| 1. |
- Vallenari, A., et al.
(author)
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Gaia Data Release 3: Summary of the content and survey properties
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. We present the third data release of the European Space Agency's Gaia mission, Gaia DR3. This release includes a large variety of new data products, notably a much expanded radial velocity survey and a very extensive astrophysical characterisation of Gaia sources.Aims. We outline the content and the properties of Gaia DR3, providing an overview of the main improvements in the data processing in comparison with previous data releases (where applicable) and a brief discussion of the limitations of the data in this release.Methods. The Gaia DR3 catalogue is the outcome of the processing of raw data collected with the Gaia instruments during the first 34 months of the mission by the Gaia Data Processing and Analysis Consortium.Results. The Gaia DR3 catalogue contains the same source list, celestial positions, proper motions, parallaxes, and broad band photometry in the G, GBP, and G(RP) pass-bands already present in the Early Third Data Release, Gaia EDR3. Gaia DR3 introduces an impressive wealth of new data products. More than 33 million objects in the ranges G(RVS) < 14 and 3100 < T-eff < 14 500, have new determinations of their mean radial velocities based on data collected by Gaia. We provide GRVS magnitudes for most sources with radial velocities, and a line broadening parameter is listed for a subset of these. Mean Gaia spectra are made available to the community. The Gaia DR3 catalogue includes about 1 million mean spectra from the radial velocity spectrometer, and about 220 million low-resolution blue and red prism photometer BP /RP mean spectra. The results of the analysis of epoch photometry are provided for some 10 million sources across 24 variability types. Gaia DR3 includes astrophysical parameters and source class probabilities for about 470 million and 1500 million sources, respectively, including stars, galaxies, and quasars. Orbital elements and trend parameters are provided for some 800 000 astrometric, spectroscopic and eclipsing binaries. More than 150 000 Solar System objects, including new discoveries, with preliminary orbital solutions and individual epoch observations are part of this release. Reflectance spectra derived from the epoch BP /RP spectral data are published for about 60 000 asteroids. Finally, an additional data set is provided, namely the Gaia Andromeda Photometric Survey, consisting of the photometric time series for all sources located in a 5:5 degree radius field centred on the Andromeda galaxy.Conclusions. This data release represents a major advance with respect to Gaia DR2 and Gaia EDR3 because of the unprecedented quantity, quality, and variety of source astrophysical data. To date this is the largest collection of all-sky spectrophotometry, radial velocities, variables, and astrophysical parameters derived from both low- and high-resolution spectra and includes a spectrophotometric and dynamical survey of SSOs of the highest accuracy. The non-single star content surpasses the existing data by orders of magnitude. The quasar host and galaxy light profile collection is the first such survey that is all sky and space based. The astrophysical information provided in Gaia DR3 will unleash the full potential of Gaia's exquisite astrometric, photometric, and radial velocity surveys.
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| 2. |
- Galluccio, L., et al.
(author)
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Gaia Data Release 3: Reflectance spectra of Solar System small bodies
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. The Gaia mission of the European Space Agency (ESA) has been routinely observing Solar System objects (SSOs) since the beginning of its operations in August 2014. The Gaia data release three (DR3) includes, for the first time, the mean reflectance spectra of a selected sample of 60 518 SSOs, primarily asteroids, observed between August 5, 2014, and May 28, 2017. Each reflectance spectrum was derived from measurements obtained by means of the Blue and Red photometers (BP/RP), which were binned in 16 discrete wavelength bands. For every spectrum, the DR3 also contains additional information about the data quality for each band.Aims. We describe the processing of the Gaia spectral data of SSOs, explaining both the criteria used to select the subset of asteroid spectra published in Gaia DR3, and the different steps of our internal validation procedures. In order to further assess the quality of Gaia SSO reflectance spectra, we carried out external validation against SSO reflectance spectra obtained from ground-based and space-borne telescopes and available in the literature; we present our validation approach.Methods. For each selected SSO, an epoch reflectance was computed by dividing the calibrated spectrum observed by the BP/RP at each transit on the focal plane by the mean spectrum of a solar analogue. The latter was obtained by averaging the Gaia spectral measurements of a selected sample of stars known to have very similar spectra to that of the Sun. Finally, a mean of the epoch reflectance spectra was calculated in 16 spectral bands for each SSO.Results. Gaia SSO reflectance spectra are in general agreement with those obtained from a ground-based spectroscopic campaign specifically designed to cover the same spectral interval as Gaia and mimic the illumination and observing geometry characterising Gaia SSO observations. In addition, the agreement between Gaia mean reflectance spectra and those available in the literature is good for bright SSOs, regardless of their taxonomic spectral class. We identify an increase in the spectral slope of S-type SSOs with increasing phase angle. Moreover, we show that the spectral slope increases and the depth of the 1 μm absorption band decreases for increasing ages of S-type asteroid families. The latter can be interpreted as proof of progressive ageing of S-type asteroid surfaces due to their exposure to space weathering effects.
