ALBERT

Description: Author Posting. © American Meteorological Society, 2022. 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 52(4), (2022): 597–616, https://doi.org/10.1175/jpo-d-21-0121.1.

Description: We provide a first-principles analysis of the energy fluxes in the oceanic internal wave field. The resulting formula is remarkably similar to the renowned phenomenological formula for the turbulent dissipation rate in the ocean, which is known as the finescale parameterization. The prediction is based on the wave turbulence theory of internal gravity waves and on a new methodology devised for the computation of the associated energy fluxes. In the standard spectral representation of the wave energy density, in the two-dimensional vertical wavenumber–frequency (m–ω) domain, the energy fluxes associated with the steady state are found to be directed downscale in both coordinates, closely matching the finescale parameterization formula in functional form and in magnitude. These energy transfers are composed of a “local” and a “scale-separated” contributions; while the former is quantified numerically, the latter is dominated by the induced diffusion process and is amenable to analytical treatment. Contrary to previous results indicating an inverse energy cascade from high frequency to low, at odds with observations, our analysis of all nonzero coefficients of the diffusion tensor predicts a direct energy cascade. Moreover, by the same analysis fundamental spectra that had been deemed “no-flux” solutions are reinstated to the status of “constant-downscale-flux” solutions. This is consequential for an understanding of energy fluxes, sources, and sinks that fits in the observational paradigm of the finescale parameterization, solving at once two long-standing paradoxes that had earned the name of “oceanic ultraviolet catastrophe.”

Description: The authors gratefully acknowledge support from the ONR Grant N00014-17-1-2852. YL gratefully acknowledges support from NSF DMS Award 2009418.

Description: 2022-09-25

Description: Author Posting. © American Meteorological Society, 2022. 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 52(8), (2022): 1593-1611, https://doi.org/10.1175/jpo-d-21-0180.1.

Description: This study presents novel observational estimates of turbulent dissipation and mixing in a standing meander between the Southeast Indian Ridge and the Macquarie Ridge in the Southern Ocean. By applying a finescale parameterization on the temperature, salinity, and velocity profiles collected from Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats in the upper 1600 m, we estimated the intensity and spatial distribution of dissipation rate and diapycnal mixing along the float tracks and investigated the sources. The indirect estimates indicate strong spatial and temporal variability of turbulent mixing varying from O(10−6) to O(10−3) m2 s−1 in the upper 1600 m. Elevated turbulent mixing is mostly associated with the Subantarctic Front (SAF) and mesoscale eddies. In the upper 500 m, enhanced mixing is associated with downward-propagating wind-generated near-inertial waves as well as the interaction between cyclonic eddies and upward-propagating internal waves. In the study region, the local topography does not play a role in turbulent mixing in the upper part of the water column, which has similar values in profiles over rough and smooth topography. However, both remotely generated internal tides and lee waves could contribute to the upward-propagating energy. Our results point strongly to the generation of turbulent mixing through the interaction of internal waves and the intense mesoscale eddy field.

Description: The observations were funded through grants from the Australian Research Council Discovery Project (DP170102162) and Australia’s Marine National Facility. Surface drifters were provided by Dr. Shaun Dolk of the Global Drifter Program. AC was supported by an Australian Research Council Postdoctoral Fellowship. AC, HEP, and NLB acknowledge support from the Australian Government Department of the Environment and Energy National Environmental Science Program and the ARC Centre of Excellence in Climate Extremes. KP acknowledges the support from the National Science Foundation.

Description: Author Posting. © American Meteorological Society, 2022. 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 52(1),(2022): 75–97, https://doi.org/10.1175/JPO-D-21-0099.1.

Description: Mesoscale eddies contain the bulk of the ocean’s kinetic energy (KE), but fundamental questions remain on the cross-scale KE transfers linking eddy generation and dissipation. The role of submesoscale flows represents the key point of discussion, with contrasting views of submesoscales as either a source or a sink of mesoscale KE. Here, the first observational assessment of the annual cycle of the KE transfer between mesoscale and submesoscale motions is performed in the upper layers of a typical open-ocean region. Although these diagnostics have marginal statistical significance and should be regarded cautiously, they are physically plausible and can provide a valuable benchmark for model evaluation. The cross-scale KE transfer exhibits two distinct stages, whereby submesoscales energize mesoscales in winter and drain mesoscales in spring. Despite this seasonal reversal, an inverse KE cascade operates throughout the year across much of the mesoscale range. Our results are not incompatible with recent modeling investigations that place the headwaters of the inverse KE cascade at the submesoscale, and that rationalize the seasonality of mesoscale KE as an inverse cascade-mediated response to the generation of submesoscales in winter. However, our findings may challenge those investigations by suggesting that, in spring, a downscale KE transfer could dampen the inverse KE cascade. An exploratory appraisal of the dynamics governing mesoscale–submesoscale KE exchanges suggests that the upscale KE transfer in winter is underpinned by mixed layer baroclinic instabilities, and that the downscale KE transfer in spring is associated with frontogenesis. Current submesoscale-permitting ocean models may substantially understate this downscale KE transfer, due to the models’ muted representation of frontogenesis.

Description: The OSMOSIS experiment was funded by the U.K. Natural Environment Research Council (NERC) through Grants NE/1019999/1 and NE/101993X/1. ACNG acknowledges the support of the Royal Society and the Wolfson Foundation, and XY that of a China Scholarship Council PhD studentship.

Description: Author Posting. © American Meteorological Society, 2022. 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 the Atmospheric and Oceanic Technology 39(4), (2022): 491–502, https://doi.org/10.1175/jtech-d-21-0046.1.

Description: The Air-Launched Autonomous Micro Observer (ALAMO) is a versatile profiling float that can be launched from an aircraft to make temperature and salinity observations of the upper ocean for over a year with high temporal sampling. Similar in dimensions and weight to an airborne expendable bathythermograph (AXBT), but with the same capability as Argo profiling floats, ALAMOs can be deployed from an A-sized (sonobuoy) launch tube, the stern ramp of a cargo plane, or the door of a small aircraft. Unlike an AXBT, however, the ALAMO float directly measures pressure, can incorporate additional sensors, and is capable of performing hundreds of ocean profiles compared to the single temperature profile provided by an AXBT. Upon deployment, the float parachutes to the ocean, releases the air-deployment package, and immediately begins profiling. Ocean profile data along with position and engineering information are transmitted via the Iridium satellite network, automatically processed, and then distributed by the Global Telecommunications System for use by the operational forecasting community. The ALAMO profiling mission can be modified using the two-way Iridium communications to change the profiling frequency and depth. Example observations are included to demonstrate the ALAMO’s utility.

Description: This work was supported by the National Oceanographic and Atmospheric Administration under Grants NA13OAR4830233 (as part of CINAR Sandy Supplemental funding from the Disaster Relief Appropriations Act of 2013) and NA14OAR4320158 and by Office of Naval Research under Grants N0001416WX01384, N0001416WX01262, and N000141512293. ALAMO floats are commercially available from MRV Systems, LLC (https://www.mrvsys.com).

Description: Author Posting. © American Meteorological Society, 2022. 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 the Atmospheric and Oceanic Technology 39(5), (2022): 595–617, https://doi.org/10.1175/jtech-d-21-0039.1.

Description: The future Surface Water and Ocean Topography (SWOT) mission aims to map sea surface height (SSH) in wide swaths with an unprecedented spatial resolution and subcentimeter accuracy. The instrument performance needs to be verified using independent measurements in a process known as calibration and validation (Cal/Val). The SWOT Cal/Val needs in situ measurements that can make synoptic observations of SSH field over an O(100) km distance with an accuracy matching the SWOT requirements specified in terms of the along-track wavenumber spectrum of SSH error. No existing in situ observing system has been demonstrated to meet this challenge. A field campaign was conducted during September 2019–January 2020 to assess the potential of various instruments and platforms to meet the SWOT Cal/Val requirement. These instruments include two GPS buoys, two bottom pressure recorders (BPR), three moorings with fixed conductivity–temperature–depth (CTD) and CTD profilers, and a glider. The observations demonstrated that 1) the SSH (hydrostatic) equation can be closed with 1–3 cm RMS residual using BPR, CTD mooring and GPS SSH, and 2) using the upper-ocean steric height derived from CTD moorings enable subcentimeter accuracy in the California Current region during the 2019/20 winter. Given that the three moorings are separated at 10–20–30 km distance, the observations provide valuable information about the small-scale SSH variability associated with the ocean circulation at frequencies ranging from hourly to monthly in the region. The combined analysis sheds light on the design of the SWOT mission postlaunch Cal/Val field campaign.

Description: The research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). All authors are supported by the SWOT project. J. T. Farrar was partially supported by NASA NNX16AH76G.

Description: 2022-11-01

Description: Author Posting. © American Meteorological Society, 2022. 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 52(6), (2022): 1233-1244, https://doi.org/10.1175/jpo-d-21-0223.1.

Description: The Sverdrup relation is the backbone of wind-driven circulation theory; it is a simple relation between the meridional transport of the wind-driven circulation in the upper ocean and the wind stress curl. However, the relation is valid for steady circulation only. In this study, a time-dependent Sverdrup relation is postulated, in which the meridional transport in a time-dependent circulation is the sum of the local wind stress curl term and a time-delayed term representing the effect of the eastern boundary condition. As an example, this time-dependent Sverdrup relation is evaluated through its application to the equatorial circulation in the Indian Ocean, using reanalysis data and a reduced gravity model. Close examination reveals that the southward Somali Current occurring during boreal winter is due to the combination of the local wind stress curl in the Arabian Sea and delayed signals representing the time change of layer thickness at the eastern boundary.

Description: This work is supported by NSFC (41822602, 41976016, 42005035, 42076021), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB42000000, XDA 20060502), Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (GML2019ZD0306), Guangdong Basic and Applied Basic Research Foundation (2021A1515011534), Youth Innovation Promotion Association CAS, ISEE2021ZD01, and LTOZZ2002. The numerical simulation is supported by the High-Performance Computing Division in the South China Sea Institute of Oceanology.

Description: 2022-11-27

Description: Author Posting. © American Meteorological Society, 2022. 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 52(12), (2022): 2923–2933, https://doi.org/10.1175/jpo-d-22-0064.1.

Description: The characteristics and dynamics of depth-average along-shelf currents at monthly and longer time scales are examined using 17 years of observations from the Martha’s Vineyard Coastal Observatory on the southern New England inner shelf. Monthly averages of the depth-averaged along-shelf current are almost always westward, with the largest interannual variability in winter. There is a consistent annual cycle with westward currents of 5 cm s−1 in summer decreasing to 1–2 cm s−1 in winter. Both the annual cycle and interannual variability in the depth-average along-shelf current are predominantly driven by the along-shelf wind stress. In the absence of wind forcing, there is a westward flow of ∼5 cm s−1 throughout the year. At monthly time scales, the depth-average along-shelf momentum balance is primarily between the wind stress, surface gravity wave–enhanced bottom stress, and an opposing pressure gradient that sets up along the southern New England shelf in response to the wind. Surface gravity wave enhancement of bottom stress is substantial over the inner shelf and is essential to accurately estimating the bottom stress variation across the inner shelf.

Description: The National Science Foundation, Woods Hole Oceanographic Institution, the Massachusetts Technology Collaborative, and the Office of Naval Research have supported the construction and maintenance of MVCO. The analysis presented here was partially funded by the National Science Foundation under Grants OCE 1558874 and OCE 1655686.

Description: Author Posting. © American Meteorological Society, 2022. 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 52(7), (2022): 1415–1430. https://doi.org/10.1175/JPO-D-21-0147.1.

Description: Strong subinertial variability near a seamount at the Xisha Islands in the South China Sea was revealed by mooring observations from January 2017 to January 2018. The intraseasonal deep flows presented two significant frequency bands, with periods of 9–20 and 30–120 days, corresponding to topographic Rossby waves (TRWs) and deep eddies, respectively. The TRW and deep eddy signals explained approximately 60% of the kinetic energy of the deep subinertial currents. The TRWs at the Ma, Mb, and Mc moorings had 297, 262, and 274 m vertical trapping lengths, and ∼43, 38, and 55 km wavelengths, respectively. Deep eddies were independent from the upper layer, with the largest temperature anomaly being 〉0.4°C. The generation of the TRWs was induced by mesoscale perturbations in the upper layer. The interaction between the cyclonic–anticyclonic eddy pair and the seamount topography contributed to the generation of deep eddies. Owing to the potential vorticity conservation, the westward-propagating tilted interface across the eddy pair squeezed the deep-water column, thereby giving rise to negative vorticity west of the seamount. The strong front between the eddy pair induced a northward deep flow, thereby generating a strong horizontal velocity shear because of lateral friction and enhanced negative vorticity. Approximately 4 years of observations further confirmed the high occurrence of TRWs and deep eddies. TRWs and deep eddies might be crucial for deep mixing near rough topographies by transferring mesoscale energy to small scales.

Description: This work was supported by the National Natural Science Foundation of China (92158204, 91958202, 42076019, 41776036, 91858203), the Open Project Program of State Key Laboratory of Tropical Oceanography (project LTOZZ2001), and Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (GML2019ZD0304).

Description: 2022-12-16

Description: Author Posting. © American Meteorological Society, 2022. 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 52(8), (2022): 1927-1943, https://doi.org/10.1175/jpo-d-21-0124.1.

Description: The Galápagos Archipelago lies on the equator in the path of the eastward flowing Pacific Equatorial Undercurrent (EUC). When the EUC reaches the archipelago, it upwells and bifurcates into a north and south branch around the archipelago at a latitude determined by topography. Since the Coriolis parameter (f) equals zero at the equator, strong velocity gradients associated with the EUC can result in Ertel potential vorticity (Q) having sign opposite that of planetary vorticity near the equator. Observations collected by underwater gliders deployed just west of the Galápagos Archipelago during 2013–16 are used to estimate Q and to diagnose associated instabilities that may impact the Galápagos Cold Pool. Estimates of Q are qualitatively conserved along streamlines, consistent with the 2.5-layer, inertial model of the EUC by Pedlosky. The Q with sign opposite of f is advected south of the Galápagos Archipelago when the EUC core is located south of the bifurcation latitude. The horizontal gradient of Q suggests that the region between 2°S and 2°N above 100 m is barotropically unstable, while limited regions are baroclinically unstable. Conditions conducive to symmetric instability are observed between the EUC core and the equator and within the southern branch of the undercurrent. Using 2-month and 3-yr averages, e-folding time scales are 2–11 days, suggesting that symmetric instability can persist on those time scales.

Description: This work was supported by the National Science Foundation (Grants OCE-1232971 and OCE-1233282), the NASA Earth and Space Science Fellowship Program (Grant 80NSSC17K0443), and the Global Ocean Monitoring and Observing Program of the National Oceanographic and Atmospheric Administration (NA13OAR4830216). Color maps are from Thyng et al. (2016).

Description: 2023-02-01

Description: Author Posting. © American Meteorological Society, 2022. 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 the Atmospheric and Oceanic Technology 39(8), (2022): 1183-1198, https://doi.org/10.1175/jtech-d-21-0068.1.

