ORCID Profile
0000-0002-3393-2459
Current Organisation
University of Amsterdam
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-2023
DOI: 10.1200/JCO.22.01978
Abstract: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS 313 ) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS 313 with clinicopathologic characteristics of, and survival following, breast cancer. Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS 313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS 313 (continuous, per standard deviation) with overall survival (OS) and breast cancer–specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment. The PRS 313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS 313 was associated with lower grade, hormone receptor–positive status, and smaller tumor size. In MINDACT, PRS 313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS 313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent. An increased PRS 313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS 313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS 313 as increasing PRS 313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
Publisher: EDP Sciences
Date: 07-2021
DOI: 10.1051/0004-6361/202140626
Abstract: Context. The nature of circumstellar envelopes (CSEs) around Cepheids is a matter of ongoing debate. The physical origin of their infrared (IR) excess could be shown to either be made up of a shell of ionized gas, a dust envelope, or a combination of both. Aims. This study is aimed at constraining the geometry and the IR excess of the environment of the bright long-period Cepheid ℓ Car ( P = 35.5 days) at mid-IR wavelengths in order to understand its physical nature. Methods. We first used photometric observations in various bands (from the visible domain to the infrared) and Spitzer Space Telescope spectroscopy to constrain the IR excess of ℓ Car. Then we analyzed the VLTI/MATISSE measurements at a specific phase of observation in order to determine the flux contribution as well as the size and shape of the environment of the star in the L band. Finally, we tested the hypothesis of a shell of ionized gas in order to model the IR excess. Results. We report the first detection in the L band of a centro-symmetric extended emission around ℓ Car, of about 1.7 R ⋆ in full width at half maximum, producing an excess of about 7.0% in this band.This latter value is used to calibrate the IR excess found when comparing the photometric observations in various bands and quasi-static atmosphere models. In the N band, there is no clear evidence for dust emission from VLTI/MATISSE correlated flux and Spitzer data. On the other side, the modeled shell of ionized gas implies a more compact CSE (1.13 ± 0.02 R ⋆ ) that is also fainter (IR excess of 1% in the L band). Conclusions. We provide new evidence supporting a compact CSE for ℓ Car and we demonstrate the capabilities of VLTI/MATISSE for determining common properties of CSEs. While the compact CSE of ℓ Car is likely to be of a gaseous nature, the tested model of a shell of ionized gas is not able to simultaneously reproduce the IR excess and the interferometric observations. Further Galactic Cepheid observations with VLTI/MATISSE are necessary for determining the properties of CSEs, which may also depend on both the pulsation period and the evolutionary state of the stars.
Publisher: EDP Sciences
Date: 02-2022
DOI: 10.1051/0004-6361/202142514
Abstract: Context. VX Sgr is a cool, evolved, and luminous red star whose stellar parameters are difficult to determine, which affects its classification. Aims. We aim to spatially resolve the photospheric extent as well as the circumstellar environment. Methods. We used interferometric observations obtained with the MATISSE instrument in the L (3–4 μm), M (4.5–5 μm), and N (8–13 μm) bands. We reconstructed monochromatic images using the MIRA software. We used 3D radiation-hydrodynamics simulations carried out with CO 5 BOLD and a uniform disc model to estimate the apparent diameter and interpret the stellar surface structures. Moreover, we employed the radiative transfer codes OPTIM3D and RADMC3D to compute the spectral energy distribution for the L , M , and N bands, respectively. Results. MATISSE observations unveil, for the first time, the morphology of VX Sgr across the L , M , and N bands. The reconstructed images show a complex morphology with brighter areas whose characteristics depend on the wavelength probed. We measured the angular diameter as a function of the wavelength and showed that the photospheric extent in the L and M bands depends on the opacity through the atmosphere. In addition to this, we also concluded that the observed photospheric inhomogeneities can be interpreted as convection-related surface structures. The comparison in the N band yielded a qualitative agreement between the N -band spectrum and simple dust radiative transfer simulations. However, it is not possible to firmly conclude on the interpretation of the current data because of the difficulty in constraing the model parameters using the limited accuracy of our absolute flux calibration. Conclusions. MATISSE observations and the derived reconstructed images unveil the appearance of VX Sgr’s stellar surface and circumstellar environment across a very large spectral domain for the first time.