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| 3. |
- Klioner, S. A., et al.
(author)
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Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Journal article (peer-reviewed)abstract
- Context. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue.Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality.Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3).Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13-21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr-1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution.
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| 4. |
- Lindegren, L., et al.
(author)
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Gaia Data Release 3: The extragalactic content
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- The Gaia Galactic survey mission is designed and optimized to obtain astrometry, photometry, and spectroscopy of nearly two billion stars in our Galaxy. Yet as an all-sky multi-epoch survey, Gaia also observes several million extragalactic objects down to a magnitude of G 21 mag. Due to the nature of the Gaia onboard-selection algorithms, these are mostly point-source-like objects. Using data provided by the satellite, we have identified quasar and galaxy candidates via supervised machine learning methods, and estimate their redshifts using the low resolution BP/RP spectra. We further characterise the surface brightness profiles of host galaxies of quasars and of galaxies from pre-defined input lists. Here we give an overview of the processing of extragalactic objects, describe the data products in Gaia DR3, and analyse their properties. Two integrated tables contain the main results for a high completeness, but low purity (50-70%), set of 6.6 million candidate quasars and 4.8 million candidate galaxies. We provide queries that select purer sub-samples of these containing 1.9 million probable quasars and 2.9 million probable galaxies (both 95% purity). We also use high quality BP/RP spectra of 43 thousand high probability quasars over the redshift range 0.05-4.36 to construct a composite quasar spectrum spanning restframe wavelengths from 72 1000 nm.
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| 5. |
- De Ridder, J., et al.
(author)
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Gaia Data Release 3: Pulsations in main sequence OBAF-type stars
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M ≥ 1.3 M⊙) of spectral types O, B, A, or F, known as β Cep, slowly pulsating B (SPB), δ Sct, and γ Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series.Aims. We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the δ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation.Methods. All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The δ Sct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data.Results. We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive period–luminosity relation for δ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of δ Sct stars.Conclusions. The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes.
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| 6. |
- Drimmel, R., et al.
(author)
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Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. With the most recent Gaia data release, the number of sources with complete 6D phase space information (position and velocity) has increased to well over 33 million stars, while stellar astrophysical parameters are provided for more than 470 million sources, and more than 11 million variable stars are identified.Aims. Using the astrophysical parameters and variability classifications provided in Gaia DR3, we selected various stellar populations to explore and identify non-axisymmetric features in the disc of the Milky Way in configuration and velocity space.Methods. Using more about 580 000 sources identified as hot OB stars, together with 988 known open clusters younger than 100 Myr, we mapped the spiral structure associated with star formation 4−5 kpc from the Sun. We selected over 2800 Classical Cepheids younger than 200 Myr that show spiral features extending as far as 10 kpc from the Sun in the outer disc. We also identified more than 8.7 million sources on the red giant branch (RGB), of which 5.7 million have line-of-sight velocities. This later sample allows the velocity field of the Milky Way to be mapped as far as 8 kpc from the Sun, including the inner disc.Results. The spiral structure revealed by the young populations is consistent with recent results using Gaia EDR3 astrometry and source lists based on near-infrared photometry, showing the Local (Orion) Arm to be at least 8 kpc long, and an outer arm consistent with what is seen in HI surveys, which seems to be a continuation of the Perseus arm into the third quadrant. The subset of RGB stars with velocities clearly reveals the large-scale kinematic signature of the bar in the inner disc, as well as evidence of streaming motions in the outer disc that might be associated with spiral arms or bar resonances. A local comparison of the velocity field of the OB stars reveals similarities and differences with the RGB sample.Conclusions. This cursory study of Gaia DR3 data shows there is a rich bounty of kinematic information to be explored more deeply, which will undoubtedly lead us to a clearer understanding of the dynamical nature of the non-axisymmetric structures of the Milky Way.