Description: Horizontal kinematic properties, such as vorticity, divergence, and lateral strain rate, are estimated from drifter clusters using three approaches. At submesoscale horizontal length scales O(1–10)km, kinematic properties become as large as planetary vorticity f, but challenging to observe because they evolve on short time scales O(hourstodays). By simulating surface drifters in a model flow field, we quantify the sources of uncertainty in the kinematic property calculations due to the deformation of cluster shape. Uncertainties arise primarily due to (i) violation of the linear estimation methods and (ii) aliasing of unresolved scales. Systematic uncertainties (iii) due to GPS errors, are secondary but can become as large as (i) and (ii) when aspect ratios are small. Ideal cluster parameters (number of drifters, length scale, and aspect ratio) are determined and error functions estimated empirically and theoretically. The most robust method—a two-dimensional, linear least squares fit—is applied to the first few days of a drifter dataset from the Bay of Bengal. Application of the length scale and aspect-ratio criteria minimizes errors (i) and (ii), and reduces the total number of clusters and so computational cost. The drifter-estimated kinematic properties map out a cyclonic mesoscale eddy with a surface, submesoscale fronts at its perimeter. Our analyses suggest methodological guidance for computing the two-dimensional kinematic properties in submesoscale flows, given the recently increasing quantity and quality of drifter observations, while also highlighting challenges and limitations.

Description: This research was supported by the Office of Naval Research (ONR) Departmental Research Initiative ASIRI under Grant N00014-13-1-0451 (SE and AM) and Grant N00014-13-1-0477 (VH and LC). The authors thank the captain and crew of the R/V Roger Revelle, and Andrew Lucas with the Multiscale Ocean Dynamics group at the Scripps Institution for Oceanography for providing the FastCTD data collected in 2015, which was supported by ONR Grant N00014-13-1-0489, as well as Eric D’Asaro for helpful discussions and Lance Braasch for assistance with the drifter dataset. AM and SE further thank NSF (Grant OCE-I434788) and ONR (Grant N00014-16-1-2470) for support. VH and LC were additionally supported by ONR Grants N00014-15-1-2286, N00014-14-1-0183, N00014-19-1-26-91 and NOAA Global Drifter Program (GDP) Grant NA15OAR4320071.

Description: 2023-02-01

Description: Author Posting. © American Meteorological Society, 2020. 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 50(9), (2020): 2491-2506, doi:10.1175/JPO-D-20-0056.1.

Description: An idealized two-layer shallow water model is applied to the study of the dynamics of the Arctic Ocean halocline. The model is forced by a surface stress distribution reflective of the observed wind stress pattern and ice motion and by an inflow representing the flow of Pacific Water through Bering Strait. The model reproduces the main elements of the halocline circulation: an anticyclonic Beaufort Gyre in the western basin (representing the Canada Basin), a cyclonic circulation in the eastern basin (representing the Eurasian Basin), and a Transpolar Drift between the two gyres directed from the upwind side of the basin to the downwind side of the basin. Analysis of the potential vorticity budget shows a basin-averaged balance primarily between potential vorticity input at the surface and dissipation at the lateral boundaries. However, advection is a leading-order term not only within the anticyclonic and cyclonic gyres but also between the gyres. This means that the eastern and western basins are dynamically connected through the advection of potential vorticity. Both eddy and mean fluxes play a role in connecting the regions of potential vorticity input at the surface with the opposite gyre and with the viscous boundary layers. These conclusions are based on a series of model runs in which forcing, topography, straits, and the Coriolis parameter were varied.

Description: This study was supported by National Science Foundation Grant OPP-1822334. Comments and suggestions from two anonymous referees greatly helped to improve the paper.

Description: 2021-02-17

Description: Author Posting. © American Meteorological Society, 2020. 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 50(11), (2020): 3235–3251, https://doi.org/10.1175/JPO-D-20-0095.1.

Description: The dense outflow through Denmark Strait is the largest contributor to the lower limb of the Atlantic meridional overturning circulation, yet a description of the full velocity field across the strait remains incomplete. Here we analyze a set of 22 shipboard hydrographic–velocity sections occupied along the Látrabjarg transect at the Denmark Strait sill, obtained over the time period 1993–2018. The sections provide the first complete view of the kinematic components at the sill: the shelfbreak East Greenland Current (EGC), the combined flow of the separated EGC, and the North Icelandic Jet (NIJ), and the northward-flowing North Icelandic Irminger Current (NIIC). The total mean transport of overflow water is 3.54 ± 0.29 Sv (1 Sv ≡ 106 m3 s−1), comparable to previous estimates. The dense overflow is partitioned in terms of water mass constituents and flow components. The mean transports of the two types of overflow water—Atlantic-origin Overflow Water and Arctic-origin Overflow Water—are comparable in Denmark Strait, while the merged NIJ–separated EGC transports 55% more water than the shelfbreak EGC. A significant degree of water mass exchange takes place between the branches as they converge in Denmark Strait. There are two dominant time-varying configurations of the flow that are characterized as a cyclonic state and a noncyclonic state. These appear to be wind-driven. A potential vorticity analysis indicates that the flow through Denmark Strait is subject to symmetric instability. This occurs at the top of the overflow layer, implying that the mixing/entrainment process that modifies the overflow water begins at the sill.

Description: Funding for the study was provided by National Science Foundation (NSF) Grants OCE-1259618, OCE-1756361, and OCE-1558742. The German research cruises were financially supported through various EU Projects (e.g. THOR, NACLIM) and national projects (most recently TRR 181 “Energy Transfer in Atmosphere and Ocean” funded by the German Research Foundation and RACE II “Regional Atlantic Circulation and Global Change” funded by the German Federal Ministry for Education and Research). GWKM acknowledges the support of the Natural Sciences and Engineering Research Council of Canada. LP was supported by NSF Grant OCE-1657870.

Description: Author Posting. © American Meteorological Society, 2020. 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 33(17), (2020): 7697-7714, https://doi.org/10.1175/JCLI-D-20-0115.1.

Description: The decadal to multidecadal mixed layer variability is investigated in a region south of the Kuroshio Extension (130°E–180°, 25°–35°N), an area where the North Pacific subtropical mode water forms, during 1948–2012. By analyzing the mixed layer heat budget with different observational and reanalysis data, here we show that the decadal to multidecadal variability of the mixed layer temperature and mixed layer depth is covaried with the Atlantic multidecadal oscillation (AMO), instead of the Pacific decadal oscillation (PDO). The mixed layer temperature has strong decadal to multidecadal variability, being warm before 1970 and after 1990 (AMO positive phase) and cold during 1970–90 (AMO negative phase), and so does the mixed layer depth. The dominant process for the mixed layer temperature decadal to multidecadal variability is the Ekman advection, which is controlled by the zonal wind changes related to the AMO. The net heat flux into the ocean surface Qnet acts as a damping term and it is mainly from the effect of latent heat flux and partially from sensible heat flux. While the wind as well as mixed layer temperature decadal changes related to the PDO are weak in the western Pacific Ocean. Our finding proposes the possible influence of the AMO on the northwestern Pacific Ocean mixed layer variability, and could be a potential predictor for the decadal to multidecadal climate variability in the western Pacific Ocean.

Description: Xiaopei Lin is supported by the China’s national key research and development projects (2016YFA0601803) and the National Natural Science Foundation of China (41925025 and U1606402). Baolan Wu is supported by the China Scholarship Council (201806330010). Lisan Yu thanks NOAA for support for her study on climate change and variability.

Description: Author Posting. © American Meteorological Society, 2021. 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 51(8),(2021): 2425–2441, https://doi.org/10.1175/JPO-D-20-0317.1.

Description: The frequency and latitudinal dependence of the midlatitude wind-driven meridional overturning circulation (MOC) is studied using theory and linear and nonlinear applications of a quasigeostrophic numerical model. Wind forcing is varied either by changing the strength of the wind or by shifting the meridional location of the wind stress curl pattern. At forcing periods of less than the first-mode baroclinic Rossby wave basin crossing time scale, the linear response in the middepth and deep ocean is in phase and opposite to the Ekman transport. For forcing periods that are close to the Rossby wave basin crossing time scale, the upper and deep MOC are enhanced, and the middepth MOC becomes phase shifted, relative to the Ekman transport. At longer forcing periods the deep MOC weakens and the middepth MOC increases, but eventually for long enough forcing periods (decadal) the entire wind-driven MOC spins down. Nonlinearities and mesoscale eddies are found to be important in two ways. First, baroclinic instability causes the middepth MOC to weaken, lose correlation with the Ekman transport, and lose correlation with the MOC in the opposite gyre. Second, eddy thickness fluxes extend the MOC beyond the latitudes of direct wind forcing. These results are consistent with several recent studies describing the four-dimensional structure of the MOC in the North Atlantic Ocean.

Description: This study was supported by National Science Foundation Grant OCE-1947290.

Description: 2022-01-13

Description: Author Posting. © American Meteorological Society, 2020. 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 50(9), (2020): 2669-2688, doi:10.1175/JPO-D-19-0077.1

Description: The scale-dependent variance of tracer properties in the ocean bears the imprint of the oceanic eddy field. Anomalies in spice (which combines anomalies in temperature T and salinity S on isopycnal surfaces) act as passive tracers beneath the surface mixed layer (ML). We present an analysis of spice distributions along isopycnals in the upper 200 m of the ocean, calculated with over 9000 vertical profiles of T and S measured along ~4800 km of ship tracks in the Bay of Bengal. The data are from three separate research cruises—in the winter monsoon season of 2013 and in the late and early summer monsoon seasons of 2015 and 2018. We present a spectral analysis of horizontal tracer variance statistics on scales ranging from the submesoscale (~1 km) to the mesoscale (~100 km). Isopycnal layers that are closer to the ML-base exhibit redder spectra of tracer variance at scales ≲10 km than is predicted by theories of quasigeostrophic turbulence or frontogenesis. Two plausible explanations are postulated. The first is that stirring by submesoscale motions and shear dispersion by near-inertial waves enhance effective horizontal mixing and deplete tracer variance at horizontal scales ≲10 km in this region. The second is that the spice anomalies are coherent with dynamical properties such as potential vorticity, and not interpretable as passively stirred.

Description: We are grateful to the captain and crew of the R/V Roger Revelle and the R/V Thomas G. Thompson, and all ASIRI-OMM and MISO-BOB scientists. We thank Prof. Andrew Thompson and an anonymous reviewer for suggestions that improved the manuscript. This work was carried out under the Office of Naval Research’s Air-Sea Interaction Regional Initiative (ASIRI) and Monsoon Intra-Seasonal Oscillations in the Bay of Bengal (MISO-BOB) research initiatives, in collaboration with the Indian Ministry of Earth Science’s Ocean Mixing and Monsoons (OMM) initiative supported by the Monsoon Mission. Support came from ONR Grants N00014-16-1-2470, N00014-13-1-0451, N00014-17-1-2390 (G.S.J. and A.M.), N00014-14-1-0455 (J.M. and J.N), N00014-17-1-2511 (J.M.), N00014-13-1-0489, N00014-17-1-2391 (A.L.), N00014-15-1-2634 (E.S.), N00014-13-1-0456, N00014-17-1-2355 (A.T.), and N00014-13-1-0453, N00014-17-1-2880 (J.F.).

Description: 2021-02-28

Description: Author Posting. © American Meteorological Society, 2019. 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 49(7), (2019): 1889-1904, doi:10.1175/JPO-D-19-0053.1.

Description: A high-resolution numerical model, together with in situ and satellite observations, is used to explore the nature and dynamics of the dominant high-frequency (from one day to one week) variability in Denmark Strait. Mooring measurements in the center of the strait reveal that warm water “flooding events” occur, whereby the North Icelandic Irminger Current (NIIC) propagates offshore and advects subtropical-origin water northward through the deepest part of the sill. Two other types of mesoscale processes in Denmark Strait have been described previously in the literature, known as “boluses” and “pulses,” associated with a raising and lowering of the overflow water interface. Our measurements reveal that flooding events occur in conjunction with especially pronounced pulses. The model indicates that the NIIC hydrographic front is maintained by a balance between frontogenesis by the large-scale flow and frontolysis by baroclinic instability. Specifically, the temperature and salinity tendency equations demonstrate that the eddies act to relax the front, while the mean flow acts to sharpen it. Furthermore, the model reveals that the two dense water processes—boluses and pulses (and hence flooding events)—are dynamically related to each other and tied to the meandering of the hydrographic front in the strait. Our study thus provides a general framework for interpreting the short-time-scale variability of Denmark Strait Overflow Water entering the Irminger Sea.

Description: MAS was supported by the National Science Foundation (NSF) under Grants OCE-1558742 and OCE-1534618. RSP, PL, and DM were supported by NSF under Grants OCE-1558742 and OCE-1259618. WJvA was supported by the Helmholtz Infrastructure Initiative FRAM. TWNH and MA were supported by NSF under Grants OCE-1633124 and OCE-118123.

Description: 2020-07-01

Description: Author Posting. © American Meteorological Society, 2018. 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 48 (2018): 643-646, doi:10.1175/JPO-D-17-0240.1.

Description: A simple oceanic model is presented for source–sink flow on the β plane to discuss the pathways from source to sink when transport boundary layers have large enough Reynolds numbers to be inertial in their dynamics. A representation of the flow as a Fofonoff gyre, suggested by prior work on inertial boundary layers and eddy-driven circulations in two-dimensional turbulent flows, indicates that even when the source and sink are aligned along the same western boundary the flow must intrude deep into the interior before exiting at the sink. The existence of interior pathways for the flow is thus an intrinsic property of an inertial circulation and is not dependent on particular geographical basin geometry.

Description: 2018-09-12

Description: Author Posting. © American Meteorological Society, 2018. 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 31 (2018): 4847-4863, doi:10.1175/JCLI-D-17-0802.1.

Description: The sensitivity of sea ice to the temperature of inflowing Atlantic water across the Greenland–Scotland Ridge is investigated using an eddy-resolving configuration of the Massachusetts Institute of Technology General Circulation Model with idealized topography. During the last glacial period, when climate on Greenland is known to have been extremely unstable, sea ice is thought to have covered the Nordic seas. The dramatic excursions in climate during this period, seen as large abrupt warming events on Greenland and known as Dansgaard–Oeschger (DO) events, are proposed to have been caused by a rapid retreat of Nordic seas sea ice. Here, we show that a full sea ice cover and Arctic-like stratification can exist in the Nordic seas given a sufficiently cold Atlantic inflow and corresponding low transport of heat across the Greenland–Scotland Ridge. Once sea ice is established, continued sea ice formation and melt efficiently freshens the surface ocean and makes the deeper layers more saline. This creates a strong salinity stratification in the Nordic seas, similar to today’s Arctic Ocean, with a cold fresh surface layer protecting the overlying sea ice from the warm Atlantic water below. There is a nonlinear response in Nordic seas sea ice to Atlantic water temperature with simulated large abrupt changes in sea ice given small changes in inflowing temperature. This suggests that the DO events were more likely to have occurred during periods of reduced warm Atlantic water inflow to the Nordic seas.

Description: The research was supported by the Centre for Climate Dynamics at the Bjerknes Centre for Climate Research. The research leading to these results is part of the ice2ice project funded by the European Research Council under the European Community Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement 610055.

Description: Author Posting. © American Meteorological Society, 2018. 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 48 (2018): 163-174, doi:10.1175/JPO-D-17-0161.1.

