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

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

Reconstruction of hadronic decay products of tau leptons with the ATLAS experiment

This paper presents a new method of reconstructing the individual charged and neutral hadrons in tau decays with the ATLAS detector. The reconstructed hadrons are used to classify the decay mode and to calculate the visible four-momentum of reconstructed tau candidates, significantly improving the resolution with respect to the calibration in the existing tau reconstruction. The performance of the reconstruction algorithm is optimised and evaluated using simulation and validated using samples of Z→ττ and Z(→μμ)+jets events selected from proton–proton collisions at a centre-of-mass energy √s=8TeV, corresponding to an integrated luminosity of 5 fb−1.- We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF and DNSRC, Denmark; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, HGF, and MPG, Germany; GSRT, Greece; RGC, Hong Kong SAR, China; ISF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW and NCN, Poland; FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZS, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TAEK, Turkey; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, the Canada Council, CANARIE, CRC, Compute Canada, FQRNT, and the Ontario Innovation Trust, Canada; EPLANET, ERC, FP7, Horizon 2020 and Marie Sklodowska-Curie Actions, European Union; Investissements d'Avenir Labex and Idex, ANR, Region Auvergne and Fondation Partager le Savoir, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF; BSF, GIF and Minerva, Israel; BRF, Norway; the Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in th

Search for anomalous couplings in the W tb vertex from the measurement of double differential angular decay rates of single top quarks produced in the t-channel with the ATLAS detector

The electroweak production and subsequent decay of single top quarks is determined by the properties of the Wtb vertex. This vertex can be described by the complex parameters of an effective Lagrangian. An analysis of angular distributions of the decay products of single top quarks produced in the t -channel constrains these parameters simultaneously. The analysis described in this paper uses 4.6 fb−1 of proton-proton collision data at √s =7 TeV collected with the ATLAS detector at the LHC. Two parameters are measured simultaneously in this analysis. The fraction f 1 of decays containing transversely polarised W bosons is measured to be 0.37 ± 0.07 (stat.⊕syst.). The phase δ − between amplitudes for transversely and longitudinally polarised W bosons recoiling against left-handed b-quarks is measured to be −0.014π ± 0.036π (stat.⊕syst.). The correlation in the measurement of these parameters is 0.15. These values result in two-dimensional limits at the 95% confidence level on the ratio of the complex coupling parameters g R and V L, yielding Re[g R /V L] ∈ [−0.36, 0.10] and Im[g R /V L] ∈ [−0.17, 0.23] with a correlation of 0.11. The results are in good agreement with the predictions of the Standard Model

Searches for Higgs boson pair production in the hh→bbττ, γγWW∗, γγbb, bbbb channels with the ATLAS detector

Searches for both resonant and nonresonant Higgs boson pair production are performed in the hh→bbττ, γγWW∗ final states using 20.3  fb−1 of pp collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No evidence of their production is observed and 95% confidence-level upper limits on the production cross sections are set. These results are then combined with the published results of the hh→γγbb, bbbb analyses. An upper limit of 0.69 (0.47) pb on the nonresonant hh production is observed (expected), corresponding to 70 (48) times the SM gg→hh cross section. For production via narrow resonances, cross-section limits of hh production from a heavy Higgs boson decay are set as a function of the heavy Higgs boson mass. The observed (expected) limits range from 2.1 (1.1) pb at 260 GeV to 0.011 (0.018) pb at 1000 GeV. These results are interpreted in the context of two simplified scenarios of the Minimal Supersymmetric Standard Model

Search for the electroweak production of supersymmetric particles in sqrt(s)=8 TeV pp collisions with the ATLAS detector

The ATLAS experiment has performed extensive searches for the electroweak production of charginos, neutralinos, and staus. This article summarizes and extends the search for electroweak supersymmetry with new analyses targeting scenarios not covered by previously published searches. New searches use vectorboson fusion production, initial-state radiation jets, and low-momentum lepton final states, as well as multivariate analysis techniques to improve the sensitivity to scenarios with small mass splittings and low-production cross sections. Results are based on 20 fb−1 of proton-proton collision data at √s = 8 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. The new and existing searches are combined and interpreted in terms of 95% confidence-level exclusion limits in simplified models, where a single production process and decay mode is assumed, as well as within phenomenological supersymmetric models