Publisher: EDP Sciences
Date: 07-2021
DOI: 10.1051/0004-6361/202038806
Abstract: Context. Large surveys with new-generation high-contrast imaging instruments are needed to derive the frequency and properties of exoplanet populations with separations from ~5 to 300 au. A careful assessment of the stellar properties is crucial for a proper understanding of when, where, and how frequently planets form, and how they evolve. The sensitivity of detection limits to stellar age makes this a key parameter for direct imaging surveys. Aims. We describe the SpHere INfrared survey for Exoplanets (SHINE), the largest direct imaging planet-search c aign initiated at the VLT in 2015 in the context of the SPHERE Guaranteed Time Observations of the SPHERE consortium. In this first paper we present the selection and the properties of the complete s le of stars surveyed with SHINE, focusing on the targets observed during the first phase of the survey (from February 2015 to February 2017). This early s le composed of 150 stars is used to perform a preliminary statistical analysis of the SHINE data, deferred to two companion papers presenting the survey performance, main discoveries, and the preliminary statistical constraints set by SHINE. Methods. Based on a large database collecting the stellar properties of all young nearby stars in the solar vicinity (including kinematics, membership to moving groups, isochrones, lithium abundance, rotation, and activity), we selected the original s le of 800 stars that were ranked in order of priority according to their sensitivity for planet detection in direct imaging with SPHERE. The properties of the stars that are part of the early statistical s le wererevisited, including for instance measurements from the Gaia Data Release 2. Rotation periods were derived for the vast majority of the late-type objects exploiting TESS light curves and dedicated photometric observations. Results. The properties of in idual targets and of the s le as a whole are presented.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2022
DOI: 10.1038/S41586-021-04311-7
Abstract: In the widely accepted 'unified model'
Publisher: EDP Sciences
Date: 07-2021
DOI: 10.1051/0004-6361/202038107
Abstract: The SpHere INfrared Exoplanet (SHINE) project is a 500-star survey performed with SPHERE on the Very Large Telescope for the purpose of directly detecting new substellar companions and understanding their formation and early evolution. Here we present an initial statistical analysis for a subs le of 150 stars spanning spectral types from B to M that are representative of the full SHINE s le. Our goal is to constrain the frequency of substellar companions with masses between 1 and 75 M Jup and semimajor axes between 5 and 300 au. For this purpose, we adopt detection limits as a function of angular separation from the survey data for all stars converted into mass and projected orbital separation using the BEX-COND-hot evolutionary tracks and known distance to each system. Based on the results obtained for each star and on the 13 detections in the s le, we use a Markov chain Monte Carlo tool to compare our observations to two different types of models. The first is a parametric model based on observational constraints, and the second type are numerical models that combine advanced core accretion and gravitational instability planet population synthesis. Using the parametric model, we show that the frequencies of systems with at least one substellar companion are 23.0 −9.7 +13.5 , 5.8 −2.8 +4.7 , and 12.6 −7.1 +12.9 % for BA, FGK, and M stars, respectively. We also demonstrate that a planet-like formation pathway probably dominates the mass range from 1–75 M Jup for companions around BA stars, while for M dwarfs, brown dwarf binaries dominate detections. In contrast, a combination of binary star-like and planet-like formation is required to best fit the observations for FGK stars. Using our population model and restricting our s le to FGK stars, we derive a frequency of 5.7 −2.8 +3.8 %, consistent with predictions from the parametric model. More generally, the frequency values that we derive are in excellent agreement with values obtained in previous studies.
Publisher: EDP Sciences
Date: 03-2022
DOI: 10.1051/0004-6361/202141785
Abstract: Context. Optical interferometry is at a key development stage. The Very Large Telescope Interferometer (VLTI) has established a stable, robust infrastructure for long-baseline interferometry that is usable by general astronomical observers. The present second-generation instruments offer a wide wavelength coverage and improved performance. Their sensitivity and measurement accuracy lead to data and images of high reliability. Aims. We have developed the Multi AperTure mid-Infrared SpectroScopic Experiment (MATISSE) to access, for the first time, high resolution imaging in a wide spectral domain. Many front-line topics are explored with this new equipment, including: stellar activity and mass loss planet formation and evolution in the gas and dust disks around young stars and environment interaction and accretion processes around super massive black holes in active galactic nuclei. Methods. The instrument is a spectro-interferometric imager in the transmission windows called L , M , and N , from 2.8 to 13.0 microns, combining four optical beams from the VLTI’s unit or auxiliary telescopes. Its concept, related observing procedure, data reduction, and calibration approach, is the product of 30 years of instrumental research and has benefitted from the expertise developed in the frame of the VLTI’s first generation instruments. The instrument utilises a multi-axial beam combination that delivers spectrally dispersed fringes. The signal provides the following quantities at several spectral resolutions: photometric flux, coherent fluxes, visibilities, closure phases, wavelength differential visibilities and phases, and aperture-synthesis imaging. Results. This article provides an overview of the physical principle of the instrument and its functionalities. The motivation of the choice of the instrumental concept and the characteristics of the delivered signal are detailed with a description of the observing modes and of their performance limit. MATISSE offers four spectral resolutions in L & M bands, namely 30, 500, 1000 and 3400, and 30 and 220 in the N band, and it provides an angular resolution down to 3 mas for the shortest wavelengths. The MATISSE stand-alone sensitivity limits are 60 mJy in L and 300 mJy in N . The paper gives details of the sensitivity limits for the different measurables and their related precision criteria, considering telescope configurations and spectral resolutions. We also discuss the gain provided with the GRA4MAT fringe tracker. An ensemble of data and reconstructed images illustrate the first acquired key observations. Conclusions. The instrument has been in operation at Cerro Paranal, ESO, Chile, since 2018, and has been open for science use by the international community since April 2019. The first scientific results are being published now.
