DeFCoM: analysis and modeling of transcription factor binding sites using a motif-centric genomic footprinter

Identifying the locations of transcription factor binding sites is critical for understanding how gene transcription is regulated across different cell types and conditions. Chromatin accessibility experiments such as DNaseI sequencing (DNase-seq) and Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) produce genome-wide data that include distinct "footprint" patterns at binding sites. Nearly all existing computational methods to detect footprints from these data assume that footprint signals are highly homogeneous across footprint sites. Additionally, a comprehensive and systematic comparison of footprinting methods for specifically identifying which motif sites for a specific factor are bound has not been performed. Using DNase-seq data from the ENCODE project, we show that a large degree of previously uncharacterized site-to-site variability exists in footprint signal across motif sites for a transcription factor. To model this heterogeneity in the data, we introduce a novel, supervised learning footprinter called DeFCoM (Detecting Footprints Containing Motifs). We compare DeFCoM to nine existing methods using evaluation sets from four human cell-lines and eighteen transcription factors and show that DeFCoM outperforms current methods in determining bound and unbound motif sites. We also analyze the impact of several biological and technical factors on the quality of footprint predictions to highlight important considerations when conducting footprint analyses and assessing the performance of footprint prediction methods. Lastly, we show that DeFCoM can detect footprints using ATAC-seq data with similar accuracy as when using DNase-seq data. Python code available at https://bitbucket.org/bryancquach/defcom CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary information available at Bioinformatics online

Iceland-Scotland Overflow Water transport variability through the Charlie-Gibbs Fracture Zone and the impact of the North Atlantic Current

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 6989–7012, doi:10.1002/2017JC012698.The Charlie-Gibbs Fracture Zone (CGFZ), a deep and wide gap in the Mid-Atlantic Ridge near 52°N, is a gateway between the eastern and western subpolar regions for the Atlantic Meridional Overturning Circulation (AMOC). In 2010–2012, an eight-mooring array of current meters and temperature/salinity sensors was installed across the CGFZ between 500 m and the sea floor to measure the mean transport of westward-flowing Iceland-Scotland Overflow Water (ISOW) and investigate the impact of the eastward-flowing North Atlantic Current (NAC) on ISOW transport variability. The 22 month record mean ISOW transport through the CGFZ, −1.7 ± 0.5 Sv (95% confidence interval), is 30% lower than the previously published estimate based on 13 months of current-only measurements, −2.4 ± 1.2 Sv. The latter mean estimate may have been biased high due to the lack of continuous salinity measurements, although the two estimates are not statistically different due to strong mesoscale variability in both data sets. Empirical Orthogonal Function analysis and maps of satellite-derived absolute dynamic topography show that weak westward ISOW transport events and eastward reversals are caused by northward meanders of the NAC, with its deep-reaching eastward velocities. These results add to growing evidence that a significant fraction of ISOW exits the Iceland Basin by routes other than the CGFZ.U.S. National Science Foundation Grant Number: OCE-0926656; Woods Hole Oceanographic Institution2018-03-0

Mesoscale eddies in the Gulf of Aden and their impact on the spreading of Red Sea Outflow Water

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 96 (2012): 14-39, doi:10.1016/j.pocean.2011.09.003.The Gulf of Aden (GOA) in the northwestern Indian Ocean is the receiving basin for Red Sea Outflow Water (RSOW), one of the World’s few high-salinity dense overflows, but relatively little is known about spreading pathways and transformation of RSOW through the gulf. Here we combine historical data, satellite altimetry, new synoptic hydrographic surveys and the first in situ direct observations of subsurface currents in the GOA to identify the most important processes in the spreading of RSOW. The new in situ data sets were collected in 2001-2003 as part of the Red Sea Outflow Experiment (REDSOX) and consist of two CTD/LADCP Surveys and 49 one-year trajectories from acoustically tracked floats released at the depth of RSOW. The results indicate that the prominent positive and negative sea level anomalies frequently observed in the GOA with satellite altimetry are associated with anticyclonic and cyclonic eddies that often reach to at least 1000 m depth, i.e., through the depth range of equilibrated RSOW. The eddies dominate RSOW spreading pathways and help to rapidly mix the outflow water with the background. Eddies in the central and eastern gulf are basin-scale (~250-km diameter) and have maximum azimuthal speeds of about 30 cm/s at the RSOW level. In the western gulf, smaller eddies not detectable with satellite altimetry appear to form as the larger westward-propagating eddies impale themselves on the high ridges flanking the Tadjura Rift. Both the hydrographic and Lagrangian observations show that eddies originating outside the gulf often transport a core of much cooler, fresher water from the Arabian Sea all the way to the western end of the GOA, where the highest-salinity outflow water is found. This generates large vertical and horizontal gradients of temperature and salinity, setting up favorable conditions for salt fingering and diffusive convection. Both of these mixing processes were observed to be active in the gulf. Two new annually appearing anticyclonic eddies are added to the previously identified Gulf of Aden Eddy (GAE; Prasad and Ikeda, 2001) and Somali Current Ring (SCR; Fratantoni et al., 2006). These are the Summer Eddy (SE) and the Lee Eddy (LE), both of which form at the beginning of the summer monsoon when strong southwest winds blowing through Socotra Passage effectively split the GAE into two smaller eddies. The SE strengthens as it propagates westward deeper in the GOA, while the Lee Eddy remains stationary in the lee of Socotra Island. Both eddies are strengthened or sustained by Ekman convergence associated with negative wind stress curl patches caused by wind jets through or around high orography. The annual cycle in the appearance, propagation and demise of these new eddies and those described in earlier work is documented to provide a comprehensive view of the most energetic circulation features in the GOA. The observations contain little evidence of features that have been shown previously to be important in the spreading of Mediterranean Outflow Water (MOW) in the North Atlantic, namely a wall-bounded subsurface jet (the Mediterranean Undercurrent ) and submesoscale coherent lenses containing a core of MOW (‘meddies’). This is attributed to the fact that the RSOW enters the open ocean on a western boundary. High background eddy kinetic energy typical of western boundary regimes will tend to shear apart submesoscale eddies and boundary undercurrents. Even if a submesoscale lens of RSOW did form in the GOA, westward self-propagation would transport the eddy and its cargo of outflow water back toward, rather than away from, its source.This work was supported by grants to the Woods Hole Oceanographic Institution by the U.S. National Science Foundation