Description: The general problem of exchange from a shallow shelf across sharp topography to the deep ocean forced by narrow, cross-shelf wind jets is studied using quasigeostrophic theory and an idealized primitive equation numerical model. Interest is motivated by katabatic winds that emanate from narrow fjords in southeast Greenland, although similar topographically constrained wind jets are found throughout the world’s oceans. Because there is no net vorticity input by the wind, the circulation is largely confined to the region near the forcing. Circulation over the shelf is limited by bottom friction for weakly stratified flows, but stratification allows for much stronger upper-layer flows that are regulated by weak coupling to the lower layer. Over the sloping topography, the topographic beta effect limits the deep flow, while, for sufficient stratification, the upper-layer flow can cross the topography to connect the shelf to the open ocean. This can be an effective transport mechanism even for short, strong wind events because damping of the upper-layer flow is weak. A variety of transients are generated for an abrupt onset of winds, including short topography Rossby waves, long topographic Rossby waves, and inertial waves. Using parameters representative of southeast Greenland, katabatic wind events will force an offshore transport of O(0.4) Sv (1 Sv ≡ 106 m3 s−1) that, when considered for 2 days, will result in an offshore flux of O(5 × 1010) m3.

Description: MAS was supported by the National Science Foundation under Grant OCE-1533170.

Description: 2018-07-18

Description: Author Posting. © American Meteorological Society, 2018. 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 48 (2018): 1375-1384, doi:10.1175/JPO-D-17-0266.1.

Description: The relationship between net mixing and the estuarine exchange flow may be quantified using a salinity variance budget. Here “mixing” is defined as the rate of destruction of volume-integrated salinity variance, and the exchange flow is quantified using the total exchange flow. These concepts are explored using an idealized 3D model estuary. It is shown that in steady state (e.g., averaging over the spring–neap cycle) the volume-integrated mixing is approximately given by Mixing ≅ SinSoutQr, where Sin and Sout are the representative salinities of in- and outflowing layers at the mouth and Qr is the river volume flux. This relationship provides an extension of the familiar Knudsen relation, in which the exchange flow is diagnosed based on knowledge of these same three quantities, quantitatively linking mixing to the exchange flow.

Description: The work was supported by the National Science Foundation through Grants OCE-1736242 to PM and OCE-1736539 to WRG and by the German Research Foundation through Grants TRR 181 and GRK 2000 to HB.

Description: Author Posting. © American Meteorological Society, 2017. 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 30 (2017): 1739-1751, doi:10.1175/JCLI-D-16-0200.1.

Description: The Indian Ocean has sustained robust surface warming in recent decades, but the role of multidecadal variability remains unclear. Using ocean model hindcasts, characteristics of low-frequency Indian Ocean temperature variations are explored. Simulated upper-ocean temperature changes across the Indian Ocean in the hindcast are consistent with those recorded in observational products and ocean reanalyses. Indian Ocean temperatures exhibit strong warming trends since the 1950s limited to the surface and south of 30°S, while extensive subsurface cooling occurs over much of the tropical Indian Ocean. Previous work focused on diagnosing causes of these long-term trends in the Indian Ocean over the second half of the twentieth century. Instead, the temporal evolution of Indian Ocean subsurface heat content is shown here to reveal distinct multidecadal variations associated with the Pacific decadal oscillation, and the long-term trends are thus interpreted to result from aliasing of the low-frequency variability. Transmission of the multidecadal signal occurs via an oceanic pathway through the Indonesian Throughflow and is manifest across the Indian Ocean centered along 12°S as westward-propagating Rossby waves modulating thermocline and subsurface heat content variations. Resulting low-frequency changes in the eastern Indian Ocean thermocline depth are associated with decadal variations in the frequency of Indian Ocean dipole (IOD) events, with positive IOD events unusually common in the 1960s and 1990s with a relatively shallow thermocline. In contrast, the deeper thermocline depth in the 1970s and 1980s is associated with frequent negative IOD and rare positive IOD events. Changes in Pacific wind forcing in recent decades and associated rapid increases in Indian Ocean subsurface heat content can thus affect the basin’s leading mode of variability, with implications for regional climate and vulnerable societies in surrounding countries.

Description: This research was supported by a Research Fellowship by the Alexander von Humboldt Foundation, as well as the Ocean Climate Change Institute and the Investment in Science Fund at WHOI.

Description: 2017-08-15

Description: Author Posting. © American Meteorological Society, 2017. 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 47 (2017): 2251-2265, doi:10.1175/JPO-D-17-0042.1.

Description: The problem of localized dense water formation over a sloping bottom is considered for the general case in which the topography forms a closed contour. This class of problems is motivated by topography around islands or shallow shoals in which convection resulting from brine rejection or surface heat loss reaches the bottom. The focus of this study is on the large-scale circulation that is forced far from the region of surface forcing. The authors find that a cyclonic current is generated around the topography, in the opposite sense to the propagation of the dense water plume. In physical terms, this current results from the propagation of low sea surface height from the region of dense water formation anticyclonically along the topographic contours back to the formation region. This pressure gradient is then balanced by a cyclonic geostrophic flow. This basic structure is well predicted by a linear quasigeostrophic theory, a primitive equation model, and in rotating tank experiments. For sufficiently strong forcing, the anticyclonic circulation of the dense plume meets this cyclonic circulation to produce a sharp front and offshore advection of dense water at the bottom and buoyant water at the surface. This nonlinear limit is demonstrated in both the primitive equation model and in the tank experiments.

Description: MAS was supported by the National Science Foundation under Grant OCE-1534618. Support for CC was given by the WHOI Ocean Climate Change Institute Proposal 27071273.

Description: 2018-03-20

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): 8317-8331, doi:10.1175/JCLI-D-16-0109.1.

Description: A simple analytic model is developed to represent the offshore decay of cold sea surface temperature (SST) signals that originate from wind-driven upwelling at a coastal boundary. The model couples an oceanic mixed layer to an atmospheric boundary layer through wind stress and air–sea heat exchange. The primary mechanism that controls SST is a balance between Ekman advection and air–sea exchange. The offshore penetration of the cold SST signal decays exponentially with a length scale that is the product of the ocean Ekman velocity and a time scale derived from the air–sea heat flux and the radiative balance in the atmospheric boundary layer. This cold SST signal imprints on the atmosphere in terms of both the boundary layer temperature and surface wind. Nonlinearities due to the feedback between SST and atmospheric wind, baroclinic instability, and thermal wind in the atmospheric boundary layer all slightly modify this linear theory. The decay scales diagnosed from two-dimensional and three-dimensional eddy-resolving numerical ocean models are in close agreement with the theory, demonstrating that the basic physics represented by the theory remain dominant even in these more complete systems. Analysis of climatological SST off the west coast of the United States also shows a decay of the cold SST anomaly with scale roughly in agreement with the theory.

Description: MASwas supported by the Andrew W. Mellon Foundation Endowed Fund for Innovative Research and the National Science Foundation under Grant OCE-1433170 and PLR-1415489. NS was supported by the National Aeronautics and Space Administration under Grant NNX14AL83G, the Department of Energy, Office of Science Grant DE-SC0006766, and the Japan Agency for Marine-Earth Science and Technology as part of the JAMSTEC-IPRC Joint Investigations.

Description: 2017-05-03

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

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

Description: © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PeerJ 4 (2016): e1839, doi:10.7717/peerj.1839.

Description: High-throughput sequencing provides a fast and cost-effective mean to recover genomes of organisms from all domains of life. However, adequate curation of the assembly results against potential contamination of non-target organisms requires advanced bioinformatics approaches and practices. Here, we re-analyzed the sequencing data generated for the tardigrade Hypsibius dujardini, and created a holistic display of the eukaryotic genome assembly using DNA data originating from two groups and eleven sequencing libraries. By using bacterial single-copy genes, k-mer frequencies, and coverage values of scaffolds we could identify and characterize multiple near-complete bacterial genomes from the raw assembly, and curate a 182 Mbp draft genome for H. dujardini supported by RNA-Seq data. Our results indicate that most contaminant scaffolds were assembled from Moleculo long-read libraries, and most of these contaminants have differed between library preparations. Our re-analysis shows that visualization and curation of eukaryotic genome assemblies can benefit from tools designed to address the needs of today’s microbiologists, who are constantly challenged by the difficulties associated with the identification of distinct microbial genomes in complex environmental metagenomes.

Description: This work was supported by the Frank R. Lillie Research Innovation Award, and startup funds from the University of Chicago.

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

Description: Chromosome-long haplotyping of human genomes is important to identify genetic variants with differing gene expression, in human evolution studies, clinical diagnosis, and other biological and medical fields. Although several methods have realized haplotyping based on sequencing technologies or population statistics, accuracy and cost are factors that prohibit their wide use. Borrowing ideas from group testing theories, we proposed a clone-based haplotyping method by overlapping pool sequencing. The clones from a single individual were pooled combinatorially and then sequenced. According to the distinct pooling pattern for each clone in the overlapping pool sequencing, alleles for the recovered variants could be assigned to their original clones precisely. Subsequently, the clone sequences could be reconstructed by linking these alleles accordingly and assembling them into haplotypes with high accuracy. To verify the utility of our method, we constructed 130 110 clones in silico for the individual NA12878 and simulated the pooling and sequencing process. Ultimately, 99.9% of variants on chromosome 1 that were covered by clones from both parental chromosomes were recovered correctly, and 112 haplotype contigs were assembled with an N50 length of 3.4 Mb and no switch errors. A comparison with current clone-based haplotyping methods indicated our method was more accurate.

Description: Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these ‘repressed transcripts’ have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies.

Description: Identifying large-scale structural variation in cancer genomes continues to be a challenge to researchers. Current methods rely on genome alignments based on a reference that can be a poor fit to highly variant and complex tumor genomes. To address this challenge we developed a method that uses available breakpoint information to generate models of structural variations. We use these models as references to align previously unmapped and discordant reads from a genome. By using these models to align unmapped reads, we show that our method can help to identify large-scale variations that have been previously missed.

Description: Advanced sequencing technologies have generated a plethora of data for many chromatin marks in multiple tissues and cell types, yet there is lack of a generalized tool for optimal utility of those data. A major challenge is to quantitatively model the epigenetic dynamics across both the genome and many cell types for understanding their impacts on differential gene regulation and disease. We introduce IDEAS, an i ntegrative and d iscriminative e pigenome a nnotation s ystem, for jointly characterizing epigenetic landscapes in many cell types and detecting differential regulatory regions. A key distinction between our method and existing state-of-the-art algorithms is that IDEAS integrates epigenomes of many cell types simultaneously in a way that preserves the position-dependent and cell type-specific information at fine scales, thereby greatly improving segmentation accuracy and producing comparable annotations across cell types.

Description: A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 x 10 –4 insertions per genome per generation and the rate of IS homologous recombination is 4.5 x 10 –5 recombinations per genome per generation. These events are mostly contributed by the IS elements IS 1 , IS 2 , IS 5 and IS 186 . Spatial analysis of new insertions suggest that transposition is biased to proximal insertions, and the length spectrum of IS-caused deletions is largely explained by local hopping. For any of the ISs studied there is no region of the circular genome that is favored or disfavored for new insertions but there are notable hotspots for deletions. Some elements have preferences for non-coding sequence or for the beginning and end of coding regions, largely explained by target site motifs. Interestingly, transposition and deletion rates remain constant across the wild-type and 12 mutant E. coli lines, each deficient in a distinct DNA repair pathway. Finally, we characterized the target sites of four IS families, confirming previous results and characterizing a highly specific pattern at IS 186 target-sites, 5'-GGGG(N6/N7)CCCC-3'. We also detected 48 long deletions not involving IS elements.

Description: Genetic variants in or near miRNA genes can have profound effects on miRNA expression and targeting. As user-friendly software for the impact prediction of miRNA variants on a large scale is still lacking, we created a tool called miRVaS. miRVaS automates this prediction by annotating the location of the variant relative to functional regions within the miRNA hairpin (seed, mature, loop, hairpin arm, flanks) and by annotating all predicted structural changes within the miRNA due to the variant. In addition, the tool defines the most important region that is predicted to have structural changes and calculates a conservation score that is indicative of the reliability of the structure prediction. The output is presented in a tab-separated file, which enables fast screening, and in an html file, which allows visual comparison between wild-type and variant structures. All separate images are provided for downstream use. Finally, we tested two different approaches on a small test set of published functionally validated genetic variants for their capacity to predict the impact of variants on miRNA expression.

Description: Analysis of RNA-seq data often detects numerous ‘non-co-linear’ (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts ( trans -spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method (‘NCLscan’), which utilized a stepwise alignment strategy to almost completely eliminate false calls (〉98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans -spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans -spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome.

Description: Visualization of chromosomal dynamics is important for understanding many fundamental intra-nuclear processes. Efficient and reliable live-cell multicolor labeling of chromosomal loci can realize this goal. However, the current methods are constrained mainly by insufficient labeling throughput, efficiency, flexibility as well as photostability. Here we have developed a new approach to realize dual-color chromosomal loci imaging based on a modified single-guide RNA (sgRNA) of the CRISPR/Cas9 system. The modification of sgRNA was optimized by structure-guided engineering of the original sgRNA, consisting of RNA aptamer insertions that bind fluorescent protein-tagged effectors. By labeling and tracking telomeres, centromeres and genomic loci, we demonstrate that the new approach is easy to implement and enables robust dual-color imaging of genomic elements. Importantly, our data also indicate that the fast exchange rate of RNA aptamer binding effectors makes our sgRNA-based labeling method much more tolerant to photobleaching than the Cas9-based labeling method. This is crucial for continuous, long-term tracking of chromosomal dynamics. Lastly, as our method is complementary to other live-cell genomic labeling systems, it is therefore possible to combine them into a plentiful palette for the study of native chromatin organization and genome ultrastructure dynamics in living cells.

Description: Presence of excess unaltered, wild-type (WT) DNA providing no information of biological or clinical value often masks rare alterations containing diagnostic or therapeutic clues in cancer, prenatal diagnosis, infectious diseases or organ transplantation. With the surge of high-throughput technologies there is a growing demand for removing unaltered DNA over large pools-of-sequences. Here we present nuclease-assisted minor-allele enrichment with probe-overlap (NaME-PrO), a single-step approach with broad genome coverage that can remove WT-DNA from numerous sequences simultaneously, prior to genomic analysis. NaME-PrO employs a double-strand-DNA-specific nuclease and overlapping oligonucleotide-probes interrogating WT-DNA targets and guiding nuclease digestion to these sites. Mutation-containing DNA creates probe-DNA mismatches that inhibit digestion, thus subsequent DNA-amplification magnifies DNA-alterations at all selected targets. We demonstrate several-hundred-fold mutation enrichment in diverse human samples on multiple clinically relevant targets including tumor samples and circulating DNA in 50-plex reactions. Enrichment enables routine mutation detection at 0.01% abundance while by adjusting conditions it is possible to sequence mutations down to 0.00003% abundance, or to scan tumor-suppressor genes for rare mutations. NaME-PrO introduces a simple and highly parallel process to remove un-informative DNA sequences and unmask clinically and biologically useful alterations.

