| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 2. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 3. |
- Alexandrov, Ludmil B., et al.
(författare)
-
Signatures of mutational processes in human cancer
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
-
Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
|
|
| 4. |
- Calabrese, Claudia, et al.
(författare)
-
Genomic basis for RNA alterations in cancer
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
-
Tidskriftsartikel (refereegranskat)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
|
|
| 5. |
- Barna, Barnabas, et al.
(författare)
-
SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
- 2021
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
-
Tidskriftsartikel (refereegranskat)abstract
- We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
|
|
| 6. |
- Brout, Dillon, et al.
(författare)
-
The Pantheon+ analysis : cosmological constraints
- 2022
-
Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find ΩM = 0.334 ± 0.018 from SNe Ia alone. For a flat w0CDM model, we measure w0 = −0.90 ± 0.14 from SNe Ia alone, H0 = 73.5 ± 1.1 km s−1 Mpc−1 when including the Cepheid host distances and covariance (SH0ES), and w0 = -0.978-+0.0310.024 when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w0waCDM universe, and measure wa = -0.1-+2.00.9 from Pantheon+ SNe Ia alone, H0 = 73.3 ± 1.1 km s−1 Mpc−1 when including SH0ES Cepheid distances, and wa = -0.65-+0.320.28 when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H0 and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
|
|
| 7. |
- Hosseinzadeh, Griffin, et al.
(författare)
-
Weak Mass Loss from the Red Supergiant Progenitor of the Type II SN 2021yja
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 935:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present high-cadence optical, ultraviolet (UV), and near-infrared data of the nearby (D approximate to 23 Mpc) Type II supernova (SN) 2021yja. Many Type II SNe show signs of interaction with circumstellar material (CSM) during the first few days after explosion, implying that their red supergiant (RSG) progenitors experience episodic or eruptive mass loss. However, because it is difficult to discover SNe early, the diversity of CSM configurations in RSGs has not been fully mapped. SN 2021yja, first detected within approximate to 5.4 hours of explosion, shows some signatures of CSM interaction (high UV luminosity and radio and x-ray emission) but without the narrow emission lines or early light-curve peak that can accompany CSM. Here we analyze the densely sampled early light curve and spectral series of this nearby SN to infer the properties of its progenitor and CSM. We find that the most likely progenitor was an RSG with an extended envelope, encompassed by low-density CSM. We also present archival Hubble Space Telescope imaging of the host galaxy of SN 2021yja, which allows us to place a stringent upper limit of less than or similar to 9 M-circle dot; on the progenitor mass. However, this is in tension with some aspects of the SN evolution, which point to a more massive progenitor. Our analysis highlights the need to consider progenitor structure when making inferences about CSM properties, and that a comprehensive view of CSM tracers should be made to give a fuller view of the last years of RSG evolution.
|
|
| 8. |
- Malbet, F., et al.
(författare)
-
Faint objects in motion: the new frontier of high precision astrometry
- 2021
-
Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:3, s. 845-886
-
Tidskriftsartikel (refereegranskat)abstract
- Sky survey telescopes and powerful targeted telescopes play complementary roles in astronomy. In order to investigate the nature and characteristics of the motions of very faint objects, a flexibly-pointed instrument capable of high astrometric accuracy is an ideal complement to current astrometric surveys and a unique tool for precision astrophysics. Such a space-based mission will push the frontier of precision astrometry from evidence of Earth-mass habitable worlds around the nearest stars, to distant Milky Way objects, and out to the Local Group of galaxies. As we enter the era of the James Webb Space Telescope and the new ground-based, adaptive-optics-enabled giant telescopes, by obtaining these high precision measurements on key objects that Gaia could not reach, a mission that focuses on high precision astrometry science can consolidate our theoretical understanding of the local Universe, enable extrapolation of physical processes to remote redshifts, and derive a much more consistent picture of cosmological evolution and the likely fate of our cosmos. Already several missions have been proposed to address the science case of faint objects in motion using high precision astrometry missions: NEAT proposed for the ESA M3 opportunity, micro-NEAT for the S1 opportunity, and Theia for the M4 and M5 opportunities. Additional new mission configurations adapted with technological innovations could be envisioned to pursue accurate measurements of these extremely small motions. The goal of this White Paper is to address the fundamental science questions that are at stake when we focus on the motions of faint sky objects and to briefly review instrumentation and mission profiles.
|
|
| 9. |
- Scolnic, Dan, et al.
(författare)
-
The Pantheon+ analysis : the full data set and light-curve release
- 2022
-
Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
-
Tidskriftsartikel (refereegranskat)abstract
- Here we present 1701 light curves of 1550 unique, spectroscopically confirmed Type Ia supernovae (SNe Ia) that will be used to infer cosmological parameters as part of the Pantheon+ SN analysis and the Supernovae and H0 for the Equation of State of dark energy distance-ladder analysis. This effort is one part of a series of works that perform an extensive review of redshifts, peculiar velocities, photometric calibration, and intrinsic-scatter models of SNe Ia. The total number of light curves, which are compiled across 18 different surveys, is a significant increase from the first Pantheon analysis (1048 SNe), particularly at low redshift (z). Furthermore, unlike in the Pantheon analysis, we include light curves for SNe with z < 0.01 such that SN systematic covariance can be included in a joint measurement of the Hubble constant (H0) and the dark energy equation-of-state parameter (w). We use the large sample to compare properties of 151 SNe Ia observed by multiple surveys and 12 pairs/triplets of “SN siblings”—SNe found in the same host galaxy. Distance measurements, application of bias corrections, and inference of cosmological parameters are discussed in the companion paper by Brout et al., and the determination of H0 is discussed by Riess et al. These analyses will measure w with ∼3% precision and H0 with ∼1 km s−1 Mpc−1 precision.
|
|
| 10. |
- Tinyanont, Samaporn, et al.
(författare)
-
Supernova 2020wnt : An Atypical Superluminous Supernova with a Hidden Central Engine
- 2023
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 951:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present observations of a peculiar hydrogen- and helium-poor stripped-envelope (SE) supernova (SN) 2020wnt, primarily in the optical and near-infrared (near-IR). Its peak absolute bolometric magnitude of −20.9 mag (Lbol, peak = (6.8 ± 0.3) × 1043 erg s−1) and a rise time of 69 days are reminiscent of hydrogen-poor superluminous SNe (SLSNe I), luminous transients potentially powered by spinning-down magnetars. Before the main peak, there is a brief peak lasting <10 days post explosion, likely caused by interaction with circumstellar medium (CSM) ejected ∼years before the SN explosion. The optical spectra near peak lack a hot continuum and O ii absorptions, which are signs of heating from a central engine; they quantitatively resemble those of radioactivity-powered hydrogen/helium-poor Type Ic SESNe. At ∼1 yr after peak, nebular spectra reveal a blue pseudo-continuum and narrow O i recombination lines associated with magnetar heating. Radio observations rule out strong CSM interactions as the dominant energy source at +266 days post peak. Near-IR observations at +200–300 days reveal carbon monoxide and dust formation, which causes a dramatic optical light-curve dip. Pair-instability explosion models predict slow light curve and spectral features incompatible with observations. SN 2020wnt is best explained as a magnetar-powered core-collapse explosion of a 28 M⊙ pre-SN star. The explosion kinetic energy is significantly larger than the magnetar energy at peak, effectively concealing the magnetar-heated inner ejecta until well after peak. SN 2020wnt falls into a continuum between normal SNe Ic and SLSNe I, and demonstrates that optical spectra at peak alone cannot rule out the presence of a central engine.
|
|