Warm water pathways in the northeastern North Atlantic ACCE RAFOS float data report November 1996 - November 1999

This is the final data report of all acoustically tracked RAFOS float data collected by the Woods Hole Oceanographic Institution in 1996-1999 during the Atlantic Climate Change Experiment (ACCE). The RAFOS float component of ACCE, entitled "Warm Water Pathways and Intergyre Exchange in the Northeastern North Atlantic," was designed to measure the warm water currents entering the northeastern North Atlantic which become the source of intermediate and deep waters in the subpolar region. The experiment was comprised of three RAFOS float deployments on the R/V Knorr: the first in fall 1996 along the continental slope seaward of Porcupine Bank, the second in spring 1997 along the mid-Atlantic Ridge, and the final deployment in fall 1997 along both the Ridge and the Bank. Seventy floats were deployed, 13 RAFOS and 2 ALFOS in fall 1996, 14 RAFOS in spring 1997, and 41 RAFOS in fall 1997. The isobaric ALFOS floats were ballasted for 800 decibars and were launched to monitor the regions' sound sources during the experiment. The RAFOS floats were isopycnal and ballasted for the 27.5 sigma-t surface to target the intermediate-depth North Atlantic and Poleward Eastern Boundary Currents. The objectives of the Lagrangian float study were (1) to provide a quantitative description of the bifurcation of the North Atlantic Current east of the Mid-Atlantic Ridge, (2) to assess the importance of meridional eddy fluxes, compared to large-scale advection, in the northward flux of heat and salt in the northeastern North Atlantic, and (3) to establish the degree of continuity of the Poleward Eastern Boundary Current as it flows to the entrance of the Norwegian Sea and the fate of the Mediterranean Outflow Water carried by this current.Funding was provided by the National Science Foundation under Grant Number OCE-9831877

ChIP–seq and beyond: new and improved methodologies to detect and characterize protein–DNA interactions

Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) detect protein-DNA binding events and chemical modifications of histone proteins. Challenges in the standard ChIP-seq protocol have motivated recent enhancements in this approach, such as reducing the number of cells required and increasing the resolution. Complementary experimental approaches – for example DNaseI hypersensitive site mapping and analysis of chromatin interactions mediated by particular proteins - provide additional information about DNA-binding proteins and their function. These data are now being used to identify variability in the functions of DNA-binding proteins across genomes and individuals. In this Review, I describe the latest advances in methods to detect and functionally characterize DNA-bound proteins

Red Sea Outflow Experiment (REDSOX) : DLD2 RAFOS float data report February 2001 - March 2003

This is the final data report of all acoustically tracked second-generation Deep Lagrangian Drifter (DLD2) RAFOS float data collected by the Woods Hole Oceanographic Institution in 2001-2003 during the Red Sea Outflow Experiment (REDSOX). The float component of REDSOX was comprised of two deployments on the R/V Knorr and R/V Ewing: the first in February-March 2001, with 26 floats, and the second in August-September 2001, with 27 floats. The isobaric floats were ballasted for 650 decibars to target the intermediate-depth, high-salinity outflow waters from the Red Sea. The objectives of the Lagrangian float study were (1) to identify the spreading pathways of the equilibrated Red Sea outflow, and to quantify the velocities and eddy variability typical of this outflow and of the background oceanic environment in the Gulf of Aden, and (2) to identify and describe the mesoscale processes which contribute to the seaward transport of Red Sea Overflow Water properties through the Gulf of Aden and into the western Indian Ocean. In addition to floats activated and launched during the two cruises, four time-series sites were chosen for dual-release float moorings. The dual-release floats were released every two months between cruises and every two months after the second cruise, with the final release in March 2002. A pirate attack on the R/V Ewing forced some modification of the float deployment plan during the second cruise.Funding was provided by the National Science Foundation under Grant Number OCE-9818464