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 5;533(7601):7. doi: 10.1038/533007a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27146996" target="_blank"〉PubMed〈/a〉

Description: Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Mark A -- Burda, Joshua E -- Ren, Yilong -- Ao, Yan -- O'Shea, Timothy M -- Kawaguchi, Riki -- Coppola, Giovanni -- Khakh, Baljit S -- Deming, Timothy J -- Sofroniew, Michael V -- MH099559A/MH/NIMH NIH HHS/ -- MH104069/MH/NIMH NIH HHS/ -- NS057624/NS/NINDS NIH HHS/ -- NS060677/NS/NINDS NIH HHS/ -- NS084030/NS/NINDS NIH HHS/ -- P30 NS062691/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Apr 14;532(7598):195-200. doi: 10.1038/nature17623. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1763, USA. ; Departments of Psychiatry and Neurology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1761, USA. ; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1751, USA. ; Departments of Bioengineering, Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095-1600, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027288" target="_blank"〉PubMed〈/a〉

Description: The origin of eukaryotes stands as a major conundrum in biology. Current evidence indicates that the last eukaryotic common ancestor already possessed many eukaryotic hallmarks, including a complex subcellular organization. In addition, the lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Mitochondria are ubiquitous organelles derived from an alphaproteobacterial endosymbiont. Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote. Most competing scenarios can be roughly grouped into either mito-early, which consider the driving force of eukaryogenesis to be mitochondrial endosymbiosis into a simple host, or mito-late, which postulate that a significant complexity predated mitochondrial endosymbiosis. Here we provide evidence for late mitochondrial endosymbiosis. We use phylogenomics to directly test whether proto-mitochondrial proteins were acquired earlier or later than other proteins of the last eukaryotic common ancestor. We find that last eukaryotic common ancestor protein families of alphaproteobacterial ancestry and of mitochondrial localization show the shortest phylogenetic distances to their closest prokaryotic relatives, compared with proteins of different prokaryotic origin or cellular localization. Altogether, our results shed new light on a long-standing question and provide compelling support for the late acquisition of mitochondria into a host that already had a proteome of chimaeric phylogenetic origin. We argue that mitochondrial endosymbiosis was one of the ultimate steps in eukaryogenesis and that it provided the definitive selective advantage to mitochondria-bearing eukaryotes over less complex forms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780264/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780264/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pittis, Alexandros A -- Gabaldon, Toni -- England -- Nature. 2016 Mar 3;531(7592):101-4. doi: 10.1038/nature16941. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Carrer del Dr Aiguader, 88, 08003 Barcelona, Spain. ; Departament of Ciencies Experimentals I de La Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain. ; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Passeig de Lluis Companys 23, 08010 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26840490" target="_blank"〉PubMed〈/a〉

Description: The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused and dependent on ‘non-core’ portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity and reveals a novel role for the RAG1 non-core region in RAG1 targeting.

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

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

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

Description: Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information. Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples.

Description: Data on biological mechanisms of aging are mostly obtained from cross-sectional study designs. An inherent disadvantage of this design is that inter-individual differences can mask small but biologically significant age-dependent changes. A serially sampled design (same individual at different time points) would overcome this problem but is often limited by the relatively small numbers of available paired samples and the statistics being used. To overcome these limitations, we have developed a new vector-based approach, termed three-component analysis, which incorporates temporal distance, signal intensity and variance into one single score for gene ranking and is combined with gene set enrichment analysis. We tested our method on a unique age-based sample set of human skin fibroblasts and combined genome-wide transcription, DNA methylation and histone methylation (H3K4me3 and H3K27me3) data. Importantly, our method can now for the first time demonstrate a clear age-dependent decrease in expression of genes coding for proteins involved in translation and ribosome function. Using analogies with data from lower organisms, we propose a model where age-dependent down-regulation of protein translation-related components contributes to extend human lifespan.

Description: A major challenge in the field of shotgun metagenomics is the accurate identification of organisms present within a microbial community, based on classification of short sequence reads. Though existing microbial community profiling methods have attempted to rapidly classify the millions of reads output from modern sequencers, the combination of incomplete databases, similarity among otherwise divergent genomes, errors and biases in sequencing technologies, and the large volumes of sequencing data required for metagenome sequencing has led to unacceptably high false discovery rates (FDR). Here, we present the application of a novel, gene-independent and signature-based metagenomic taxonomic profiling method with significantly and consistently smaller FDR than any other available method. Our algorithm circumvents false positives using a series of non-redundant signature databases and examines G enomic O rigins T hrough T axonomic CHA llenge (GOTTCHA). GOTTCHA was tested and validated on 20 synthetic and mock datasets ranging in community composition and complexity, was applied successfully to data generated from spiked environmental and clinical samples, and robustly demonstrates superior performance compared with other available tools.

Description: With read lengths of currently up to 2 x 300 bp, high throughput and low sequencing costs Illumina's MiSeq is becoming one of the most utilized sequencing platforms worldwide. The platform is manageable and affordable even for smaller labs. This enables quick turnaround on a broad range of applications such as targeted gene sequencing, metagenomics, small genome sequencing and clinical molecular diagnostics. However, Illumina error profiles are still poorly understood and programs are therefore not designed for the idiosyncrasies of Illumina data. A better knowledge of the error patterns is essential for sequence analysis and vital if we are to draw valid conclusions. Studying true genetic variation in a population sample is fundamental for understanding diseases, evolution and origin. We conducted a large study on the error patterns for the MiSeq based on 16S rRNA amplicon sequencing data. We tested state-of-the-art library preparation methods for amplicon sequencing and showed that the library preparation method and the choice of primers are the most significant sources of bias and cause distinct error patterns. Furthermore we tested the efficiency of various error correction strategies and identified quality trimming (Sickle) combined with error correction (BayesHammer) followed by read overlapping (PANDAseq) as the most successful approach, reducing substitution error rates on average by 93%.

Description: RNA-seq is a sensitive and accurate technique to compare steady-state levels of RNA between different cellular states. However, as it does not provide an account of transcriptional activity per se , other technologies are needed to more precisely determine acute transcriptional responses. Here, we have developed an easy, sensitive and accurate novel computational method, iRNA-seq , for genome-wide assessment of transcriptional activity based on analysis of intron coverage from total RNA-seq data. Comparison of the results derived from iRNA-seq analyses with parallel results derived using current methods for genome-wide determination of transcriptional activity, i.e. global run-on (GRO)-seq and RNA polymerase II (RNAPII) ChIP-seq, demonstrate that iRNA-seq provides similar results in terms of number of regulated genes and their fold change. However, unlike the current methods that are all very labor-intensive and demanding in terms of sample material and technologies, iRNA-seq is cheap and easy and requires very little sample material. In conclusion, iRNA-seq offers an attractive novel alternative to current methods for determination of changes in transcriptional activity at a genome-wide level.

Description: Any given human individual carries multiple genetic variants that disrupt protein-coding genes, through structural variation, as well as nucleotide variants and indels. Predicting the phenotypic consequences of a gene disruption remains a significant challenge. Current approaches employ information from a range of biological networks to predict which human genes are haploinsufficient (meaning two copies are required for normal function) or essential (meaning at least one copy is required for viability). Using recently available study gene sets, we show that these approaches are strongly biased towards providing accurate predictions for well-studied genes. By contrast, we derive a haploinsufficiency score from a combination of unbiased large-scale high-throughput datasets, including gene co-expression and genetic variation in over 6000 human exomes. Our approach provides a haploinsufficiency prediction for over twice as many genes currently unassociated with papers listed in Pubmed as three commonly-used approaches, and outperforms these approaches for predicting haploinsufficiency for less-studied genes. We also show that fine-tuning the predictor on a set of well-studied ‘gold standard’ haploinsufficient genes does not improve the prediction for less-studied genes. This new score can readily be used to prioritize gene disruptions resulting from any genetic variant, including copy number variants, indels and single-nucleotide variants.

Description: Meta-analysis of gene expression has enabled numerous insights into biological systems, but current methods have several limitations. We developed a method to perform a meta-analysis using the elastic net, a powerful and versatile approach for classification and regression. To demonstrate the utility of our method, we conducted a meta-analysis of lung cancer gene expression based on publicly available data. Using 629 samples from five data sets, we trained a multinomial classifier to distinguish between four lung cancer subtypes. Our meta-analysis-derived classifier included 58 genes and achieved 91% accuracy on leave-one-study-out cross-validation and on three independent data sets. Our method makes meta-analysis of gene expression more systematic and expands the range of questions that a meta-analysis can be used to address. As the amount of publicly available gene expression data continues to grow, our method will be an effective tool to help distill these data into knowledge.

Description: Extensive and multi-dimensional data sets generated from recent cancer omics profiling projects have presented new challenges and opportunities for unraveling the complexity of cancer genome landscapes. In particular, distinguishing the unique complement of genes that drive tumorigenesis in each patient from a sea of passenger mutations is necessary for translating the full benefit of cancer genome sequencing into the clinic. We address this need by presenting a data integration framework (OncoIMPACT) to nominate patient-specific driver genes based on their phenotypic impact. Extensive in silico and in vitro validation helped establish OncoIMPACT's robustness, improved precision over competing approaches and verifiable patient and cell line specific predictions (2/2 and 6/7 true positives and negatives, respectively). In particular, we computationally predicted and experimentally validated the gene TRIM24 as a putative novel amplified driver in a melanoma patient. Applying OncoIMPACT to more than 1000 tumor samples, we generated patient-specific driver gene lists in five different cancer types to identify modes of synergistic action. We also provide the first demonstration that computationally derived driver mutation signatures can be overall superior to single gene and gene expression based signatures in enabling patient stratification and prognostication. Source code and executables for OncoIMPACT are freely available from http://sourceforge.net/projects/oncoimpact .

Description: Analysis of rewired upstream subnetworks impacting downstream differential gene expression aids the delineation of evolving molecular mechanisms. Cumulative statistics based on conventional differential correlation are limited for subnetwork rewiring analysis since rewiring is not necessarily equivalent to change in correlation coefficients. Here we present a computational method ChiNet to quantify subnetwork rewiring by statistical heterogeneity that enables detection of potential genotype changes causing altered transcription regulation in evolving organisms. Given a differentially expressed downstream gene set, ChiNet backtracks a rewired upstream subnetwork from a super-network including gene interactions known to occur under various molecular contexts. We benchmarked ChiNet for its high accuracy in distinguishing rewired artificial subnetworks, in silico yeast transcription-metabolic subnetworks, and rewired transcription subnetworks for Candida albicans versus Saccharomyces cerevisiae , against two differential-correlation based subnetwork rewiring approaches. Then, using transcriptome data from tolerant S. cerevisiae strain NRRL Y-50049 and a wild-type intolerant strain, ChiNet identified 44 metabolic pathways affected by rewired transcription subnetworks anchored to major adaptively activated transcription factor genes YAP1 , RPN4 , SFP1 and ROX1 , in response to toxic chemical challenges involved in lignocellulose-to-biofuels conversion. These findings support the use of ChiNet in rewiring analysis of subnetworks where differential interaction patterns resulting from divergent nonlinear dynamics abound.

Description: Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein–RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein–rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a ‘proof of concept’ that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites.

Description: The emergence of new sequencing technologies has facilitated the use of bacterial whole genome alignments for evolutionary studies and outbreak analyses. These datasets, of increasing size, often include examples of multiple different mechanisms of horizontal sequence transfer resulting in substantial alterations to prokaryotic chromosomes. The impact of these processes demands rapid and flexible approaches able to account for recombination when reconstructing isolates’ recent diversification. Gubbins is an iterative algorithm that uses spatial scanning statistics to identify loci containing elevated densities of base substitutions suggestive of horizontal sequence transfer while concurrently constructing a maximum likelihood phylogeny based on the putative point mutations outside these regions of high sequence diversity. Simulations demonstrate the algorithm generates highly accurate reconstructions under realistically parameterized models of bacterial evolution, and achieves convergence in only a few hours on alignments of hundreds of bacterial genome sequences. Gubbins is appropriate for reconstructing the recent evolutionary history of a variety of haploid genotype alignments, as it makes no assumptions about the underlying mechanism of recombination. The software is freely available for download at github.com/sanger-pathogens/Gubbins , implemented in Python and C and supported on Linux and Mac OS X.

Description: Genomic structural variation (SV), a common hallmark of cancer, has important predictive and therapeutic implications. However, accurately detecting SV using high-throughput sequencing data remains challenging, especially for ‘targeted’ resequencing efforts. This is critically important in the clinical setting where targeted resequencing is frequently being applied to rapidly assess clinically actionable mutations in tumor biopsies in a cost-effective manner. We present BreaKmer, a novel approach that uses a ‘kmer’ strategy to assemble misaligned sequence reads for predicting insertions, deletions, inversions, tandem duplications and translocations at base-pair resolution in targeted resequencing data. Variants are predicted by realigning an assembled consensus sequence created from sequence reads that were abnormally aligned to the reference genome. Using targeted resequencing data from tumor specimens with orthogonally validated SV, non-tumor samples and whole-genome sequencing data, BreaKmer had a 97.4% overall sensitivity for known events and predicted 17 positively validated, novel variants. Relative to four publically available algorithms, BreaKmer detected SV with increased sensitivity and limited calls in non-tumor samples, key features for variant analysis of tumor specimens in both the clinical and research settings.

Description: Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.

Description: Methods to interpret personal genome sequences are increasingly required. Here, we report a novel framework (EvoTol) to identify disease-causing genes using patient sequence data from within protein coding-regions. EvoTol quantifies a gene's intolerance to mutation using evolutionary conservation of protein sequences and can incorporate tissue-specific gene expression data. We apply this framework to the analysis of whole-exome sequence data in epilepsy and congenital heart disease, and demonstrate EvoTol's ability to identify known disease-causing genes is unmatched by competing methods. Application of EvoTol to the human interactome revealed networks enriched for genes intolerant to protein sequence variation, informing novel polygenic contributions to human disease.

Description: Detecting in vivo transcription factor (TF) binding is important for understanding gene regulatory circuitries. ChIP-seq is a powerful technique to empirically define TF binding in vivo . However, the multitude of distinct TFs makes genome-wide profiling for them all labor-intensive and costly. Algorithms for in silico prediction of TF binding have been developed, based mostly on histone modification or DNase I hypersensitivity data in conjunction with DNA motif and other genomic features. However, technical limitations of these methods prevent them from being applied broadly, especially in clinical settings. We conducted a comprehensive survey involving multiple cell lines, TFs, and methylation types and found that there are intimate relationships between TF binding and methylation level changes around the binding sites. Exploiting the connection between DNA methylation and TF binding, we proposed a novel supervised learning approach to predict TF–DNA interaction using data from base-resolution whole-genome methylation sequencing experiments. We devised beta-binomial models to characterize methylation data around TF binding sites and the background. Along with other static genomic features, we adopted a random forest framework to predict TF–DNA interaction. After conducting comprehensive tests, we saw that the proposed method accurately predicts TF binding and performs favorably versus competing methods.

