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

Search for Gravitational-lensing Signatures in the Full Third Observing Run of the LIGO–Virgo Network

Abstract Gravitational lensing by massive objects along the line of sight to the source causes distortions to gravitational wave (GW) signals; such distortions may reveal information about fundamental physics, cosmology, and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO-Virgo network. We search for repeated signals from strong lensing by (1) performing targeted searches for subthreshold signals, (2) calculating the degree of overlap among the intrinsic parameters and sky location of pairs of signals, (3) comparing the similarities of the spectrograms among pairs of signals, and (4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by (1) frequency-independent phase shifts in strongly lensed images, and (2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the nondetection of GW lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects.</jats:p

Search for Gravitational-lensing Signatures in the Full Third Observing Run of the LIGO–Virgo Network

Abstract Gravitational lensing by massive objects along the line of sight to the source causes distortions to gravitational wave (GW) signals; such distortions may reveal information about fundamental physics, cosmology, and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO-Virgo network. We search for repeated signals from strong lensing by (1) performing targeted searches for subthreshold signals, (2) calculating the degree of overlap among the intrinsic parameters and sky location of pairs of signals, (3) comparing the similarities of the spectrograms among pairs of signals, and (4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by (1) frequency-independent phase shifts in strongly lensed images, and (2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the nondetection of GW lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects.</jats:p

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

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

Abstract The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.</jats:p