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| 7. |
- Lindegren, L., et al.
(author)
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Gaia Data Release 3: A golden sample of astrophysical parameters
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. Gaia Data Release 3 (DR3) provides a wealth of new data products for the astronomical community to exploit, including astrophysical parameters for half a billion stars. In this work, we demonstrate the high quality of these data products and illustrate their use in different astrophysical contexts.Aims. We produce homogeneous samples of stars with high-quality astrophysical parameters by exploiting Gaia DR3, while focusing on many regimes across the Hertzsprung-Russell (HR) diagram; spectral types OBA, FGKM, and ultracool dwarfs (UCDs). We also focus on specific subsamples of particular interest to the community: solar analogues, carbon stars, and the Gaia spectrophotometric standard stars (SPSS).Methods. We query the astrophysical parameter tables along with other tables in Gaia DR3 to derive the samples of the stars of interest. We validate our results using the Gaia catalogue itself and by comparison with external data.Results. We produced six homogeneous samples of stars with high-quality astrophysical parameters across the HR diagram for the community to exploit. We first focus on three samples that span a large parameter space: young massive disc stars (OBA; about 3 Million), FGKM spectral type stars (about 3 Million), and UCDs (about 20 000). We provide these sources along with additional information (either a flag or complementary parameters) as tables that are made available in the Gaia archive. We also identify 15 740 bone fide carbon stars and 5863 solar analogues, and provide the first homogeneous set of stellar parameters of the SPSS sample. We demonstrate some applications of these samples in different astrophysical contexts. We use a subset of the OBA sample to illustrate its usefulness in analysing the Milky Way rotation curve. We then use the properties of the FGKM stars to analyse known exoplanet systems. We also analyse the ages of some unseen UCD-companions to the FGKM stars. We additionally predict the colours of the Sun in various passbands (Gaia, 2MASS, WISE) using the solar-analogue sample.Conclusions. Gaia DR3 contains a wealth of new high-quality astrophysical parameters for the community to exploit.
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| 8. |
- Recio-Blanco, A., et al.
(author)
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Gaia Data Release 3: Chemical cartography of the Milky Way
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. The motion of stars has been used to reveal details of the complex history of the Milky Way, in constant interaction with its environment. Nevertheless, to reconstruct the Galactic history puzzle in its entirety, the chemo-physical characterisation of stars is essential. Previous Gaia data releases were supported by a smaller, heterogeneous, and spatially biased mixture of chemical data from ground-based observations.Aims. Gaia Data Release 3 opens a new era of all-sky spectral analysis of stellar populations thanks to the nearly 5.6 million stars observed by the Radial Velocity Spectrometer (RVS) and parametrised by the GSP-Spec module. In this work, we aim to demonstrate the scientific quality of Gaia s Milky Way chemical cartography through a chemo-dynamical analysis of disc and halo populations.Methods. Stellar atmospheric parameters and chemical abundances provided by Gaia DR3 spectroscopy are combined with DR3 radial velocities and EDR3 astrometry to analyse the relationships between chemistry and Milky Way structure, stellar kinematics, and orbital parameters.Results. The all-sky Gaia chemical cartography allows a powerful and precise chemo-dynamical view of the Milky Way with unprecedented spatial coverage and statistical robustness. First, it reveals the strong vertical symmetry of the Galaxy and the flared structure of the disc. Second, the observed kinematic disturbances of the disc seen as phase space correlations and kinematic or orbital substructures are associated with chemical patterns that favour stars with enhanced metallicities and lower [α/Fe] abundance ratios compared to the median values in the radial distributions. This is detected both for young objects that trace the spiral arms and older populations. Several α, iron-peak elements and at least one heavy element trace the thin and thick disc properties in the solar cylinder. Third, young disc stars show a recent chemical impoverishment in several elements. Fourth, the largest chemo-dynamical sample of open clusters analysed so far shows a steepening of the radial metallicity gradient with age, which is also observed in the young field population. Finally, the Gaia chemical data have the required coverage and precision to unveil galaxy accretion debris and heated disc stars on halo orbits through their [α/Fe] ratio, and to allow the study of the chemo-dynamical properties of globular clusters. Conclusions. Gaia DR3 chemo-dynamical diagnostics open new horizons before the era of ground-based wide-field spectroscopic surveys. They unveil a complex Milky Way that is the outcome of an eventful evolution, shaping it to the present day.
