed the EMERGE program that merges all datasets that the user considers informative and uses a logistic regression framework, based on validated functional elements, to set optimal weights to these datasets. ROC curve analysis shows that a combination of datasets leads to improved prediction of tissue-specific enhancers in human, mouse and Drosophila genomes. Functional assays based on this prediction can be expected to have substantially higher success rates. The resulting integrated signal for prediction of functional elements can be plotted in a build-in genome browser or exported for further analysis.
    Keywords: Computational Methods, Genomics
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  • 86
    Publication Date: 2016-03-19
    Description: Regulation of gene expression requires both transcription factor (TFs) and epigenetic modifications, and interplays between the two types of factors have been discovered. However study of relationships between chromatin features and TF–TF co-occupancy remains limited. Here, we revealed the relationship by first illustrating distinct profile patterns of chromatin features related to different binding events, including single TF binding and TF–TF co-occupancy of 71 TFs from five human cell lines. We further implemented statistical analyses to demonstrate the relationship by accurately predicting co-occupancy genome-widely using chromatin features including DNase I hypersensitivity, 11 histone modifications (HMs) and GC content. Remarkably, our results showed that the combination of chromatin features enables accurate predictions across the five cells. For individual chromatin features, DNase I enables high and consistent predictions. H3K27ac, H3K4me 2, H3K4me3 and H3K9ac are more reliable predictors than other HMs. Although the combination of 11 HMs achieves accurate predictions, their predictive ability varies considerably when a model obtained from one cell is applied to others, indicating relationship between HMs and TF–TF co-occupancy is cell type dependent. GC content is not a reliable predictor, but the addition of GC content to any other features enhances their predictive ability. Together, our results elucidate a strong relationship between TF–TF co-occupancy and chromatin features.
    Keywords: Computational Methods, Genomics
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  • 87
    Publication Date: 2016-03-19
    Description: The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co-localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover ‘functional 3D hotspots’, regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P -value contains MSB2 and ERG11 – known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k -Nearest Neighbor ( k -NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions.
    Keywords: Computational Methods, Genomics
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  • 88
    Publication Date: 2016-03-19
    Description: Hidden Markov models (HMMs) have been extensively used to dissect the genome into functionally distinct regions using data such as RNA expression or DNA binding measurements. It is a challenge to disentangle processes occurring on complementary strands of the same genomic region. We present the double-stranded HMM (dsHMM), a model for the strand-specific analysis of genomic processes. We applied dsHMM to yeast using strand specific transcription data, nucleosome data, and protein binding data for a set of 11 factors associated with the regulation of transcription.The resulting annotation recovers the mRNA transcription cycle (initiation, elongation, termination) while correctly predicting strand-specificity and directionality of the transcription process. We find that pre-initiation complex formation is an essentially undirected process, giving rise to a large number of bidirectional promoters and to pervasive antisense transcription. Notably, 12% of all transcriptionally active positions showed simultaneous activity on both strands. Furthermore, dsHMM reveals that antisense transcription is specifically suppressed by Nrd1, a yeast termination factor.
    Keywords: Computational Methods, Genomics
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  • 89
    Publication Date: 2016-03-19
    Description: Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) is widely used to identify binding sites for a target protein in the genome. An important scientific application is to identify changes in protein binding between different treatment conditions, i.e. to detect differential binding. This can reveal potential mechanisms through which changes in binding may contribute to the treatment effect. The csaw package provides a framework for the de novo detection of differentially bound genomic regions. It uses a window-based strategy to summarize read counts across the genome. It exploits existing statistical software to test for significant differences in each window. Finally, it clusters windows into regions for output and controls the false discovery rate properly over all detected regions. The csaw package can handle arbitrarily complex experimental designs involving biological replicates. It can be applied to both transcription factor and histone mark datasets, and, more generally, to any type of sequencing data measuring genomic coverage. csaw performs favorably against existing methods for de novo DB analyses on both simulated and real data. csaw is implemented as a R software package and is freely available from the open-source Bioconductor project.
