Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). 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 promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Model-based Cross-correlation Search for Gravitational Waves from the Low-mass X-Ray Binary Scorpius X-1 in LIGO O3 Data

We present the results of a model-based search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1 using LIGO detector data from the third observing run of Advanced LIGO and Advanced Virgo. This is a semicoherent search that uses details of the signal model to coherently combine data separated by less than a specified coherence time, which can be adjusted to balance sensitivity with computing cost. The search covered a range of gravitational-wave frequencies from 25 to 1600 Hz, as well as ranges in orbital speed, frequency, and phase determined from observational constraints. No significant detection candidates were found, and upper limits were set as a function of frequency. The most stringent limits, between 100 and 200 Hz, correspond to an amplitude h0 of about 10−25 when marginalized isotropically over the unknown inclination angle of the neutron star's rotation axis, or less than 4 × 10−26 assuming the optimal orientation. The sensitivity of this search is now probing amplitudes predicted by models of torque balance equilibrium. For the usual conservative model assuming accretion at the surface of the neutron star, our isotropically marginalized upper limits are close to the predicted amplitude from about 70 to 100 Hz; the limits assuming that the neutron star spin is aligned with the most likely orbital angular momentum are below the conservative torque balance predictions from 40 to 200 Hz. Assuming a broader range of accretion models, our direct limits on gravitational-wave amplitude delve into the relevant parameter space over a wide range of frequencies, to 500 Hz or more

Searches for Gravitational Waves from Known Pulsars at Two Harmonics in the Second and Third LIGO-Virgo Observing Runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h (0) for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q (22) and ellipticities epsilon. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437-4715 and J0711-6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of similar to 100 and similar to 20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C (21) and C (22). For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory

Searches for gravitational waves from known pulsars at two harmonics in the second and third LIGO-Virgo observing runs

We present a targeted search for continuous gravitational waves (GWs) from 236 pulsars using data from the third observing run of LIGO and Virgo (O3) combined with data from the second observing run (O2). Searches were for emission from the l = m = 2 mass quadrupole mode with a frequency at only twice the pulsar rotation frequency (single harmonic) and the l = 2, m = 1, 2 modes with a frequency of both once and twice the rotation frequency (dual harmonic). No evidence of GWs was found, so we present 95% credible upper limits on the strain amplitudes h0 for the single-harmonic search along with limits on the pulsars' mass quadrupole moments Q22 and ellipticities ε. Of the pulsars studied, 23 have strain amplitudes that are lower than the limits calculated from their electromagnetically measured spin-down rates. These pulsars include the millisecond pulsars J0437−4715 and J0711−6830, which have spin-down ratios of 0.87 and 0.57, respectively. For nine pulsars, their spin-down limits have been surpassed for the first time. For the Crab and Vela pulsars, our limits are factors of ∼100 and ∼20 more constraining than their spin-down limits, respectively. For the dual-harmonic searches, new limits are placed on the strain amplitudes C21 and C22. For 23 pulsars, we also present limits on the emission amplitude assuming dipole radiation as predicted by Brans-Dicke theory

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO’s and Advanced Virgo’s Third Observing Run

International audienceWe report on a search for compact binary coalescences where at least one binary component has a mass between 0.2  M⊙ and 1.0  M⊙ in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14  yr-1. This implies an upper limit on the merger rate of subsolar binaries in the range [220−24200]  Gpc-3 yr-1, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2  M⊙<mPBH<1.0  M⊙ is fPBH≡ΩPBH/ΩDM≲6%. This improves existing constraints on primordial black hole abundance by a factor of ∼3. The other is a dissipative dark matter model, in which fermionic dark matter can collapse and form black holes. The upper limit on the fraction of dark matter black holes depends on the minimum mass of the black holes that can be formed: the most constraining result is obtained at Mmin=1  M⊙, where fDBH≡ΩDBH/ΩDM≲0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses

Search for gravitational waves from Scorpius X-1 with a hidden Markov model in O3 LIGO data

Results are presented for a semi-coherent search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1, using a hidden Markov model (HMM) to allow for spin wandering. This search improves on previous HMM-based searches of Laser Interferometer Gravitational-wave Observatory (LIGO) data by including the orbital period in the search template grid, and by analyzing data from the latest (third) observing run (O3). In the frequency range searched, from 60 to 500 Hz, we find no evidence of gravitational radiation. This is the most sensitive search for Scorpius X-1 using a HMM to date. For the most sensitive sub-band, starting at $256.06$Hz, we report an upper limit on gravitational wave strain (at $95 \%$ confidence) of $h_{0}^{95\%}=6.16\times10^{-26}$, assuming the orbital inclination angle takes its electromagnetically restricted value $\iota=44^{\circ}$. The upper limits on gravitational wave strain reported here are on average a factor of $\sim 3$ lower than in the O2 HMM search. This is the first Scorpius X-1 HMM search with upper limits that reach below the indirect torque-balance limit for certain sub-bands, assuming $\iota=44^{\circ}$

Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO-Virgo data

International audienceWe present a directed search for continuous gravitational wave (CW) signals emitted by spinningneutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presenceof a numerous population of neutron stars has been reported in the literature, turning this region into a veryinteresting place to look for CWs. In this search, data from the full O3 LIGO-Virgo run in the detectorfrequency band [10, 2000] Hz have been used. No significant detection was found and 95% confidencelevel upper limits on the signal strain amplitude were computed, over the full search band, with the deepestlimit of about $7.6 \times 10^{-26}$ at ≃142 Hz. These results are significantly more constraining than those reportedin previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity andr-mode amplitude. These limits can be also translated into constraints in the black hole mass–boson massplane for a hypothetical population of boson clouds around spinning black holes located in the GC

All-sky, all-frequency directional search for persistent gravitational waves from Advanced LIGO’s and Advanced Virgo’s first three observing runs

We present the first results from an all-sky all-frequency (ASAF) search for an anisotropic stochastic gravitational-wave background using the data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. Upper limit maps on broadband anisotropies of a persistent stochastic background were published for all observing runs of the LIGO-Virgo detectors. However, a broadband analysis is likely to miss narrowband signals as the signal-to-noise ratio of a narrowband signal can be significantly reduced when combined with detector output from other frequencies. Data folding and the computationally efficient analysis pipeline, PyStoch, enable us to perform the radiometer map-making at every frequency bin. We perform the search at 3072 HEALPix equal area pixels uniformly tiling the sky and in every frequency bin of width 1-32 Hz in the range 20-1726 Hz, except for bins that are likely to contain instrumental artefacts and hence are notched. We do not find any statistically significant evidence for the existence of narrowband gravitational-wave signals in the analyzed frequency bins. Therefore, we place 95\% confidence upper limits on the gravitational-wave strain for each pixel-frequency pair, the limits are in the range (0.030 - 9.6) \times10^{-24}. In addition, we outline a method to identify candidate pixel-frequency pairs that could be followed up by a more sensitive (and potentially computationally expensive) search, e.g., a matched-filtering-based analysis, to look for fainter nearly monochromatic coherent signals. The ASAF analysis is inherently independent of models describing any spectral or spatial distribution of power. We demonstrate that the ASAF results can be appropriately combined over frequencies and sky directions to successfully recover the broadband directional and isotropic results