Description: Plant genomes, and eukaryotic genomes in general, are typically repetitive, polyploid and heterozygous, which complicates genome assembly. The short read lengths of early Sanger and current next-generation sequencing platforms hinder assembly through complex repeat regions, and many draft and reference genomes are fragmented, lacking skewed GC and repetitive intergenic sequences, which are gaining importance due to projects like the Encyclopedia of DNA Elements (ENCODE). Here we report the whole-genome sequencing and assembly of the desiccation-tolerant grass Oropetium thomaeum. Using only single-molecule real-time sequencing, which generates long (〉16 kilobases) reads with random errors, we assembled 99% (244 megabases) of the Oropetium genome into 625 contigs with an N50 length of 2.4 megabases. Oropetium is an example of a 'near-complete' draft genome which includes gapless coverage over gene space as well as intergenic sequences such as centromeres, telomeres, transposable elements and rRNA clusters that are typically unassembled in draft genomes. Oropetium has 28,466 protein-coding genes and 43% repeat sequences, yet with 30% more compact euchromatic regions it is the smallest known grass genome. The Oropetium genome demonstrates the utility of single-molecule real-time sequencing for assembling high-quality plant and other eukaryotic genomes, and serves as a valuable resource for the plant comparative genomics community.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉VanBuren, Robert -- Bryant, Doug -- Edger, Patrick P -- Tang, Haibao -- Burgess, Diane -- Challabathula, Dinakar -- Spittle, Kristi -- Hall, Richard -- Gu, Jenny -- Lyons, Eric -- Freeling, Michael -- Bartels, Dorothea -- Ten Hallers, Boudewijn -- Hastie, Alex -- Michael, Todd P -- Mockler, Todd C -- England -- Nature. 2015 Nov 26;527(7579):508-11. doi: 10.1038/nature15714. Epub 2015 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donald Danforth Plant Science Center, St Louis, Missouri 63132, USA. ; Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, California 94720, USA. ; Department of Horticulture, Michigan State University, East Lansing, Michigan 48823, USA. ; iPlant Collaborative, School of Plant Sciences, University of Arizona, Tucson, Arizona 85721, USA. ; Center for Genomics and Biotechnology, Haixia Institute of Science and Technology (HIST), Fujian Agriculture and Forestry University, Fuzhou 350002, China. ; IMBIO, University of Bonn, Kirschallee 1, D-53115 Bonn, Germany. ; Pacific Biosciences, Menlo Park, California 94025, USA. ; BioNano Genomics, San Diego, California 92121, USA. ; Ibis Biosciences, Carlsbad, California 92008, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560029" target="_blank"〉PubMed〈/a〉

Description: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF 〈/= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755714/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755714/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Hou-Feng -- Forgetta, Vincenzo -- Hsu, Yi-Hsiang -- Estrada, Karol -- Rosello-Diez, Alberto -- Leo, Paul J -- Dahia, Chitra L -- Park-Min, Kyung Hyun -- Tobias, Jonathan H -- Kooperberg, Charles -- Kleinman, Aaron -- Styrkarsdottir, Unnur -- Liu, Ching-Ti -- Uggla, Charlotta -- Evans, Daniel S -- Nielson, Carrie M -- Walter, Klaudia -- Pettersson-Kymmer, Ulrika -- McCarthy, Shane -- Eriksson, Joel -- Kwan, Tony -- Jhamai, Mila -- Trajanoska, Katerina -- Memari, Yasin -- Min, Josine -- Huang, Jie -- Danecek, Petr -- Wilmot, Beth -- Li, Rui -- Chou, Wen-Chi -- Mokry, Lauren E -- Moayyeri, Alireza -- Claussnitzer, Melina -- Cheng, Chia-Ho -- Cheung, Warren -- Medina-Gomez, Carolina -- Ge, Bing -- Chen, Shu-Huang -- Choi, Kwangbom -- Oei, Ling -- Fraser, James -- Kraaij, Robert -- Hibbs, Matthew A -- Gregson, Celia L -- Paquette, Denis -- Hofman, Albert -- Wibom, Carl -- Tranah, Gregory J -- Marshall, Mhairi -- Gardiner, Brooke B -- Cremin, Katie -- Auer, Paul -- Hsu, Li -- Ring, Sue -- Tung, Joyce Y -- Thorleifsson, Gudmar -- Enneman, Anke W -- van Schoor, Natasja M -- de Groot, Lisette C P G M -- van der Velde, Nathalie -- Melin, Beatrice -- Kemp, John P -- Christiansen, Claus -- Sayers, Adrian -- Zhou, Yanhua -- Calderari, Sophie -- van Rooij, Jeroen -- Carlson, Chris -- Peters, Ulrike -- Berlivet, Soizik -- Dostie, Josee -- Uitterlinden, Andre G -- Williams, Stephen R -- Farber, Charles -- Grinberg, Daniel -- LaCroix, Andrea Z -- Haessler, Jeff -- Chasman, Daniel I -- Giulianini, Franco -- Rose, Lynda M -- Ridker, Paul M -- Eisman, John A -- Nguyen, Tuan V -- Center, Jacqueline R -- Nogues, Xavier -- Garcia-Giralt, Natalia -- Launer, Lenore L -- Gudnason, Vilmunder -- Mellstrom, Dan -- Vandenput, Liesbeth -- Amin, Najaf -- van Duijn, Cornelia M -- Karlsson, Magnus K -- Ljunggren, Osten -- Svensson, Olle -- Hallmans, Goran -- Rousseau, Francois -- Giroux, Sylvie -- Bussiere, Johanne -- Arp, Pascal P -- Koromani, Fjorda -- Prince, Richard L -- Lewis, Joshua R -- Langdahl, Bente L -- Hermann, A Pernille -- Jensen, Jens-Erik B -- Kaptoge, Stephen -- Khaw, Kay-Tee -- Reeve, Jonathan -- Formosa, Melissa M -- Xuereb-Anastasi, Angela -- Akesson, Kristina -- McGuigan, Fiona E -- Garg, Gaurav -- Olmos, Jose M -- Zarrabeitia, Maria T -- Riancho, Jose A -- Ralston, Stuart H -- Alonso, Nerea -- Jiang, Xi -- Goltzman, David -- Pastinen, Tomi -- Grundberg, Elin -- Gauguier, Dominique -- Orwoll, Eric S -- Karasik, David -- Davey-Smith, George -- AOGC Consortium -- Smith, Albert V -- Siggeirsdottir, Kristin -- Harris, Tamara B -- Zillikens, M Carola -- van Meurs, Joyce B J -- Thorsteinsdottir, Unnur -- Maurano, Matthew T -- Timpson, Nicholas J -- Soranzo, Nicole -- Durbin, Richard -- Wilson, Scott G -- Ntzani, Evangelia E -- Brown, Matthew A -- Stefansson, Kari -- Hinds, David A -- Spector, Tim -- Cupples, L Adrienne -- Ohlsson, Claes -- Greenwood, Celia M T -- UK10K Consortium -- Jackson, Rebecca D -- Rowe, David W -- Loomis, Cynthia A -- Evans, David M -- Ackert-Bicknell, Cheryl L -- Joyner, Alexandra L -- Duncan, Emma L -- Kiel, Douglas P -- Rivadeneira, Fernando -- Richards, J Brent -- G1000143/Medical Research Council/United Kingdom -- K01 AR062655/AR/NIAMS NIH HHS/ -- MC_UU_12013/3/Medical Research Council/United Kingdom -- R01 AG005394/AG/NIA NIH HHS/ -- R01 AG005407/AG/NIA NIH HHS/ -- R01 AG027574/AG/NIA NIH HHS/ -- R01 AG027576/AG/NIA NIH HHS/ -- R01 AR035582/AR/NIAMS NIH HHS/ -- R01 AR035583/AR/NIAMS NIH HHS/ -- RC2 AR058973/AR/NIAMS NIH HHS/ -- U01 AG018197/AG/NIA NIH HHS/ -- U01 AG042140/AG/NIA NIH HHS/ -- U01 AG042143/AG/NIA NIH HHS/ -- U01 AR045580/AR/NIAMS NIH HHS/ -- U01 AR045583/AR/NIAMS NIH HHS/ -- U01 AR045614/AR/NIAMS NIH HHS/ -- U01 AR045632/AR/NIAMS NIH HHS/ -- U01 AR045647/AR/NIAMS NIH HHS/ -- U01 AR045654/AR/NIAMS NIH HHS/ -- U01 AR066160/AR/NIAMS NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):112-7. doi: 10.1038/nature14878. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal H3A 1A2, Canada. ; Department of Medicine, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal H3T 1E2, Canada. ; Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts 02131, USA. ; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of MIT and Harvard, Boston, Massachusetts 02115, USA. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Developmental Biology Program, Sloan Kettering Institute, New York, New York 10065, USA. ; The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane 4102, Australia. ; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York 10065, USA. ; Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York 10021, USA. ; Rheumatology Divison, Hospital for Special Surgery New York, New York 10021, USA. ; School of Clinical Science, University of Bristol, Bristol BS10 5NB, UK. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; Department of Research, 23andMe, Mountain View, California 94041, USA. ; Department of Population Genomics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; California Pacific Medical Center Research Institute, San Francisco, California 94158, USA. ; Department of Public Health and Preventive Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Bone &Mineral Unit, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK. ; Departments of Pharmacology and Clinical Neurosciences, Umea University, Umea S-901 87, Sweden. ; Department of Public Health and Clinical Medicine, Umea University, Umea SE-901 87, Sweden. ; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; McGill University and Genome Quebec Innovation Centre, Montreal H3A 0G1, Canada. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Oregon Clinical and Translational Research Institute, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Department of Medical and Clinical Informatics, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Department of Human Genetics, McGill University, Montreal H3A 1B1, Canada. ; Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden 2300RC, The Netherlands. ; Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA. ; Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal H3G 1Y6, Canada. ; Department of Computer Science, Trinity University, San Antonio, Texas 78212, USA. ; Musculoskeletal Research Unit, University of Bristol, Bristol BS10 5NB, UK. ; Department of Radiation Sciences, Umea University, Umea S-901 87, Sweden. ; School of Public Health, University of Wisconsin, Milwaukee, Wisconsin 53726, USA. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; Department of Statistics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. ; Department of Human Nutrition, Wageningen University, Wageningen 6700 EV, The Netherlands. ; Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam 1105, The Netherlands. ; Nordic Bioscience, Herlev 2730, Denmark. ; Cordeliers Research Centre, INSERM UMRS 1138, Paris 75006, France. ; Institute of Cardiometabolism and Nutrition, University Pierre &Marie Curie, Paris 75013, France. ; Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Genetics, University of Barcelona, Barcelona 08028, Spain. ; U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona 28029, Spain. ; Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona 08028, Spain. ; Women's Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, California 92093, USA. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Osteoporosis &Bone Biology Program, Garvan Institute of Medical Research, Sydney 2010, Australia. ; School of Medicine Sydney, University of Notre Dame Australia, Sydney 6959, Australia. ; St. Vincent's Hospital &Clinical School, NSW University, Sydney 2010, Australia. ; Musculoskeletal Research Group, Institut Hospital del Mar d'Investigacions Mediques, Barcelona 08003, Spain. ; Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, 28029, Spain. ; Department of Internal Medicine, Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona 08193, Spain. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Icelandic Heart Association, Kopavogur IS-201, Iceland. ; Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland. ; Genetic epidemiology unit, Department of Epidemiology, Erasmus MC, Rotterdam 3000CA, The Netherlands. ; Department of Orthopaedics, Skane University Hospital Malmo 205 02, Sweden. ; Department of Medical Sciences, University of Uppsala, Uppsala 751 85, Sweden. ; Department of Surgical and Perioperative Sciences, Umea Unviersity, Umea 901 85, Sweden. ; Department of Molecular Biology, Medical Biochemistry and Pathology, Universite Laval, Quebec City G1V 0A6, Canada. ; Axe Sante des Populations et Pratiques Optimales en Sante, Centre de recherche du CHU de Quebec, Quebec City G1V 4G2, Canada. ; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands 6009, Australia. ; Department of Medicine, University of Western Australia, Perth 6009, Australia. ; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C 8000, Denmark. ; Department of Endocrinology, Odense University Hospital, Odense C 5000, Denmark. ; Department of Endocrinology, Hvidovre University Hospital, Hvidovre 2650, Denmark. ; Clinical Gerontology Unit, University of Cambridge, Cambridge CB2 2QQ, UK. ; Medicine and Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford OX3 7LD, UK. ; Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida MSD 2080, Malta. ; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmo, Lund University, 205 02, Sweden. ; Department of Medicine and Psychiatry, University of Cantabria, Santander 39011, Spain. ; Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander 39008, Spain. ; Department of Legal Medicine, University of Cantabria, Santander 39011, Spain. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. ; Department of Medicine and Physiology, McGill University, Montreal H4A 3J1, Canada. ; Department of Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 13010, Israel. ; Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. ; Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island 02903, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal H3A 1A2, Canada. ; Department of Oncology, Gerald Bronfman Centre, McGill University, Montreal H2W 1S6, Canada. ; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA. ; The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. ; Department of Diabetes and Endocrinology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367794" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marsh, Geoff -- England -- Nature. 2015 Feb 12;518(7538):147. doi: 10.1038/518147a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25673391" target="_blank"〉PubMed〈/a〉

Description: Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire. They have the largest nervous systems among the invertebrates and present other striking morphological innovations including camera-like eyes, prehensile arms, a highly derived early embryogenesis and a remarkably sophisticated adaptive colouration system. To investigate the molecular bases of cephalopod brain and body innovations, we sequenced the genome and multiple transcriptomes of the California two-spot octopus, Octopus bimaculoides. We found no evidence for hypothesized whole-genome duplications in the octopus lineage. The core developmental and neuronal gene repertoire of the octopus is broadly similar to that found across invertebrate bilaterians, except for massive expansions in two gene families previously thought to be uniquely enlarged in vertebrates: the protocadherins, which regulate neuronal development, and the C2H2 superfamily of zinc-finger transcription factors. Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions. We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system. Finally, we found evidence for large-scale genomic rearrangements that are closely associated with transposable element expansions. Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Albertin, Caroline B -- Simakov, Oleg -- Mitros, Therese -- Wang, Z Yan -- Pungor, Judit R -- Edsinger-Gonzales, Eric -- Brenner, Sydney -- Ragsdale, Clifton W -- Rokhsar, Daniel S -- R03 HD056094/HD/NICHD NIH HHS/ -- R03HD064887/HD/NICHD NIH HHS/ -- S10RR027303/RR/NCRR NIH HHS/ -- S10RR029668/RR/NCRR NIH HHS/ -- T32 HD055164/HD/NICHD NIH HHS/ -- UL1 TR000430/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Aug 13;524(7564):220-4. doi: 10.1038/nature14668.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 9040495, Japan [2] Centre for Organismal Studies, University of Heidelberg, 69117 Heidelberg, Germany. ; Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. ; Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 9040495, Japan [2] Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. ; Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 9040495, Japan. ; 1] Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA [2] Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 9040495, Japan [2] Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA [3] Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26268193" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2015 Oct 1;526(7571):5-6. doi: 10.1038/526005b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26432202" target="_blank"〉PubMed〈/a〉