    Keywords: Computational Methods, Genomics
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  • 90
    Publication Date: 2016-03-19
    Description: Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of micro-evolution. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method's wide applicability by testing it on multiple cases of micro-evolution. We show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens.
    Keywords: Computational Methods, Genomics
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  • 91
    Publication Date: 2016-05-06
    Description: An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.
    Keywords: Computational Methods, Genomics
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  • 92
    Publication Date: 2016-04-08
    Description: Small non-coding RNAs play a key role in many physiological and pathological processes. Since 2004, miRNA sequences have been catalogued in miRBase, which is currently in its 21st version. We investigated sequence and structural features of miRNAs annotated in the miRBase and compared them between different versions of this reference database. We have identified that the two most recent releases (v20 and v21) are influenced by next-generation sequencing based miRNA predictions and show significant deviation from miRNAs discovered prior to the high-throughput profiling period. From the analysis of miRBase, we derived a set of key characteristics to predict new miRNAs and applied the implemented algorithm to evaluate novel blood-borne miRNA candidates. We carried out 705 individual whole miRNA sequencings of blood cells and collected a total of 9.7 billion reads. Using miRDeep2 we initially predicted 1452 potentially novel miRNAs. After excluding false positives, 518 candidates remained. These novel candidates were ranked according to their distance to the features in the early miRBase versions allowing for an easier selection of a subset of putative miRNAs for validation. Selected candidates were successfully validated by qRT-PCR and northern blotting. In addition, we implemented a web-server for ranking potential miRNA candidates, which is available at: www.ccb.uni-saarland.de/novomirank .
    Keywords: Computational Methods, Genomics
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  • 93
    Publication Date: 2016-04-21
    Description: The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.
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  • 94
    Publication Date: 2016-04-21
    Description: The contribution of different mechanisms to the regulation of gene expression varies for different tissues and tumors. Complementation of predicted mRNA–miRNA and gene–transcription factor (TF) relationships with the results of expression correlation analyses derived for specific tumor types outlines the interactions with functional impact in the current biomaterial. We developed CrossHub software, which enables two-way identification of most possible TF–gene interactions: on the basis of ENCODE ChIP-Seq binding evidence or Jaspar prediction and co-expression according to the data of The Cancer Genome Atlas (TCGA) project, the largest cancer omics resource. Similarly, CrossHub identifies mRNA–miRNA pairs with predicted or validated binding sites (TargetScan, mirSVR, PicTar, DIANA microT, miRTarBase) and strong negative expression correlations. We observed partial consistency between ChIP-Seq or miRNA target predictions and gene–TF/miRNA co-expression, demonstrating a link between these indicators. Additionally, CrossHub expression-methylation correlation analysis can be used to identify hypermethylated CpG sites or regions with the greatest potential impact on gene expression. Thus, CrossHub is capable of outlining molecular portraits of a specific gene and determining the three most common sources of expression regulation: promoter/enhancer methylation, miRNA interference and TF-mediated activation or repression. CrossHub generates formatted Excel workbooks with the detailed results. CrossHub is freely available at https://sourceforge.net/projects/crosshub/ .
    Keywords: Computational Methods, Genomics
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  • 95
    Publication Date: 2016-08-20
    Description: Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR (Ensemble Cell Lineage Analysis with Improved Robustness), a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
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  • 96
    Publication Date: 2016-09-20
    Description: The quantification of transcriptomic features is the basis of the analysis of RNA-seq data. We present an integrated alignment workflow and a simple counting-based approach to derive estimates for gene, exon and exon–exon junction expression. In contrast to previous counting-based approaches, EQP takes into account only reads whose alignment pattern agrees with the splicing pattern of the features of interest. This leads to improved gene expression estimates as well as to the generation of exon counts that allow disambiguating reads between overlapping exons. Unlike other methods that quantify skipped introns, EQP offers a novel way to compute junction counts based on the agreement of the read alignments with the exons on both sides of the junction, thus providing a uniformly derived set of counts. We evaluated the performance of EQP on both simulated and real Illumina RNA-seq data and compared it with other quantification tools. Our results suggest that EQP provides superior gene expression estimates and we illustrate the advantages of EQP's exon and junction counts. The provision of uniformly derived high-quality counts makes EQP an ideal quantification tool for differential expression and differential splicing studies. EQP is freely available for download at https://github.com/Novartis/EQP-cluster .