Seasonal and interannual variations of Irminger ring formation and boundary–interior heat exchange in FLAME

Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1717-1734, doi:10.1175/JPO-D-15-0124.1.The contribution of warm-core anticyclones shed by the Irminger Current off West Greenland, known as Irminger rings, to the restratification of the upper layers of the Labrador Sea is investigated in the 1/12° Family of Linked Atlantic Models Experiment (FLAME) model. The model output, covering the 1990–2004 period, shows strong similarities to observations of the Irminger Current as well as ring observations at a mooring located offshore of the eddy formation region in 2007–09. An analysis of fluxes in the model shows that while the majority of heat exchange with the interior indeed occurs at the site of the Irminger Current instability, the contribution of the coherent Irminger rings is modest (18%). Heat is provided to the convective region mainly through noncoherent anomalies and enhanced local mixing by the rings facilitating further exchange between the boundary and interior. The time variability of the eddy kinetic energy and the boundary to interior heat flux in the model are strongly correlated to the density gradient between the dense convective region and the more buoyant boundary current. In FLAME, the density variations of the boundary current are larger than those of the convective region, thereby largely controlling changes in lateral fluxes. Synchronous long-term trends in temperature in the boundary and the interior over the 15-yr simulation suggest that the heat flux relative to the temperature of the interior is largely steady on these time scales.The authors were supported in this work by the U.S. National Science Foundation

Variability of the Iceland‐Scotland overflow water transport through the Charlie‐Gibbs fracture zone : results from an eddying simulation and observations

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 123 (2018): 5808-5823, doi:10.1029/2018JC013895.Observations show that the westward transport of the Iceland‐Scotland overflow water (ISOW) through the Charlie‐Gibbs Fracture Zone (CGFZ) is highly variable. This study examines (a) where this variability comes from and (b) how it is related to the variability of ISOW transport at upstream locations in the Iceland Basin and other ISOW flow pathways. The analyses are based on a 35‐year 1/12° eddying Atlantic simulation that represents well the main features of the observed ISOW in the area of interest, in particular, the transport variability through the CGFZ. The results show that (a) the variability of the ISOW transport is closely correlated with that of the barotropic transports in the CGFZ associated with the meridional displacement of the North Atlantic Current front and is possibly induced by fluctuations of large‐scale zonal wind stress in the Western European Basin east of the CGFZ; (b) the variability of the ISOW transport is increased by a factor of 3 from the northern part of the Iceland Basin to the CGFZ region and transport time series at these two locations are not correlated, further suggesting that the variability at the CGFZ does not come from the upstream source; and (c) the variability of the ISOW transport at the CGFZ is strongly anticorrelated to that of the southward ISOW transport along the eastern flank of the Mid‐Atlantic Ridge, suggesting an out‐of‐phase covarying transport between these two ISOW pathways.Woods Hole Oceanographic Institution; National Oceanic and Atmospheric Administration Grant Number: NA15OAR4310088; U.S. National Science Foundation Grant Numbers: 1537136, OCE‐09266562019-02-2

Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation

A significant number of human X-linked genes escape X chromosome inactivation and are thus expressed from both the active and inactive X chromosomes. The basis for escape from inactivation and the potential role of the X chromosome primary DNA sequence in determining a gene's X inactivation status is unclear. Using a combination of the X chromosome sequence and a comprehensive X inactivation profile of more than 600 genes, two independent yet complementary approaches were used to systematically investigate the relationship between X inactivation and DNA sequence features. First, statistical analyses revealed that a number of repeat features, including long interspersed nuclear element (LINE) and mammalian-wide interspersed repeat repetitive elements, are significantly enriched in regions surrounding transcription start sites of genes that are subject to inactivation, while Alu repetitive elements and short motifs containing ACG/CGT are significantly enriched in those that escape inactivation. Second, linear support vector machine classifiers constructed using primary DNA sequence features were used to correctly predict the X inactivation status for >80% of all X-linked genes. We further identified a small set of features that are important for accurate classification, among which LINE-1 and LINE-2 content show the greatest individual discriminatory power. Finally, as few as 12 features can be used for accurate support vector machine classification. Taken together, these results suggest that features of the underlying primary DNA sequence of the human X chromosome may influence the spreading and/or maintenance of X inactivation