Accuracy versus precision in boosted top tagging with the ATLAS detector

Abstract The identification of top quark decays where the top quark has a large momentum transverse to the beam axis, known as top tagging, is a crucial component in many measurements of Standard Model processes and searches for beyond the Standard Model physics at the Large Hadron Collider. Machine learning techniques have improved the performance of top tagging algorithms, but the size of the systematic uncertainties for all proposed algorithms has not been systematically studied. This paper presents the performance of several machine learning based top tagging algorithms on a dataset constructed from simulated proton-proton collision events measured with the ATLAS detector at √ s = 13 TeV. The systematic uncertainties associated with these algorithms are estimated through an approximate procedure that is not meant to be used in a physics analysis, but is appropriate for the level of precision required for this study. The most performant algorithms are found to have the largest uncertainties, motivating the development of methods to reduce these uncertainties without compromising performance. To enable such efforts in the wider scientific community, the datasets used in this paper are made publicly available.</jats:p

Observation of Long-Range Elliptic Azimuthal Anisotropies in root s=13 and 2.76 TeV pp Collisions with the ATLAS Detector

ATLAS has measured two-particle correlations as a function of the relative azimuthal angle, Δϕ, and pseudorapidity, Δη, in sqrt[s]=13 and 2.76 TeV pp collisions at the LHC using charged particles measured in the pseudorapidity interval |η|<2.5. The correlation functions evaluated in different intervals of measured charged-particle multiplicity show a multiplicity-dependent enhancement at Δϕ∼0 that extends over a wide range of Δη, which has been referred to as the "ridge." Per-trigger-particle yields, Y(Δϕ), are measured over 2<|Δη|<5. For both collision energies, the Y(Δϕ) distribution in all multiplicity intervals is found to be consistent with a linear combination of the per-trigger-particle yields measured in collisions with less than 20 reconstructed tracks, and a constant combinatoric contribution modulated by cos(2Δϕ). The fitted Fourier coefficient, v_{2,2}, exhibits factorization, suggesting that the ridge results from per-event cos(2ϕ) modulation of the single-particle distribution with Fourier coefficients v_{2}. The v_{2} values are presented as a function of multiplicity and transverse momentum. They are found to be approximately constant as a function of multiplicity and to have a p_{T} dependence similar to that measured in p+Pb and Pb+Pb collisions. The v_{2} values in the 13 and 2.76 TeV data are consistent within uncertainties. These results suggest that the ridge in pp collisions arises from the same or similar underlying physics as observed in p+Pb collisions, and that the dynamics responsible for the ridge has no strong sqrt[s] dependence

Measurement of the transverse momentum and ϕ∗ηϕη∗ distributions of Drell–Yan lepton pairs in proton–proton collisions at s√=8s=8 TeV with the ATLAS detector

Distributions of transverse momentum p T and the related angular variable φ∗ η of Drell–Yan lepton pairs are measured in 20.3 fb−1 of proton–proton collisions at √s = 8 TeV with the ATLAS detector at the LHC. Measurements in electron-pair and muon-pair final states are corrected for detector effects and combined. Compared to previous measurements in proton–proton collisions at √s = 7 TeV, these new measurements benefit from a larger data sample and improved control of systematic uncertainties. Measurements are performed in bins of lepton-pair mass above, around and below the Z-boson mass peak. The data are compared to predictions from perturbative and resummed QCD calculations. For values of φ∗ η < 1 the predictions from the Monte Carlo generator ResBos are generally consistent with the data within the theoretical uncertainties. However, at larger values of φ∗ η this is not the case. Monte Carlo generators based on the parton-shower approach are unable to describe the data over the full range of p T while the fixed-order prediction of Dynnlo falls below the data at high values of p T . ResBos and the parton-shower Monte Carlo generators provide a much better description of the evolution of the φ∗ η and p T distributions as a function of lepton-pair mass and rapidity than the basic shape of the data. Conte

Combination of searches for WW, WZ, and ZZ resonances in pp collisions at root s=8 TeV with the ATLAS detector

The ATLAS experiment at the CERN Large Hadron Collider has performed searches for new, heavy bosons decaying to WW, WZ and ZZ final states in multiple decay channels using 20.3 fb-1 of pp collision data at s=8 TeV. In the current study, the results of these searches are combined to provide a more stringent test of models predicting heavy resonances with couplings to vector bosons. Direct searches for a charged diboson resonance decaying to WZ in the ℓνℓ'ℓ' (ℓ=μ, e), ℓℓqq-, ℓνqq- and fully hadronic final states are combined and upper limits on the rate of production times branching ratio to the WZ bosons are compared with predictions of an extended gauge model with a heavy W' boson. In addition, direct searches for a neutral diboson resonance decaying to WW and ZZ in the ℓℓqq-, ℓνqq-, and fully hadronic final states are combined and upper limits on the rate of production times branching ratio to the WW and ZZ bosons are compared with predictions for a heavy, spin-2 graviton in an extended Randall-Sundrum model where the Standard Model fields are allowed to propagate in the bulk of the extra dimension