Publisher: American Astronomical Society
Date: 08-2017
Publisher: EDP Sciences
Date: 08-2021
DOI: 10.1051/0004-6361/202141175
Abstract: Context. Carbon is one of the most abundant components in the Universe. While silicates have been the main focus of solid phase studies in protoplanetary discs (PPDs), little is known about the solid carbon content especially in the planet-forming regions (~0.1–10 au). Fortunately, several refractory carbonaceous species present C-H bonds (such as hydrogenated nano-diamond and amorphous carbon as well as polycyclic aromatic hydrocarbons), which generate infrared (IR) features that can be used to trace the solid carbon reservoirs. The new mid-IR instrument MATISSE, installed at the Very Large Telescope Interferometer (VLTI), can spatially resolve the inner regions (~1–10 au) of PPDs and locate, down to the au-scale, the emission coming from carbon grains. Aims. Our aim is to provide a consistent view on the radial structure, down to the au-scale, as well as basic physical properties and the nature of the material responsible for the IR continuum emission in the inner disk region around HD 179218. Methods. We implemented a temperature-gradient model to interpret the disk IR continuum emission, based on a multiwavelength dataset comprising a broadband spectral energy distribution and VLTI H -, L -, and N -bands interferometric data obtained in low spectral resolution. Then, we added a ring-like component, representing the carbonaceous L -band features-emitting region, to assess its detectability in future higher spectral resolution observations employing mid-IR interferometry. Results. Our temperature-gradient model can consistently reproduce our dataset. We confirmed a spatially extended inner 10 au emission in H - and L -bands, with a homogeneously high temperature (~1700 K), which we associate with the presence of stochastically heated nano-grains. On the other hand, the N -band emitting region presents a ring-like geometry that starts at about 10 au with a temperature of 400 K. Moreover, the existing low resolution MATISSE data exclude the presence of aromatic carbon grains (i.e., producing the 3.3 μm feature) in close proximity tothe star (≲1 au). Future medium spectral resolution MATISSE data will confirm their presence at larger distances. Conclusions. Our best-fit model demonstrates the presence of two separated dust populations: nano-grains that dominate the near- to mid-IR emission in the inner 10 au region and larger grains that dominate the emission outward. The presence of such nano-grains in the highly irradiated inner 10 au region of HD 179218 requires a replenishment process. Considering the expected lifetime of carbon nano-grains from The Heterogeneous dust Evolution Model for Interstellar Solids (THEMIS model), the estimated disk accretion inflow of HD 179218 could significantly contribute to feed the inner 10 au region in nano-grains.Moreover, we also expect a local regeneration of those nano-grains by the photo-fragmentation of larger aggregates.
Publisher: EDP Sciences
Date: 09-2017
DOI: 10.1051/0004-6361/201731152
Abstract: Aims. The SHINE program is a high-contrast near-infrared survey of 600 young, nearby stars aimed at searching for and characterizing new planetary systems using VLT/SPHERE’s unprecedented high-contrast and high-angular-resolution imaging capabilities. It is also intended to place statistical constraints on the rate, mass and orbital distributions of the giant planet population at large orbits as a function of the stellar host mass and age to test planet-formation theories. Methods. We used the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-contrast coronagraphic differential near-infrared images and spectra of the young A2 star HIP 65426. It is a member of the ~17 Myr old Lower Centaurus-Crux association. Results. At a separation of 830 mas (92 au projected) from the star, we detect a faint red companion. Multi-epoch observations confirm that it shares common proper motion with HIP 65426. Spectro-photometric measurements extracted with IFS and IRDIS between 0.95 and 2.2 μ m indicate a warm, dusty atmosphere characteristic of young low-surface-gravity L5-L7 dwarfs. Hot-start evolutionary models predict a luminosity consistent with a 6–12 M Jup , T eff = 1300–1600 K and R = 1.5 ± 0.1 R Jup giant planet. Finally, the comparison with Exo-REM and PHOENIX BT-Settl synthetic atmosphere models gives consistent effective temperatures but with slightly higher surface gravity solutions of log ( g ) = 4.0–5.0 with smaller radii (1.0–1.3 R Jup ). Conclusions. Given its physical and spectral properties, HIP 65426 b occupies a rather unique placement in terms of age, mass, and spectral-type among the currently known imaged planets. It represents a particularly interesting case to study the presence of clouds as a function of particle size, composition, and location in the atmosphere, to search for signatures of non-equilibrium chemistry, and finally to test the theory of planet formation and evolution.