Description: Kennewick Man, referred to as the Ancient One by Native Americans, is a male human skeleton discovered in Washington state (USA) in 1996 and initially radiocarbon dated to 8,340-9,200 calibrated years before present (BP). His population affinities have been the subject of scientific debate and legal controversy. Based on an initial study of cranial morphology it was asserted that Kennewick Man was neither Native American nor closely related to the claimant Plateau tribes of the Pacific Northwest, who claimed ancestral relationship and requested repatriation under the Native American Graves Protection and Repatriation Act (NAGPRA). The morphological analysis was important to judicial decisions that Kennewick Man was not Native American and that therefore NAGPRA did not apply. Instead of repatriation, additional studies of the remains were permitted. Subsequent craniometric analysis affirmed Kennewick Man to be more closely related to circumpacific groups such as the Ainu and Polynesians than he is to modern Native Americans. In order to resolve Kennewick Man's ancestry and affiliations, we have sequenced his genome to approximately 1x coverage and compared it to worldwide genomic data including for the Ainu and Polynesians. We find that Kennewick Man is closer to modern Native Americans than to any other population worldwide. Among the Native American groups for whom genome-wide data are available for comparison, several seem to be descended from a population closely related to that of Kennewick Man, including the Confederated Tribes of the Colville Reservation (Colville), one of the five tribes claiming Kennewick Man. We revisit the cranial analyses and find that, as opposed to genome-wide comparisons, it is not possible on that basis to affiliate Kennewick Man to specific contemporary groups. We therefore conclude based on genetic comparisons that Kennewick Man shows continuity with Native North Americans over at least the last eight millennia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasmussen, Morten -- Sikora, Martin -- Albrechtsen, Anders -- Korneliussen, Thorfinn Sand -- Moreno-Mayar, J Victor -- Poznik, G David -- Zollikofer, Christoph P E -- Ponce de Leon, Marcia S -- Allentoft, Morten E -- Moltke, Ida -- Jonsson, Hakon -- Valdiosera, Cristina -- Malhi, Ripan S -- Orlando, Ludovic -- Bustamante, Carlos D -- Stafford, Thomas W Jr -- Meltzer, David J -- Nielsen, Rasmus -- Willerslev, Eske -- England -- Nature. 2015 Jul 23;523(7561):455-8. doi: 10.1038/nature14625.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Department of Genetics, School of Medicine, Stanford University, Littlefield Center, Stanford, California 94305, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark. ; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. ; Program in Biomedical Informatics, Stanford University, Stanford, California 94305, USA. ; Anthropological Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Department of Archaeology and History, La Trobe University, Melbourne, Victoria 3086, Australia. ; Department of Anthropology and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, 209F Davenport Hall, 607 Matthews Avenue, Urbana, Illinois 61801, USA. ; 1] Department of Genetics, School of Medicine, Stanford University, Littlefield Center, Stanford, California 94305, USA [2] Center for Evolutionary and Human Genomics, Stanford University, Littlefield Center, Stanford, California 94305, USA. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] AMS, 14C Dating Centre, Department of Physics &Astronomy, University of Aarhus, Ny Munkegade 120, DK-8000 Aarhus C, Denmark. ; Department of Anthropology, Southern Methodist University, Dallas, Texas 75275, USA. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark [2] Department of Integrative Biology, University of California, Berkeley, 4134 Valley Life Sciences Building, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26087396" target="_blank"〉PubMed〈/a〉

Description: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617611/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617611/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudmant, Peter H -- Rausch, Tobias -- Gardner, Eugene J -- Handsaker, Robert E -- Abyzov, Alexej -- Huddleston, John -- Zhang, Yan -- Ye, Kai -- Jun, Goo -- Hsi-Yang Fritz, Markus -- Konkel, Miriam K -- Malhotra, Ankit -- Stutz, Adrian M -- Shi, Xinghua -- Paolo Casale, Francesco -- Chen, Jieming -- Hormozdiari, Fereydoun -- Dayama, Gargi -- Chen, Ken -- Malig, Maika -- Chaisson, Mark J P -- Walter, Klaudia -- Meiers, Sascha -- Kashin, Seva -- Garrison, Erik -- Auton, Adam -- Lam, Hugo Y K -- Jasmine Mu, Xinmeng -- Alkan, Can -- Antaki, Danny -- Bae, Taejeong -- Cerveira, Eliza -- Chines, Peter -- Chong, Zechen -- Clarke, Laura -- Dal, Elif -- Ding, Li -- Emery, Sarah -- Fan, Xian -- Gujral, Madhusudan -- Kahveci, Fatma -- Kidd, Jeffrey M -- Kong, Yu -- Lameijer, Eric-Wubbo -- McCarthy, Shane -- Flicek, Paul -- Gibbs, Richard A -- Marth, Gabor -- Mason, Christopher E -- Menelaou, Androniki -- Muzny, Donna M -- Nelson, Bradley J -- Noor, Amina -- Parrish, Nicholas F -- Pendleton, Matthew -- Quitadamo, Andrew -- Raeder, Benjamin -- Schadt, Eric E -- Romanovitch, Mallory -- Schlattl, Andreas -- Sebra, Robert -- Shabalin, Andrey A -- Untergasser, Andreas -- Walker, Jerilyn A -- Wang, Min -- Yu, Fuli -- Zhang, Chengsheng -- Zhang, Jing -- Zheng-Bradley, Xiangqun -- Zhou, Wanding -- Zichner, Thomas -- Sebat, Jonathan -- Batzer, Mark A -- McCarroll, Steven A -- 1000 Genomes Project Consortium -- Mills, Ryan E -- Gerstein, Mark B -- Bashir, Ali -- Stegle, Oliver -- Devine, Scott E -- Lee, Charles -- Eichler, Evan E -- Korbel, Jan O -- P01HG007497/HG/NHGRI NIH HHS/ -- R01 CA166661/CA/NCI NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- R01 HG002898/HG/NHGRI NIH HHS/ -- R01CA166661/CA/NCI NIH HHS/ -- R01GM59290/GM/NIGMS NIH HHS/ -- R01HG002898/HG/NHGRI NIH HHS/ -- R01HG007068/HG/NHGRI NIH HHS/ -- RR029676-01/RR/NCRR NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U41 HG007497/HG/NHGRI NIH HHS/ -- U41HG007497/HG/NHGRI NIH HHS/ -- WT085532/Z/08/Z/Wellcome Trust/United Kingdom -- WT104947/Z/14/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Oct 1;526(7571):75-81. doi: 10.1038/nature15394.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, 3720 15th Avenue NE, Seattle, Washington 98195-5065, USA. ; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Institute for Genome Sciences, University of Maryland School of Medicine, 801 W Baltimore Street, Baltimore, Maryland 21201, USA. ; Department of Genetics, Harvard Medical School, Boston, 25 Shattuck Street, Boston, Massachusetts 02115, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. ; Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA. ; Program in Computational Biology and Bioinformatics, Yale University, BASS 432 &437, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; Department of Molecular Biophysics and Biochemistry, School of Medicine, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA. ; The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Genetics, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA. ; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler St., Houston, Texas 77030, USA. ; Department of Biological Sciences, Louisiana State University, 202 Life Sciences Building, Baton Rouge, Louisiana 70803, USA. ; The Jackson Laboratory for Genomic Medicine, 10 Discovery 263 Farmington Avenue, Farmington, Connecticut 06030, USA. ; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, North Carolina 28223, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520, USA. ; Department of Computational Medicine &Bioinformatics, University of Michigan, 500 S. State Street, Ann Arbor, Michigan 48109, USA. ; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Department of Biology, Boston College, 355 Higgins Hall, 140 Commonwealth Avenue, Chestnut Hill, Massachusetts 02467, USA. ; Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461, USA. ; Bina Technologies, Roche Sequencing, 555 Twin Dolphin Drive, Redwood City, California 94065, USA. ; Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; Department of Computer Engineering, Bilkent University, 06800 Ankara, Turkey. ; University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, California 92093, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 USA. ; Department of Medicine, Washington University in St Louis, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. ; Siteman Cancer Center, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Human Genetics, University of Michigan, 1241 Catherine Street, Ann Arbor, Michigan 48109, USA. ; Molecular Epidemiology, Leiden University Medical Center, Leiden 2300RA, The Netherlands. ; Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. ; The Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, 1305 York Avenue, Weill Cornell Medical College, New York, New York 10065, USA. ; The Feil Family Brain and Mind Research Institute, 413 East 69th St, Weill Cornell Medical College, New York, New York 10065, USA. ; University of Oxford, 1 South Parks Road, Oxford OX3 9DS, UK. ; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. ; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York School of Natural Sciences, 1428 Madison Avenue, New York, New York 10029, USA. ; Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. ; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, 1112 East Clay Street, McGuire Hall, Richmond, Virginia 23298-0581, USA. ; Zentrum fur Molekulare Biologie, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. ; Department of Computer Science, Yale University, 51 Prospect Street, New Haven, Connecticut 06511, USA. ; Department of Graduate Studies - Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, South Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26432246" target="_blank"〉PubMed〈/a〉

Description: DNA methylation is an epigenetic modification associated with transcriptional repression of promoters and is essential for mammalian development. Establishment of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication. Absence of these enzymes is lethal, and somatic mutations in these genes have been associated with several human diseases. How genomic DNA methylation patterns are regulated remains poorly understood, as the mechanisms that guide recruitment and activity of DNMTs in vivo are largely unknown. To gain insights into this matter we determined genomic binding and site-specific activity of the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes localize to methylated, CpG-dense regions in mouse stem cells, yet are excluded from active promoters and enhancers. By specifically measuring sites of de novo methylation, we observe that enzymatic activity reflects binding. De novo methylation increases with CpG density, yet is excluded from nucleosomes. Notably, we observed selective binding of DNMT3B to the bodies of transcribed genes, which leads to their preferential methylation. This targeting to transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baubec, Tuncay -- Colombo, Daniele F -- Wirbelauer, Christiane -- Schmidt, Juliane -- Burger, Lukas -- Krebs, Arnaud R -- Akalin, Altuna -- Schubeler, Dirk -- England -- Nature. 2015 Apr 9;520(7546):243-7. doi: 10.1038/nature14176. Epub 2015 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. ; 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics. Maulbeerstrasse 66, CH-4058 Basel, Switzerland. ; 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Faculty of Sciences, Petersplatz 1, CH-4001 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25607372" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2015 Dec 24;528(7583):459-67. doi: 10.1038/528459a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26701036" target="_blank"〉PubMed〈/a〉

Description: Mutation rates vary within genomes, but the causes of this remain unclear. As many prior inferences rely on methods that assume an absence of selection, potentially leading to artefactual results, we call mutation events directly using a parent-offspring sequencing strategy focusing on Arabidopsis and using rice and honey bee for replication. Here we show that mutation rates are higher in heterozygotes and in proximity to crossover events. A correlation between recombination rate and intraspecific diversity is in part owing to a higher mutation rate in domains of high recombination/diversity. Implicating diversity per se as a cause, we find an approximately 3.5-fold higher mutation rate in heterozygotes than in homozygotes, with mutations occurring in closer proximity to heterozygous sites than expected by chance. In a genome that is a patchwork of heterozygous and homozygous domains, mutations occur disproportionately more often in the heterozygous domains. If segregating mutations predispose to a higher local mutation rate, clusters of genes dominantly under purifying selection (more commonly homozygous) and under balancing selection (more commonly heterozygous), might have low and high mutation rates, respectively. Our results are consistent with this, there being a ten times higher mutation rate in pathogen resistance genes, expected to be under positive or balancing selection. Consequently, we do not necessarily need to evoke extremely weak selection on the mutation rate to explain why mutational hot and cold spots might correspond to regions under positive/balancing and purifying selection, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Sihai -- Wang, Long -- Huang, Ju -- Zhang, Xiaohui -- Yuan, Yang -- Chen, Jian-Qun -- Hurst, Laurence D -- Tian, Dacheng -- England -- Nature. 2015 Jul 23;523(7561):463-7. doi: 10.1038/nature14649. Epub 2015 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China. ; The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26176923" target="_blank"〉PubMed〈/a〉

Description: The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773891/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉UK10K Consortium -- Walter, Klaudia -- Min, Josine L -- Huang, Jie -- Crooks, Lucy -- Memari, Yasin -- McCarthy, Shane -- Perry, John R B -- Xu, ChangJiang -- Futema, Marta -- Lawson, Daniel -- Iotchkova, Valentina -- Schiffels, Stephan -- Hendricks, Audrey E -- Danecek, Petr -- Li, Rui -- Floyd, James -- Wain, Louise V -- Barroso, Ines -- Humphries, Steve E -- Hurles, Matthew E -- Zeggini, Eleftheria -- Barrett, Jeffrey C -- Plagnol, Vincent -- Richards, J Brent -- Greenwood, Celia M T -- Timpson, Nicholas J -- Durbin, Richard -- Soranzo, Nicole -- 091551/Wellcome Trust/United Kingdom -- 095515/Wellcome Trust/United Kingdom -- 095564/Wellcome Trust/United Kingdom -- 098498/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- 104036/Wellcome Trust/United Kingdom -- CZD/16/6/4/Chief Scientist Office/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- RG/10/13/28570/British Heart Foundation/United Kingdom -- WT091310/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Oct 1;526(7571):82-90. doi: 10.1038/nature14962. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367797" target="_blank"〉PubMed〈/a〉

Description: Although reconstruction of the phylogeny of living birds has progressed tremendously in the last decade, the evolutionary history of Neoaves--a clade that encompasses nearly all living bird species--remains the greatest unresolved challenge in dinosaur systematics. Here we investigate avian phylogeny with an unprecedented scale of data: 〉390,000 bases of genomic sequence data from each of 198 species of living birds, representing all major avian lineages, and two crocodilian outgroups. Sequence data were collected using anchored hybrid enrichment, yielding 259 nuclear loci with an average length of 1,523 bases for a total data set of over 7.8 x 10(7) bases. Bayesian and maximum likelihood analyses yielded highly supported and nearly identical phylogenetic trees for all major avian lineages. Five major clades form successive sister groups to the rest of Neoaves: (1) a clade including nightjars, other caprimulgiforms, swifts, and hummingbirds; (2) a clade uniting cuckoos, bustards, and turacos with pigeons, mesites, and sandgrouse; (3) cranes and their relatives; (4) a comprehensive waterbird clade, including all diving, wading, and shorebirds; and (5) a comprehensive landbird clade with the enigmatic hoatzin (Opisthocomus hoazin) as the sister group to the rest. Neither of the two main, recently proposed Neoavian clades--Columbea and Passerea--were supported as monophyletic. The results of our divergence time analyses are congruent with the palaeontological record, supporting a major radiation of crown birds in the wake of the Cretaceous-Palaeogene (K-Pg) mass extinction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prum, Richard O -- Berv, Jacob S -- Dornburg, Alex -- Field, Daniel J -- Townsend, Jeffrey P -- Lemmon, Emily Moriarty -- Lemmon, Alan R -- England -- Nature. 2015 Oct 22;526(7574):569-73. doi: 10.1038/nature15697. Epub 2015 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology &Evolutionary Biology, Yale University, New Haven, Connecticut 06520, USA. ; Peabody Museum of Natural History, Yale University, New Haven, Connecticut 06520, USA. ; Department of Ecology and Evolutionary Biology, Fuller Evolutionary Biology Program, Cornell University, and Cornell Laboratory of Ornithology, Ithaca, New York 14853, USA. ; North Carolina Museum of Natural Sciences, Raleigh, North Carolina 27601, USA. ; Department of Geology &Geophysics, Yale University, New Haven, Connecticut 06520, USA. ; Department of Biostatistics, and Program in Computational Biology and Bioinformatics, Yale University, NewHaven, Connecticut 06520, USA. ; Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA. ; Department of Scientific Computing, Florida State University, Tallahassee, Florida 32306, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26444237" target="_blank"〉PubMed〈/a〉