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| 9. |
- Schultheis, M., et al.
(author)
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Gaia Data Release 3: Exploring and mapping the diffuse interstellar band at 862 nm
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. Diffuse interstellar bands (DIBs) are common interstellar absorption features in spectroscopic observations but their origins remain unclear. DIBs play an important role in the life cycle of the interstellar medium (ISM) and can also be used to trace Galactic structure.Aims. Here, we demonstrate the capacity of the Gaia-Radial Velocity Spectrometer (RVS) in Gaia DR3 to reveal the spatial distribution of the unknown molecular species responsible for the most prominent DIB at 862 nm in the RVS passband, exploring the Galactic ISM within a few kiloparsecs from the Sun.Methods. The DIBs are measured within the GSP-Spec module using a Gaussian profile fit for cool stars and a Gaussian process for hot stars. In addition to the equivalent widths and their uncertainties, Gaia DR3 provides their characteristic central wavelength, width, and quality flags.Results. We present an extensive sample of 476 117 individual DIB measurements obtained in a homogeneous way covering the entire sky. We compare spatial distributions of the DIB carrier with interstellar reddening and find evidence that DIB carriers are present in a local bubble around the Sun which contains nearly no dust. We characterised the DIB equivalent width with a local density of 0.19 ± 0.04 kpc1 and a scale height of 98.60 8.46+11.10 pc. The latter is smaller than the dust scale height, indicating that DIBs are more concentrated towards the Galactic plane. We determine the rest-frame wavelength with unprecedented precision (?0 = 8620.86 ± 0.019 in air) and reveal a remarkable correspondence between the DIB velocities and the CO gas velocities, suggesting that the 862 nm DIB carrier is related to macro-molecules. Conclusions. We demonstrate the unique capacity of Gaia to trace the spatial structure of the Galactic ISM using the 862 nm DIB.
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| 10. |
- Montegriffo, P., et al.
(author)
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Gaia Data Release 3: The Galaxy in your preferred colours: Synthetic photometry from Gaia low-resolution spectra
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Gaia Data Release 3 provides novel flux-calibrated low-resolution spectrophotometry for ≅220 million sources in the wavelength range 330 nm ≤ λ ≤ 1050 nm (XP spectra). Synthetic photometry directly tied to a flux in physical units can be obtained from these spectra for any passband fully enclosed in this wavelength range. We describe how synthetic photometry can be obtained from XP spectra, illustrating the performance that can be achieved under a range of different conditions - for example passband width and wavelength range - as well as the limits and the problems affecting it. Existing top-quality photometry can be reproduced within a few per cent over a wide range of magnitudes and colour, for wide and medium bands, and with up to millimag accuracy when synthetic photometry is standardised with respect to these external sources. Some examples of potential scientific application are presented, including the detection of multiple populations in globular clusters, the estimation of metallicity extended to the very metal-poor regime, and the classification of white dwarfs. A catalogue providing standardised photometry for ≅2.2×108 sources in several wide bands of widely used photometric systems is provided (Gaia Synthetic Photometry Catalogue; GSPC) as well as a catalogue of ≅105 white dwarfs with DA/non-DA classification obtained with a Random Forest algorithm (Gaia Synthetic Photometry Catalogue for White Dwarfs; GSPC-WD).