Publisher: EDP Sciences
Date: 2019
DOI: 10.1051/0004-6361/201834302
Abstract: Context. With an orbital distance comparable to that of Saturn in the solar system, β Pictoris b is the closest (semi-major axis ≃9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to β Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet’s orbital parameters. Aims . We aimed at further constraining β Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta β Pictoris b since first light of the instrument in 2014. Results . We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected β Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30° in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 ± 0.5 au (1 σ ), it definitely excludes previously reported possible long orbital periods, and excludes β Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
Publisher: EDP Sciences
Date: 03-2021
DOI: 10.1051/0004-6361/202039400
Abstract: Context. A complex environment exists in the inner few astronomical units of planet-forming disks. High-angular-resolution observations play a key role in our understanding of the disk structure and the dynamical processes at work. Aims. In this study we aim to characterize the mid-infrared brightness distribution of the inner disk of the young intermediate-mass star HD 163296 from early VLTI/MATISSE observations taken in the L - and N -bands. We put special emphasis on the detection of potential disk asymmetries. Methods. We use simple geometric models to fit the interferometric visibilities and closure phases. Our models include a smoothed ring, a flat disk with an inner cavity, and a 2D Gaussian. The models can account for disk inclination and for azimuthal asymmetries as well. We also perform numerical hydrodynamical simulations of the inner edge of the disk. Results. Our modeling reveals a significant brightness asymmetry in the L -band disk emission. The brightness maximum of the asymmetry is located at the NW part of the disk image, nearly at the position angle of the semimajor axis. The surface brightness ratio in the azimuthal variation is 3.5 ± 0.2. Comparing our result on the location of the asymmetry with other interferometric measurements, we confirm that the morphology of the r 0.3 au disk region is time-variable. We propose that this asymmetric structure, located in or near the inner rim of the dusty disk, orbits the star. To find the physical origin of the asymmetry, we tested a hypothesis where a vortex is created by Rossby wave instability, and we find that a unique large-scale vortex may be compatible with our data. The half-light radius of the L -band-emitting region is 0.33 ±0.01 au, the inclination is 52° −7° +5° , and the position angle is 143° ± 3°. Our models predict that a non-negligible fraction of the L -band disk emission originates inside the dust sublimation radius for μ m-sized grains. Refractory grains or large (≳10 μ m-sized) grains could be the origin of this emission. N -band observations may also support a lack of small silicate grains in the innermost disk ( r ≲ 0.6 au), in agreement with our findings from L -band data.
Publisher: EDP Sciences
Date: 07-2018
DOI: 10.1051/0004-6361/201832650
Abstract: We report the discovery of a bright, brown dwarf companion to the star HIP 64892, imaged with VLT/SPHERE during the SHINE exoplanet survey. The host is a B9.5V member of the Lower-Centaurus-Crux subgroup of the Scorpius Centaurus OB association. The measured angular separation of the companion (1.2705 ± 0.0023 ” ) corresponds to a projected distance of 159 ± 12 AU. We observed the target with the dual-band imaging and long-slit spectroscopy modes of the IRDIS imager to obtain its spectral energy distribution (SED) and astrometry. In addition, we reprocessed archival NACO L -band data, from which we also recover the companion. Its SED is consistent with a young ( Myr), low surface gravity object with a spectral type of M9 γ ± 1. From comparison with the BT-Settl atmospheric models we estimate an effective temperature of T eff = 2600 ± 100 K, and comparison of the companion photometry to the COND evolutionary models yields a mass of ~29−37 M J at the estimated age of 16 −7 +15 Myr for the system. The star HIP 64892 is a rare ex le of an extreme-mass ratio system ( q ~ 0.01) and will be useful for testing models relating to the formation and evolution of such low-mass objects.