Description: Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to 〉/=4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puente, Xose S -- Bea, Silvia -- Valdes-Mas, Rafael -- Villamor, Neus -- Gutierrez-Abril, Jesus -- Martin-Subero, Jose I -- Munar, Marta -- Rubio-Perez, Carlota -- Jares, Pedro -- Aymerich, Marta -- Baumann, Tycho -- Beekman, Renee -- Belver, Laura -- Carrio, Anna -- Castellano, Giancarlo -- Clot, Guillem -- Colado, Enrique -- Colomer, Dolors -- Costa, Dolors -- Delgado, Julio -- Enjuanes, Anna -- Estivill, Xavier -- Ferrando, Adolfo A -- Gelpi, Josep L -- Gonzalez, Blanca -- Gonzalez, Santiago -- Gonzalez, Marcos -- Gut, Marta -- Hernandez-Rivas, Jesus M -- Lopez-Guerra, Monica -- Martin-Garcia, David -- Navarro, Alba -- Nicolas, Pilar -- Orozco, Modesto -- Payer, Angel R -- Pinyol, Magda -- Pisano, David G -- Puente, Diana A -- Queiros, Ana C -- Quesada, Victor -- Romeo-Casabona, Carlos M -- Royo, Cristina -- Royo, Romina -- Rozman, Maria -- Russinol, Nuria -- Salaverria, Itziar -- Stamatopoulos, Kostas -- Stunnenberg, Hendrik G -- Tamborero, David -- Terol, Maria J -- Valencia, Alfonso -- Lopez-Bigas, Nuria -- Torrents, David -- Gut, Ivo -- Lopez-Guillermo, Armando -- Lopez-Otin, Carlos -- Campo, Elias -- England -- Nature. 2015 Oct 22;526(7574):519-24. doi: 10.1038/nature14666. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain. ; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. ; Unitat de Hematologia, Hospital Clinic, IDIBAPS, Universitat de Barcelona, 08036 Barcelona, Spain. ; Departament d'Anatomia Patologica, Microbiologia i Farmacologia, Universitat de Barcelona, 08036 Barcelona, Spain. ; Programa Conjunto de Biologia Computacional, Barcelona Supercomputing Center (BSC), Institut de Recerca Biomedica (IRB), Spanish National Bioinformatics Institute, Universitat de Barcelona, 08028 Barcelona, Spain. ; Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain. ; Unidad de Genomica, IDIBAPS, 08036 Barcelona, Spain. ; Servicio de Hematologia, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain. ; Institute for Cancer Genetics, Columbia University, New York 10032, USA. ; Servicio de Hematologia, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. ; Center for Genomic Regulation (CRG), Pompeu Fabra University (UPF), Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain. ; Servicio de Hematologia, IBSAL-Hospital Universitario de Salamanca, Centro de Investigacion del Cancer, Universidad de Salamanca-CSIC, 37007 Salamanca, Spain. ; Centro Nacional de Analisis Genomico, Parc Cientific de Barcelona, 08028 Barcelona, Spain. ; Catedra Inter-Universitaria de Derecho y Genoma Humano, Universidad de Deusto, Universidad del Pais Vasco, 48007 Bilbao, Spain. ; Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Spanish National Bioinformatics Institute, 28029 Madrid, Spain. ; Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thermi, Thessaloniki, Greece. ; Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands. ; Servicio de Hematologia, Hospital Clinico de Valencia, 46010 Valencia, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200345" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merali, Zeeya -- England -- Nature. 2015 Nov 12;527(7577):145. doi: 10.1038/nature.2015.18746.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560277" target="_blank"〉PubMed〈/a〉

Description: Stem cells self-renew and generate specialized progeny through differentiation, but vary in the range of cells and tissues they generate, a property called developmental potency. Pluripotent stem cells produce all cells of an organism, while multipotent or unipotent stem cells regenerate only specific lineages or tissues. Defining stem-cell potency relies upon functional assays and diagnostic transcriptional, epigenetic and metabolic states. Here we describe functional and molecular hallmarks of pluripotent stem cells, propose a checklist for their evaluation, and illustrate how forensic genomics can validate their provenance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Los Angeles, Alejandro -- Ferrari, Francesco -- Xi, Ruibin -- Fujiwara, Yuko -- Benvenisty, Nissim -- Deng, Hongkui -- Hochedlinger, Konrad -- Jaenisch, Rudolf -- Lee, Soohyun -- Leitch, Harry G -- Lensch, M William -- Lujan, Ernesto -- Pei, Duanqing -- Rossant, Janet -- Wernig, Marius -- Park, Peter J -- Daley, George Q -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 24;525(7570):469-78. doi: 10.1038/nature15515.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children's Hospital Boston, and Dana-Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA. ; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; School of Mathematical Sciences and Center for Statistical Science, Peking University, Beijing 100871, China. ; Stem Cell Unit, Department of Genetics, Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. ; College of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts 02114, USA. ; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA. ; South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. ; The Hospital for Sick Children Research Institute, Toronto, Ontario ON M5G 0A4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26399828" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsnelson, Alla -- England -- Nature. 2015 Oct 8;526(7572):S4-5. doi: 10.1038/526S4a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26444373" target="_blank"〉PubMed〈/a〉

Description: Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/ .

Description: Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required.

Description: Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff , (M1) and Hivep1, Nfil3, Prdm1 , (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.

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 Climate 27 (2014): 2405–2416, doi:10.1175/JCLI-D-13-00359.1.

Description: Several recent studies utilizing global climate models predict that the Pacific Equatorial Undercurrent (EUC) will strengthen over the twenty-first century. Here, historical changes in the tropical Pacific are investigated using the Simple Ocean Data Assimilation (SODA) reanalysis toward understanding the dynamics and mechanisms that may dictate such a change. Although SODA does not assimilate velocity observations, the seasonal-to-interannual variability of the EUC estimated by SODA corresponds well with moored observations over a ~20-yr common period. Long-term trends in SODA indicate that the EUC core velocity has increased by 16% century−1 and as much as 47% century−1 at fixed locations since the mid-1800s. Diagnosis of the zonal momentum budget in the equatorial Pacific reveals two distinct seasonal mechanisms that explain the EUC strengthening. The first is characterized by strengthening of the western Pacific trade winds and hence oceanic zonal pressure gradient during boreal spring. The second entails weakening of eastern Pacific trade winds during boreal summer, which weakens the surface current and reduces EUC deceleration through vertical friction. EUC strengthening has important ecological implications as upwelling affects the thermal and biogeochemical environment. Furthermore, given the potential large-scale influence of EUC strength and depth on the heat budget in the eastern Pacific, the seasonal strengthening of the EUC may help reconcile paradoxical observations of Walker circulation slowdown and zonal SST gradient strengthening. Such a process would represent a new dynamical “thermostat” on CO2-forced warming of the tropical Pacific Ocean, emphasizing the importance of ocean dynamics and seasonality in understanding climate change projections.

Description: EJDis supported by NSFGrantsOCE-1031971 and OCE-1233282. KBK is supported by NSF Grant OCE-1233282.

Description: 2014-09-15

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 Atmospheric and Oceanic Technology 21 (2014): 2015–2025, doi:10.1175/JTECH-D-13-00262.1.

Description: The NOAA Tropical Atmosphere Ocean (TAO) moored array has, for three decades, been a valuable resource for monitoring and forecasting El Niño–Southern Oscillation and understanding physical oceanographic as well as coupled processes in the tropical Pacific influencing global climate. Acoustic Doppler current profiler (ADCP) measurements by TAO moorings provide benchmarks for evaluating numerical simulations of subsurface circulation including the Equatorial Undercurrent (EUC). Meanwhile, the Sea Education Association (SEA) has been collecting data during repeat cruises to the central equatorial Pacific Ocean (160°–126°W) throughout the past decade that provide useful cross validation and quantitative insight into the potential for stationary observing platforms such as TAO to incur sampling biases related to the strength of the EUC. This paper describes some essential sampling characteristics of the SEA dataset, compares SEA and TAO velocity measurements in the vicinity of the EUC, shares new insight into EUC characteristics and behavior only observable in repeat cross-equatorial sections, and estimates the sampling bias incurred by equatorial TAO moorings in their estimates of the velocity and transport of the EUC. The SEA high-resolution ADCP dataset compares well with concurrent TAO measurements (RMSE = 0.05 m s−1; R2 = 0.98), suggests that the EUC core meanders sinusoidally about the equator between ±0.4° latitude, and reveals a mean sampling bias of equatorial measurements (e.g., TAO) of the EUC’s zonal velocity of −0.14 ± 0.03 m s−1 as well as a ~10% underestimation of EUC volume transport. A bias-corrected monthly record and climatology of EUC strength at 140°W for 1990–2010 is presented.

Description: The authors thank the NSF Physical Oceanography program (OCE-1233282) and the WHOI Academic Programs Office for funding.

Description: 2015-03-01

Description: Author Posting. © American Meteorological Society, 2013. 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 43 (2013): 1398–1406, doi:10.1175/JPO-D-13-028.1.

Description: An adiabatic, inertial, and quasigeostrophic model is used to discuss the interaction of surface Ekman transport with an island. The theory extends the recent work of Spall and Pedlosky to include an analytical and nonlinear model for the interaction. The presence of an island that interrupts a uniform Ekman layer transport raises interesting questions about the resulting circulation. The consequential upwelling around the island can lead to a local intake of fluid from the geostrophic region beneath the Ekman layer or to a more complex flow around the island in which the fluid entering the Ekman layer on one portion of the island's perimeter is replaced by a flow along the island's boundary from a downwelling region located elsewhere on the island. This becomes especially pertinent when the flow is quasigeostrophic and adiabatic. The oncoming geostrophic flow that balances the offshore Ekman flux is largely diverted around the island, and the Ekman flux is fed by a transfer of fluid from the western to the eastern side of the island. As opposed to the linear, dissipative model described earlier, this transfer takes place even in the absence of a topographic skirt around the island. The principal effect of topography in the inertial model is to introduce an asymmetry between the circulation on the northern and southern sides of the island. The quasigeostrophic model allows a simple solution to the model problem with topography and yet the resulting three-dimensional circulation is surprisingly complex with streamlines connecting each side of the island.

Description: This research was supported in part by NSF Grant OCE Grant 0925061.

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 Climate 27 (2014): 2842–2860, doi:10.1175/JCLI-D-13-00227.1.

Description: Mooring measurements from the Kuroshio Extension System Study (June 2004–June 2006) and from the ongoing Kuroshio Extension Observatory (June 2004–present) are combined with float measurements of the Argo network to study the variability of the North Pacific Subtropical Mode Water (STMW) across the entire gyre, on time scales from days, to seasons, to a decade. The top of the STMW follows a seasonal cycle, although observations reveal that it primarily varies in discrete steps associated with episodic wind events. The variations of the STMW bottom depth are tightly related to the sea surface height (SSH), reflecting mesoscale eddies and large-scale variations of the Kuroshio Extension and recirculation gyre systems. Using the observed relationship between SSH and STMW, gridded SSH products and in situ estimates from floats are used to construct weekly maps of STMW thickness, providing nonbiased estimates of STMW total volume, annual formation and erosion volumes, and seasonal and interannual variability for the past decade. Year-to-year variations are detected, particularly a significant decrease of STMW volume in 2007–10 primarily attributable to a smaller volume formed. Variability of the heat content in the mode water region is dominated by the seasonal cycle and mesoscale eddies; there is only a weak link to STMW on interannual time scales, and no long-term trends in heat content and STMW thickness between 2002 and 2011 are detected. Weak lagged correlations among air–sea fluxes, oceanic heat content, and STMW thickness are found when averaged over the northwestern Pacific recirculation gyre region.

Description: This work was sponsored by the National Science Foundation (Grants OCE-0220161, OCE-0825152, and OCE-0827125).

Description: 2014-10-15

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): 149–163, doi:10.1175/JPO-D-13-0136.1.

Description: Monthly mapped sea level anomalies (MSLAs) of the NW Atlantic in the region immediately downstream of the Gulf Stream (GS) separation point reveal a leading mode in which the path shifts approximately 100 km meridionally about a nominal latitude of 39°N, producing coherent sea level anomaly (SLA) variability from 72° to 50°W. This mode can be captured by use of a simple 16-point index based on SLA data taken along the maximum of the observed variability in the region 33°–46°N and 45°–75°W. The GS shifts between 2010 and 2012 are the largest of the last decade and equal to the largest of the entire record. The second group of EOF modes of variability describes GS meanders, which propagate mainly westward interrupted by brief periods of eastward or stationary meanders. These meanders have wavelengths of approximately 400 km and can be seen in standard EOFs by spatial phase shifting of a standing meander pattern in the SLA data. The spectral properties of these modes indicate strong variability at interannual and longer periods for the first mode and periods of a few to several months for the meanders. While the former is quite similar to a previous use of the altimeter for GS path, the simple index is a useful measure of the large-scale shifts in the GS path that is quickly estimated and updated without changes in previous estimates. The time-scale separation allows a low-pass filtered 16-point index to be reflective of large-scale, coherent shifts in the GS path.

Description: Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) grant program of Apoyo al Personal Investigador en Formación and NSF Grant OCE-0726720

Description: 2014-07-01

Description: The advent in high-throughput-sequencing (HTS) technologies has revolutionized conventional biodiversity research by enabling parallel capture of DNA sequences possessing species-level diagnosis. However, polymerase chain reaction (PCR)-based implementation is biased by the efficiency of primer binding across lineages of organisms. A PCR-free HTS approach will alleviate this artefact and significantly improve upon the multi-locus method utilizing full mitogenomes. Here we developed a novel multiplex sequencing and assembly pipeline allowing for simultaneous acquisition of full mitogenomes from pooled animals without DNA enrichment or amplification. By concatenating assemblies from three de novo assemblers, we obtained high-quality mitogenomes for all 49 pooled taxa, with 36 species 〉15 kb and the remaining 〉10 kb, including 20 complete mitogenomes and nearly all protein coding genes (99.6%). The assembly quality was carefully validated with Sanger sequences, reference genomes and conservativeness of protein coding genes across taxa. The new method was effective even for closely related taxa, e.g. three Drosophila spp., demonstrating its broad utility for biodiversity research and mito-phylogenomics. Finally, the in silico simulation showed that by recruiting multiple mito-loci, taxon detection was improved at a fixed sequencing depth. Combined, these results demonstrate the plausibility of a multi-locus mito-metagenomics approach as the next phase of the current single-locus metabarcoding method.

Description: Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes or are studied in vitro . Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.

Description: A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline ( http://canbind.princeton.edu ) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteins—specifically those known to be involved in molecular interactions—our approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer.

Description: Genome duplication with hybridization, or allopolyploidization, occurs commonly in plants, and is considered to be a strong force for generating new species. However, genome-wide quantification of homeolog expression ratios was technically hindered because of the high homology between homeologous gene pairs. To quantify the homeolog expression ratio using RNA-seq obtained from polyploids, a new method named HomeoRoq was developed, in which the genomic origin of sequencing reads was estimated using mismatches between the read and each parental genome. To verify this method, we first assembled the two diploid parental genomes of Arabidopsis halleri subsp. gemmifera and Arabidopsis lyrata subsp. petraea ( Arabidopsis petraea subsp. umbrosa ), then generated a synthetic allotetraploid, mimicking the natural allopolyploid Arabidopsis kamchatica . The quantified ratios corresponded well to those obtained by Pyrosequencing. We found that the ratios of homeologs before and after cold stress treatment were highly correlated ( r = 0.870). This highlights the presence of nonstochastic polyploid gene regulation despite previous research identifying stochastic variation in expression. Moreover, our new statistical test incorporating overdispersion identified 226 homeologs (1.11% of 20 369 expressed homeologs) with significant ratio changes, many of which were related to stress responses. HomeoRoq would contribute to the study of the genes responsible for polyploid-specific environmental responses.