    Keywords: Computational Methods, Genomics
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  • 97
    Publication Date: 2016-09-20
    Description: We describe Boiler, a new software tool for compressing and querying large collections of RNA-seq alignments. Boiler discards most per-read data, keeping only a genomic coverage vector plus a few empirical distributions summarizing the alignments. Since most per-read data is discarded, storage footprint is often much smaller than that achieved by other compression tools. Despite this, the most relevant per-read data can be recovered; we show that Boiler compression has only a slight negative impact on results given by downstream tools for isoform assembly and quantification. Boiler also allows the user to pose fast and useful queries without decompressing the entire file. Boiler is free open source software available from github.com/jpritt/boiler .
    Keywords: Computational Methods, Genomics
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  • 98
    Publication Date: 2016-10-14
    Description: Annotation of herpesvirus genomes has traditionally been undertaken through the detection of open reading frames and other genomic motifs, supplemented with sequencing of individual cDNAs. Second generation sequencing and high-density microarray studies have revealed vastly greater herpesvirus transcriptome complexity than is captured by existing annotation. The pervasive nature of overlapping transcription throughout herpesvirus genomes, however, poses substantial problems in resolving transcript structures using these methods alone. We present an approach that combines the unique attributes of Pacific Biosciences Iso-Seq long-read, Illumina short-read and deepCAGE (Cap Analysis of Gene Expression) sequencing to globally resolve polyadenylated isoform structures in replicating Epstein-Barr virus (EBV). Our method, Transcriptome Resolution through Integration of Multi-platform Data (TRIMD), identifies nearly 300 novel EBV transcripts, quadrupling the size of the annotated viral transcriptome. These findings illustrate an array of mechanisms through which EBV achieves functional diversity in its relatively small, compact genome including programmed alternative splicing (e.g. across the IR1 repeats), alternative promoter usage by LMP2 and other latency-associated transcripts, intergenic splicing at the BZLF2 locus, and antisense transcription and pervasive readthrough transcription throughout the genome.
    Keywords: Computational Methods, Genomics
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  • 99
    Publication Date: 2016-10-14
    Description: Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiE, 3'E and Ed, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 100
    Publication Date: 2016-12-01
    Description: Module identification is a frequently used approach for mining local structures with more significance in global networks. Recently, a wide variety of bilayer networks are emerging to characterize the more complex biological processes. In the light of special topological properties of bilayer networks and the accompanying challenges, there is yet no effective method aiming at bilayer module identification to probe the modular organizations from the more inspiring bilayer networks. To this end, we proposed the pseudo-3D clustering algorithm, which starts from extracting initial non-hierarchically organized modules and then iteratively deciphers the hierarchical organization of modules according to a bottom-up strategy. Specifically, a modularity function for bilayer modules was proposed to facilitate the algorithm reporting the optimal partition that gives the most accurate characterization of the bilayer network. Simulation studies demonstrated its robustness and outperformance against alternative competing methods. Specific applications to both the soybean and human miRNA-gene bilayer networks demonstrated that the pseudo-3D clustering algorithm successfully identified the overlapping, hierarchically organized and highly cohesive bilayer modules. The analyses on topology, functional and human disease enrichment and the bilayer subnetwork involved in soybean fat biosynthesis provided both the theoretical and biological evidence supporting the effectiveness and robustness of pseudo-3D clustering algorithm.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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