| 1. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Aguado, D. S., et al.
(author)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
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In: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
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Journal article (peer-reviewed)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 8. |
- Andrews, Gregory, et al.
(author)
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Mammalian evolution of human cis-regulatory elements and transcription factor binding sites
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.
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| 9. |
- Andrews, Timothy, et al.
(author)
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On the Effect of Historical SST Patterns on Radiative Feedback
- 2022
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:18
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Journal article (peer-reviewed)abstract
- We investigate the dependence of radiative feedback on the pattern of sea-surface temperature (SST) change in 14 Atmospheric General Circulation Models (AGCMs) forced with observed variations in SST and sea-ice over the historical record from 1871 to near-present. We find that over 1871–1980, the Earth warmed with feedbacks largely consistent and strongly correlated with long-term climate sensitivity feedbacks (diagnosed from corresponding atmosphere-ocean GCM abrupt-4xCO2 simulations). Post 1980, however, the Earth warmed with unusual trends in tropical Pacific SSTs (enhanced warming in the west, cooling in the east) and cooling in the Southern Ocean that drove climate feedback to be uncorrelated with—and indicating much lower climate sensitivity than—that expected for long-term CO2 increase. We show that these conclusions are not strongly dependent on the Atmospheric Model Intercomparison Project (AMIP) II SST data set used to force the AGCMs, though the magnitude of feedback post 1980 is generally smaller in nine AGCMs forced with alternative HadISST1 SST boundary conditions. We quantify a “pattern effect” (defined as the difference between historical and long-term CO2 feedback) equal to 0.48 ± 0.47 [5%–95%] W m−2 K−1 for the time-period 1871–2010 when the AGCMs are forced with HadISST1 SSTs, or 0.70 ± 0.47 [5%–95%] W m−2 K−1 when forced with AMIP II SSTs. Assessed changes in the Earth's historical energy budget agree with the AGCM feedback estimates. Furthermore satellite observations of changes in top-of-atmosphere radiative fluxes since 1985 suggest that the pattern effect was particularly strong over recent decades but may be waning post 2014.
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| 10. |
- Christmas, Matthew, et al.
(author)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 11. |
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| 12. |
- Gregory, J. M., et al.
(author)
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How accurately can the climate sensitivity to CO2 be estimated from historical climate change?
- 2020
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In: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 54:1-2, s. 129-157
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Journal article (peer-reviewed)abstract
- The equilibrium climate sensitivity (ECS, in K) to CO2 doubling is a large source of uncertainty in projections of future anthropogenic climate change. Estimates of ECS made from non-equilibrium states or in response to radiative forcings other than 2×CO2 are called “effective climate sensitivity” (EffCS, in K). Taking a “perfect-model” approach, using coupled atmosphere–ocean general circulation model (AOGCM) experiments, we evaluate the accuracy with which CO2 EffCS can be estimated from climate change in the “historical” period (since about 1860). We find that (1) for statistical reasons, unforced variability makes the estimate of historical EffCS both uncertain and biased; it is overestimated by about 10% if the energy balance is applied to the entire historical period, 20% for 30-year periods, and larger factors for interannual variability, (2) systematic uncertainty in historical radiative forcing translates into an uncertainty of±30 to 45% (standard deviation) in historical EffCS, (3) the response to the changing relative importance of the forcing agents, principally CO2 and volcanic aerosol, causes historical EffCS to vary over multidecadal timescales by a factor of two. In recent decades it reached its maximum in the AOGCM historical experiment (similar to the multimodel-mean CO2 EffCS of 3.6 K from idealised experiments), but its minimum in the real world (1.6 K for an observational estimate for 1985–2011, similar to the multimodel-mean value for volcanic forcing). The real-world variations mean that historical EffCS underestimates CO2 EffCS by 30% when considering the entire historical period. The difference for recent decades implies that either unforced variability or the response to volcanic forcing causes a much stronger regional pattern of sea surface temperature change in the real world than in AOGCMs. We speculate that this could be explained by a deficiency in simulated coupled atmosphere–ocean feedbacks which reinforce the pattern (resembling the Interdecadal Pacific Oscillation in some respects) that causes the low EffCS. We conclude that energy-balance estimates of CO2 EffCS are most accurate from periods unaffected by volcanic forcing. Atmosphere GCMs provided with observed sea surface temperature for the 1920s to the 1950s, which was such a period, give a range of about 2.0–4.5 K, agreeing with idealised CO2 AOGCM experiments; the consistency is a reason for confidence in this range as an estimate of CO2 EffCS. Unless another explosive volcanic eruption occurs, the first 30 years of the present century may give a more accurate energy-balance historical estimate of this quantity.
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| 13. |
- Rugenstein, Maria, et al.
(author)
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Equilibrium Climate Sensitivity Estimated by Equilibrating Climate Models
- 2020
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:4
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Journal article (peer-reviewed)abstract
- The methods to quantify equilibrium climate sensitivity are still debated. We collect millennial-length simulations of coupled climate models and show that the global mean equilibrium warming is higher than those obtained using extrapolation methods from shorter simulations. Specifically, 27 simulations with 15 climate models forced with a range of CO2 concentrations show a median 17% larger equilibrium warming than estimated from the first 150 years of the simulations. The spatial patterns of radiative feedbacks change continuously, in most regions reducing their tendency to stabilizing the climate. In the equatorial Pacific, however, feedbacks become more stabilizing with time. The global feedback evolution is initially dominated by the tropics, with eventual substantial contributions from the mid-latitudes. Time-dependent feedbacks underscore the need of a measure of climate sensitivity that accounts for the degree of equilibration, so that models, observations, and paleo proxies can be adequately compared and aggregated to estimate future warming.
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| 14. |
- Rugenstein, Maria, et al.
(author)
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LongRunMIP : Motivation and Design for a Large Collection of Millennial-Length AOGCM Simulations
- 2019
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 100:12, s. 2551-2570
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Journal article (peer-reviewed)abstract
- We present a model intercomparison project, LongRunMIP, the first collection of millennial-length (1,000+ years) simulations of complex coupled climate models with a representation of ocean, atmosphere, sea ice, and land surface, and their interactions. Standard model simulations are generally only a few hundred years long. However, modeling the long-term equilibration in response to radiative forcing perturbation is important for understanding many climate phenomena, such as the evolution of ocean circulation, time- and temperature-dependent feedbacks, and the differentiation of forced signal and internal variability. The aim of LongRunMIP is to facilitate research into these questions by serving as an archive for simulations that capture as much of this equilibration as possible. The only requirement to participate in LongRunMIP is to contribute a simulation with elevated, constant CO2 forcing that lasts at least 1,000 years. LongRunMIP is an MIP of opportunity in that the simulations were mostly performed prior to the conception of the archive without an agreed-upon set of experiments. For most models, the archive contains a preindustrial control simulation and simulations with an idealized (typically abrupt) CO2 forcing. We collect 2D surface and top-of-atmosphere fields and 3D ocean temperature and salinity fields. Here, we document the collection of simulations and discuss initial results, including the evolution of surface and deep ocean temperature and cloud radiative effects. As of October 2019, the collection includes 50 simulations of 15 models by 10 modeling centers. The data of LongRunMIP are publicly available. We encourage submissions of more simulations in the future.
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| 15. |
- Sullivan, Patrick F., et al.
(author)
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Leveraging base-pair mammalian constraint to understand genetic variation and human disease
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643, s. 367-
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Journal article (peer-reviewed)abstract
- Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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