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| 11. |
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| 12. |
- Lindegren, Lennart, et al.
(author)
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Gaia Early Data Release 3 : The Gaia Catalogue of Nearby Stars
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Journal article (peer-reviewed)abstract
- Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use.Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue.Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun.Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Rodriguez-Fernandez, B., et al.
(author)
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Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study
- 2022
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Journal article (peer-reviewed)abstract
- Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer's disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE-epsilon 4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF A beta and higher levels of CSF NfL only in APOE-epsilon 4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations.
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| 17. |
- Hedenfalk, I, et al.
(author)
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Gene-expression profiles in hereditary breast cancer
- 2001
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In: New England Journal of Medicine. - 0028-4793. ; 344:8, s. 48-539
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Journal article (peer-reviewed)abstract
- BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles.METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype.RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations.CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.
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| 18. |
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| 19. |
- Fraga, MF, et al.
(author)
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Epigenetic differences arise during the lifetime of monozygotic twins
- 2005
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:30, s. 10604-10609
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Journal article (peer-reviewed)abstract
- Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
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| 20. |
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| 21. |
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| 22. |
- Lund, G, et al.
(author)
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DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E
- 2004
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In: Journal of Biological Chemistry. - 1083-351X. ; 279:28, s. 29147-29154
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Journal article (peer-reviewed)abstract
- The present work investigates the occurrence and significance of aberrant DNA methylation patterns during early stages of atherosclerosis. To this end, we asked whether the genetically atherosclerosis-prone APOEnull mice show any changes in DNA methylation patterns before the appearance of histologically detectable vascular lesion. We exploited a combination of various techniques: DNA fingerprinting, in vitro methyl-accepting assay, 5-methylcytosine quantitation, histone post-translational modification analysis, Southern blotting, and PCR. Our results show that alterations in DNA methylation profiles, including both hyper- and hypomethylation, were present in aortas and PBMC of 4-week-old mutant mice with no detectable atherosclerotic lesion. Sequencing and expression analysis of 60 leukocytic polymorphisms revealed that epigenetic changes involve transcribed genic sequences, as well as repeated interspersed elements. Furthermore, we showed for the first time that atherogenic lipoproteins promote global DNA hypermethylation in a human monocyte cell line. Taken together, our results unequivocally show that alterations in DNA methylation profiles are early markers of atherosclerosis in a mouse model and may play a causative role in atherogenesis.
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| 23. |
- Pérez-Perarnau, Alba, et al.
(author)
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A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins
- 2014
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 53:38, s. 10150-10154
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Journal article (peer-reviewed)abstract
- A new class of small molecules, with an unprecedented trifluorothiazoline scaffold, were synthesized and their pro-apoptotic activity was evaluated. With an EC50 in the low micromolar range, these compounds proved to be potent inducers of apoptosis in a broad spectrum of tumor cell lines, regardless of the functional status of p53. Fast structure-activity relationship studies allowed the preparation of the strongest apoptosis-inducing candidate. Using a high performance affinity purification approach, we identified prohibitins 1 and 2, key proteins involved in the maintenance of cell viability, as the targets for these compounds.
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| 24. |
- Andersen, Gregers Stig Tig, et al.
(author)
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The DEXLIFE study methods : identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals
- 2014
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In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 383-389
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Journal article (peer-reviewed)abstract
- The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.
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| 25. |
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| 26. |
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| 27. |
- Llinàs-Arias, Pere, et al.