Description: Reconstructing the evolutionary relationships of species is a major goal in biology. Despite the increasing number of completely sequenced genomes, a large number of phylogenetic projects rely on targeted sequencing and analysis of a relatively small sample of marker genes. The selection of these phylogenetic markers should ideally be based on accurate predictions of their combined, rather than individual, potential to accurately resolve the phylogeny of interest. Here we present and validate a new phylogenomics strategy to efficiently select a minimal set of stable markers able to reconstruct the underlying species phylogeny. In contrast to previous approaches, our methodology does not only rely on the ability of individual genes to reconstruct a known phylogeny, but it also explores the combined power of sets of concatenated genes to accurately infer phylogenetic relationships of species not previously analyzed. We applied our approach to two broad sets of cyanobacterial and ascomycetous fungal species, and provide two minimal sets of six and four genes, respectively, necessary to fully resolve the target phylogenies. This approach paves the way for the informed selection of phylogenetic markers in the effort of reconstructing the tree of life.

Description: Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550673/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550673/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bos, Kirsten I -- Harkins, Kelly M -- Herbig, Alexander -- Coscolla, Mireia -- Weber, Nico -- Comas, Inaki -- Forrest, Stephen A -- Bryant, Josephine M -- Harris, Simon R -- Schuenemann, Verena J -- Campbell, Tessa J -- Majander, Kerttu -- Wilbur, Alicia K -- Guichon, Ricardo A -- Wolfe Steadman, Dawnie L -- Cook, Della Collins -- Niemann, Stefan -- Behr, Marcel A -- Zumarraga, Martin -- Bastida, Ricardo -- Huson, Daniel -- Nieselt, Kay -- Young, Douglas -- Parkhill, Julian -- Buikstra, Jane E -- Gagneux, Sebastien -- Stone, Anne C -- Krause, Johannes -- 098051/Wellcome Trust/United Kingdom -- AI090928/AI/NIAID NIH HHS/ -- MC_U117581288/Medical Research Council/United Kingdom -- R01 AI090928/AI/NIAID NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Oct 23;514(7523):494-7. doi: 10.1038/nature13591. Epub 2014 Aug 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Archaeological Sciences, University of Tubingen, Ruemelinstrasse 23, 72070 Tubingen, Germany [2]. ; 1] School of Human Evolution and Social Change, Arizona State University, PO Box 872402, Tempe, Arizona 85287-2402, USA [2]. ; 1] Department of Archaeological Sciences, University of Tubingen, Ruemelinstrasse 23, 72070 Tubingen, Germany [2] Center for Bioinformatics, University of Tubingen, Sand 14, 72076 Tubingen, Germany [3]. ; 1] Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland [2] University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland [3]. ; Center for Bioinformatics, University of Tubingen, Sand 14, 72076 Tubingen, Germany. ; 1] Genomics and Health Unit, FISABIO-Public Health, Avenida Cataluna 21, 46020 Valencia, Spain [2] CIBER (Centros de Investigacion Biomedica en Red) in Epidemiology and Public Health, Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5, Pabellon 11, Planta 0, 28029 Madrid, Spain. ; Department of Archaeological Sciences, University of Tubingen, Ruemelinstrasse 23, 72070 Tubingen, Germany. ; Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. ; Department of Archaeology, University of Cape Town, Private Bag X1, Rondebosch, 7701, South Africa. ; School of Human Evolution and Social Change, Arizona State University, PO Box 872402, Tempe, Arizona 85287-2402, USA. ; CONICET, Laboratorio de Ecologia Evolutiva Humana (FACSO, UNCPBA), Departamento de Biologia (FCEyN, UNMDP), Calle 508 No. 881 (7631), Quequen, Argentina. ; Department of Anthropology, University of Tennessee, 250 South Stadium Hall, Knoxville, Tennessee 37996, USA. ; Department of Anthropology, Indiana University, 701 East Kirkwood Avenue, Bloomington, Indiana 47405-7100, USA. ; 1] Molecular Mycobacteriology, Forschungszentrum Borstel, Parkallee 1, 23845 Borstel, Germany [2] German Center for Infection Research, Forschungszentrum Borstel, Parkallee 1, 23845 Borstel, Germany. ; McGill International TB Centre, McGill University, 1650 Cedar Avenue, Montreal H3G 1A4, Canada. ; Biotechnology Institute, CICVyA-INTA Castelar, Dr. Nicolas Repetto y De Los Reseros S/N, (B1686IGC) Hurlingham, Buenos Aires, Argentina. ; Instituto de Investigaciones Marinas y Costeras (CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, San Luis 1722, Mar del Plata 7600, Argentina. ; 1] Department of Medicine, Imperial College, London W2 1PG, UK [2] Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. ; 1] Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland [2] University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland. ; 1] Department of Archaeological Sciences, University of Tubingen, Ruemelinstrasse 23, 72070 Tubingen, Germany [2] Senckenberg Centre for Human Evolution and Palaeoenvironment, University of Tubingen, Tubingen 72070, Germany [3] Max Planck Institute for Science and History, Khalaische Strasse 10, 07745 Jena, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25141181" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wright, Jessica -- England -- Nature. 2014 Apr 3;508(7494):S6-7. doi: 10.1038/508S6a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695335" target="_blank"〉PubMed〈/a〉

Description: Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530805/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Araya, Carlos L -- Kawli, Trupti -- Kundaje, Anshul -- Jiang, Lixia -- Wu, Beijing -- Vafeados, Dionne -- Terrell, Robert -- Weissdepp, Peter -- Gevirtzman, Louis -- Mace, Daniel -- Niu, Wei -- Boyle, Alan P -- Xie, Dan -- Ma, Lijia -- Murray, John I -- Reinke, Valerie -- Waterston, Robert H -- Snyder, Michael -- R01 GM072675/GM/NIGMS NIH HHS/ -- U01 HG004267/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Aug 28;512(7515):400-5. doi: 10.1038/nature13497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA. ; Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164749" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Dec 18;516(7531):S75. doi: 10.1038/516S75a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517246" target="_blank"〉PubMed〈/a〉

Description: Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Brana-Arintero site in Leon, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Brana individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269527/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269527/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olalde, Inigo -- Allentoft, Morten E -- Sanchez-Quinto, Federico -- Santpere, Gabriel -- Chiang, Charleston W K -- DeGiorgio, Michael -- Prado-Martinez, Javier -- Rodriguez, Juan Antonio -- Rasmussen, Simon -- Quilez, Javier -- Ramirez, Oscar -- Marigorta, Urko M -- Fernandez-Callejo, Marcos -- Prada, Maria Encina -- Encinas, Julio Manuel Vidal -- Nielsen, Rasmus -- Netea, Mihai G -- Novembre, John -- Sturm, Richard A -- Sabeti, Pardis -- Marques-Bonet, Tomas -- Navarro, Arcadi -- Willerslev, Eske -- Lalueza-Fox, Carles -- F32 GM106656/GM/NIGMS NIH HHS/ -- F32GM106656/GM/NIGMS NIH HHS/ -- R01 HG007089/HG/NHGRI NIH HHS/ -- R01-HG007089/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Mar 13;507(7491):225-8. doi: 10.1038/nature12960. Epub 2014 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2]. ; 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark [2]. ; Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA. ; 1] Department of Integrative Biology, University of California, Berkeley, California 94720, USA [2] Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, Pennsylvania 16802, USA. ; Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark. ; I.E.S.O. 'Los Salados', Junta de Castilla y Leon, E-49600 Benavente, Spain. ; Junta de Castilla y Leon, Servicio de Cultura de Leon, E-24071 Leon, Spain. ; Center for Theoretical Evolutionary Genomics, University of California, Berkeley, California 94720, USA. ; Department of Medicine and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, 6500 Nijmegen, The Netherlands. ; Department of Human Genetics, University of Chicago, Illinois 60637, USA. ; Institute for Molecular Bioscience, Melanogenix Group, The University of Queensland, Brisbane, Queensland 4072, Australia. ; 1] Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain. ; 1] Institut de Biologia Evolutiva, CSIC-UPF, Barcelona 08003, Spain [2] Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Catalonia, Spain [3] Centre de Regulacio Genomica (CRG), Barcelona 08003, Catalonia, Spain [4] National Institute for Bioinformatics (INB), Barcelona 08003, Catalonia, Spain. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463515" target="_blank"〉PubMed〈/a〉

Description: Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353498/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brawand, David -- Wagner, Catherine E -- Li, Yang I -- Malinsky, Milan -- Keller, Irene -- Fan, Shaohua -- Simakov, Oleg -- Ng, Alvin Y -- Lim, Zhi Wei -- Bezault, Etienne -- Turner-Maier, Jason -- Johnson, Jeremy -- Alcazar, Rosa -- Noh, Hyun Ji -- Russell, Pamela -- Aken, Bronwen -- Alfoldi, Jessica -- Amemiya, Chris -- Azzouzi, Naoual -- Baroiller, Jean-Francois -- Barloy-Hubler, Frederique -- Berlin, Aaron -- Bloomquist, Ryan -- Carleton, Karen L -- Conte, Matthew A -- D'Cotta, Helena -- Eshel, Orly -- Gaffney, Leslie -- Galibert, Francis -- Gante, Hugo F -- Gnerre, Sante -- Greuter, Lucie -- Guyon, Richard -- Haddad, Natalie S -- Haerty, Wilfried -- Harris, Rayna M -- Hofmann, Hans A -- Hourlier, Thibaut -- Hulata, Gideon -- Jaffe, David B -- Lara, Marcia -- Lee, Alison P -- MacCallum, Iain -- Mwaiko, Salome -- Nikaido, Masato -- Nishihara, Hidenori -- Ozouf-Costaz, Catherine -- Penman, David J -- Przybylski, Dariusz -- Rakotomanga, Michaelle -- Renn, Suzy C P -- Ribeiro, Filipe J -- Ron, Micha -- Salzburger, Walter -- Sanchez-Pulido, Luis -- Santos, M Emilia -- Searle, Steve -- Sharpe, Ted -- Swofford, Ross -- Tan, Frederick J -- Williams, Louise -- Young, Sarah -- Yin, Shuangye -- Okada, Norihiro -- Kocher, Thomas D -- Miska, Eric A -- Lander, Eric S -- Venkatesh, Byrappa -- Fernald, Russell D -- Meyer, Axel -- Ponting, Chris P -- Streelman, J Todd -- Lindblad-Toh, Kerstin -- Seehausen, Ole -- Di Palma, Federica -- 2R01DE019637-04/DE/NIDCR NIH HHS/ -- F30 DE023013/DE/NIDCR NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- R01 DE019637/DE/NIDCR NIH HHS/ -- R01 NS034950/NS/NINDS NIH HHS/ -- U54 HG002045/HG/NHGRI NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Sep 18;513(7518):375-81. doi: 10.1038/nature13726. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] MRC Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, UK [3]. ; 1] Department of Fish Ecology and Evolution, Eawag Swiss Federal Institute of Aquatic Science and Technology, Center for Ecology, Evolution &Biogeochemistry, CH-6047 Kastanienbaum, Switzerland [2] Division of Aquatic Ecology, Institute of Ecology &Evolution, University of Bern, CH-3012 Bern, Switzerland [3]. ; 1] MRC Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, UK [2]. ; 1] Gurdon Institute, Cambridge CB2 1QN, UK [2] Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; Division of Aquatic Ecology, Institute of Ecology &Evolution, University of Bern, CH-3012 Bern, Switzerland. ; Department of Biology, University of Konstanz, D-78457 Konstanz, Germany. ; 1] Department of Biology, University of Konstanz, D-78457 Konstanz, Germany [2] European Molecular Biology Laboratory, 69117 Heidelberg, Germany. ; Institute of Molecular and Cell Biology, A*STAR, 138673 Singapore. ; Department of Biology, Reed College, Portland, Oregon 97202, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Biology Department, Stanford University, Stanford, California 94305-5020, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA. ; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA. ; Institut Genetique et Developpement, CNRS/University of Rennes, 35043 Rennes, France. ; CIRAD, Campus International de Baillarguet, TA B-110/A, 34398 Montpellier cedex 5, France. ; School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332-0230, USA. ; Department of Biology, University of Maryland, College Park, Maryland 20742, USA. ; Animal Genetics, Institute of Animal Science, ARO, The Volcani Center, Bet-Dagan, 50250 Israel. ; Zoological Institute, University of Basel, CH-4051 Basel, Switzerland. ; 1] Department of Fish Ecology and Evolution, Eawag Swiss Federal Institute of Aquatic Science and Technology, Center for Ecology, Evolution &Biogeochemistry, CH-6047 Kastanienbaum, Switzerland [2] Division of Aquatic Ecology, Institute of Ecology &Evolution, University of Bern, CH-3012 Bern, Switzerland. ; MRC Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, UK. ; Department of Integrative Biology, Center for Computational Biology and Bioinformatics; The University of Texas at Austin, Austin, Texas 78712, USA. ; Department of Fish Ecology and Evolution, Eawag Swiss Federal Institute of Aquatic Science and Technology, Center for Ecology, Evolution &Biogeochemistry, CH-6047 Kastanienbaum, Switzerland. ; Department of Biological Sciences, Tokyo Institute of Technology, Tokyo, 226-8501 Yokohama, Japan. ; Systematique, Adaptation, Evolution, National Museum of Natural History, 75005 Paris, France. ; Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, UK. ; Carnegie Institution of Washington, Department of Embryology, 3520 San Martin Drive Baltimore, Maryland 21218, USA. ; 1] Department of Biological Sciences, Tokyo Institute of Technology, Tokyo, 226-8501 Yokohama, Japan [2] National Cheng Kung University, Tainan City, 704 Taiwan. ; Gurdon Institute, Cambridge CB2 1QN, UK. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Vertebrate and Health Genomics, The Genome Analysis Centre, Norwich NR18 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186727" target="_blank"〉PubMed〈/a〉

Description: Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Necsulea, Anamaria -- Soumillon, Magali -- Warnefors, Maria -- Liechti, Angelica -- Daish, Tasman -- Zeller, Ulrich -- Baker, Julie C -- Grutzner, Frank -- Kaessmann, Henrik -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Jan 30;505(7485):635-40. doi: 10.1038/nature12943. Epub 2014 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland [2] Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland [3] Laboratory of Developmental Genomics, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland (A.N.); Harvard Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA, and Broad Institute, Cambridge, Massachusetts 02142, USA (M.S.). ; 1] Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland [2] Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. ; The Robinson Institute, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia. ; Department of Systematic Zoology, Faculty of Agriculture and Horticulture, Humboldt University Berlin, 10099 Berlin, Germany. ; Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463510" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 Oct 30;514(7524):548. doi: 10.1038/514548a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355341" target="_blank"〉PubMed〈/a〉