Publisher: EDP Sciences
Date: 02-2020
DOI: 10.1051/0004-6361/201936641
Abstract: Aims. RefPlanets is a guaranteed time observation programme that uses the Zurich IMaging POLarimeter (ZIMPOL) of Spectro-Polarimetric High-contrast Exoplanet REsearch instrument at the Very Large Telescope to perform a blind search for exoplanets in wavelengths from 600 to 900 nm. The goals of this study are the characterisation of the unprecedented high polarimetic contrast and polarimetric precision capabilities of ZIMPOL for bright targets, the search for polarised reflected light around some of the closest bright stars to the Sun, and potentially the direct detection of an evolved cold exoplanet for the first time. Methods. For our observations of α Cen A and B, Sirius A, Altair, ɛ Eri and τ Ceti we used the polarimetricdifferential imaging (PDI) mode of ZIMPOL which removes the speckle noise down to the photon noise limit for angular separations ≿0.6′′. We describe some of the instrumental effects that dominate the noise for smaller separations and explain how to remove these additional noise effects in post-processing. We then combine PDI with angular differential imaging as a final layer of post-processing to further improve the contrast limits of our data at these separations. Results. For good observing conditions we achieve polarimetric contrast limits of 15.0–16.3 mag at the effective inner working angle of ~0.13′′, 16.3–18.3 mag at 0.5′′, and 18.8–20.4 mag at 1.5′′. The contrast limits closer in (≾0.6′′) display a significant dependence on observing conditions, while in the photon-noise-dominated regime (≿0.6′′) the limits mainly depend on the brightness of the star and the total integration time. We compare our results with contrast limits from other surveys and review the exoplanet detection limits obtained with different detection methods. For all our targets we achieve unprecedented contrast limits. Despite the high polarimetric contrasts we are not able to find any additional companions or extended polarised light sources in the data obtained so far.
Publisher: EDP Sciences
Date: 06-2015
Publisher: Springer Science and Business Media LLC
Date: 21-07-2023
DOI: 10.1038/S41467-023-39996-Z
Abstract: Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from ,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.
Publisher: EDP Sciences
Date: 16-02-2016
Publisher: Research Square Platform LLC
Date: 03-02-2023
DOI: 10.21203/RS.3.RS-2377863/V1
Abstract: Worldwide, there is a growing proportion of women who are overweight or obese. While obesity has been associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet the impact of adiposity (abnormal or excess body fat) on BC biology remains understudied in humans. This retrospective study aimed to investigate how the biology of primary BC would differ according to patients’ body mass index (BMI). We examined clinicopathological data (including BMI at the time of diagnosis) and molecular data (including genomic, bulk and single-cell transcriptomic data) of treatment-naïve (early stage) BC patients from five cohorts (N = 2071). We identified several genomic alterations considered actionable or of potential clinical relevance which had a different prevalence in overweight or obese patients compared to lean patients, for instances, less PIK3CA gene mutations, and more CCND1, CCNE1 and IGFR1 lifications. Moreover, we found evidence supporting an ageing accelerating effect of obesity at the genetic level, through its association with an age-associated mutational signature. We showed that BMI-associated differences in transcriptomic profile were subtle at the bulk resolution while single cell profiling allowed detection of more pronounced changes in different cell compartments. Investigation at the single cell resolution revealed an elevated and unresolved inflammation of the BC tumor microenvironment (TME) associated with obesity, which had distinct characteristics contingent on the estrogen receptor status. Collectively, analyses at both genomic and transcriptomic levels implied that obesity is associated with an inflammaging-like phenotype of the TME. Our results indicate that patient adiposity might play a significant role in the heterogeneity of BC and should be considered in the context of precision medicine.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
DOI: 10.1038/S42003-020-1111-1
Abstract: Gene expression data obtained in large studies hold great promises for discovering disease signatures or subtypes through data analysis. It is also prone to technical variation, whose removal is essential to avoid spurious discoveries. Because this variation is not always known and can be confounded with biological signals, its removal is a challenging task. Here we provide a step-wise procedure and comprehensive analysis of the MINDACT microarray dataset. The MINDACT trial enrolled 6693 breast cancer patients and prospectively validated the gene expression signature MammaPrint for outcome prediction. The study also yielded a full-transcriptome microarray for each tumor. We show for the first time in such a large dataset how technical variation can be removed while retaining expected biological signals. Because of its unprecedented size, we hope the resulting adjusted dataset will be an invaluable tool to discover or test gene expression signatures and to advance our understanding of breast cancer.
No related grants have been discovered for Carsten Dominik.