(author)
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3-D chromatin conformation, accessibility, and gene expression profiling of triple-negative breast cancer
- 2023
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In: BMC Genomic Data. - : Springer Nature. - 2730-6844. ; 24:1
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Journal article (peer-reviewed)abstract
- Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Unlike other breast cancer subtypes, the scarcity of specific therapies and greater frequencies of distant metastases contribute to its aggressiveness. We aimed to find epigenetic changes that aid in the understanding of the dissemination process of these cancers. Data description: Using CRISPR/Cas9, our experimental approach led us to identify and disrupt an insulator element, IE8, whose activity seemed relevant for cell invasion. The experiments were performed in two well-established TNBC cellular models, the MDA-MB-231 and the MDA-MB-436. To gain insights into the underlying molecular mechanisms of TNBC invasion ability, we generated and characterized high-resolution chromatin interaction (Hi-C) and chromatin accessibility (ATAC-seq) maps in both cell models and complemented these datasets with gene expression profiling (RNA-seq) in MDA-MB-231, the cell line that showed more significant changes in chromatin accessibility. Altogether, our data provide a comprehensive resource for understanding the spatial organization of the genome in TNBC cells, which may contribute to accelerating the discovery of TNBC-specific alterations triggering advances for this devastating disease.
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| 28. |
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| 29. |
- Pawar, Harvinder, et al.
(author)
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Ghost admixture in eastern gorillas
- 2023
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In: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 7:9, s. 1503-1514
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Journal article (peer-reviewed)abstract
- Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.
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| 30. |
- Rosenquist, R, et al.
(author)
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Introduction: Epigenetics in cancer
- 2018
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In: Seminars in cancer biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 51, s. IV-V
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Journal article (other academic/artistic)
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| 31. |
- Shen, Sipeng, et al.
(author)
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A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer
- 2018
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In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:6, s. 913-924
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Journal article (peer-reviewed)abstract
- B-cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated with lower overall survival. The prognostic model based on methylation could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51-2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression was positively correlated with survival in each cohort (HR range, 0.28-0.68), which we confirmed with meta-analysis (HR = 0.61, 95% CI 0.54-0.68). The three CpG probes were all negatively correlated with BTG2 expression. Importantly, an integrative model of BTG2 methylation, expression and clinical information showed better predictive ability in the training set and validation set. In conclusion, the methylation and integrated prognostic signatures based on BTG2 are stable and reliable biomarkers for early-stage NSCLC. They may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future.
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| 32. |
- Vizoso, Miguel, et al.
(author)
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Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
- 2015
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:7, s. 741-
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Journal article (peer-reviewed)abstract
- Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.
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| 33. |
- Wei, Yongyue, et al.
(author)
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Epigenetic modifications inlysine demethylases associate with survival of early-stage NSCLC
- 2018
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In: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 10
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Journal article (peer-reviewed)abstract
- Background: KDMlysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations inKDMgenes and their roles in lung cancer survival.Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites inKDMgenes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation.Results: DNA methylation at sites cg11637544 inKDM2Aand cg26662347 inKDM1Awere in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16-1.50,P = 1.1 × 10-4;HRcg26662347 = 1.88, 95%CI, 1.37-2.60,P = 3.7 × 10-3), and correlated with corresponding gene expression (cg11637544 forKDM2A,P = 1.3 × 10-10; cg26662347 forKDM1A P = 1.5 × 10-5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance.Conclusions: These findings highlight the association between somatic DNA methylation inKDMgenes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.
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| 34. |
- Wouters, Jasper, et al.
(author)
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Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma
- 2017
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:1, s. 1-16
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Journal article (peer-reviewed)abstract
- Background: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses. Methods: We performed a comprehensive DNA methylation analysis during all progression stages of melanoma using Infinium HumanMethylation450 BeadChips on a discovery cohort of benign nevi (n = 14) and malignant melanoma from both primary (n = 33) and metastatic (n = 28) sites, integrating the DNA methylome with gene expression data. We validated the discovered biomarkers in three independent validation cohorts by pyrosequencing and immunohistochemistry. Results: We identified and validated biomarkers for, and pathways involved in, melanoma development (e.g., HOXA9 DNA methylation) and tumor progression (e.g., TBC1D16 DNA methylation). In addition, we determined a prognostic signature with potential clinical applicability and validated PON3 DNA methylation and OVOL1 protein expression as biomarkers with prognostic information independent of tumor thickness and ulceration. Conclusions: Our data underscores the importance of epigenomic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation unleashes dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor development and progression previously unrelated to melanoma, and determined a prognostic signature with potential clinical utility.
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