An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Cell Specific eQTL Analysis without Sorting Cells

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Observation of electroweak production of Wγ with two jets in proton-proton collisions at √s = 13 TeV

A first observation is presented for the electroweak production of a W boson, a photon, and two jets in proton-proton collisions. The W boson decays are selected by requiring one identified electron or muon and an imbalance in transverse momentum. The two jets are required to have a high dijet mass and a large separation in pseudorapidity. The measurement is based on data collected with the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb$^{-1}$. The observed (expected) significance for this process is 4.9 (4.6) standard deviations. After combining with previously reported CMS results at 8 TeV, the observed (expected) significance is 5.3 (4.8) standard deviations. The cross section for the electroweak W$_{γjj}$ production in a restricted fiducial region is measured as 20.4 +/- 4.5 fb and the total cross section for W$_{γ}$ production in association with 2 jets in the same fiducial region is 108 +/- 16 fb. All results are in good agreement with recent theoretical predictions. Constraints are placed on anomalous quartic gauge couplings in terms of dimension-8 effective field theory operators

ϒ production in p–Pb collisions at √sNN=8.16 TeV

ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

The second-order Fourier coefficients (υ$_{2}$) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb$^{-1}$. The scalar product method is used to extract the υ$_{2}$ coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p$_{T}$ < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ$_{2}$ values for the Υ mesons are found to be consistent with zero

Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

Measurement of prompt D0^{0} and D‾\overline{D}0^{0} meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root SNN\sqrt{S_{NN}} = 5.02 TeV

The strong Coulomb field created in ultrarelativistic heavy ion collisions is expected to produce a rapiditydependent difference (Av2) in the second Fourier coefficient of the azimuthal distribution (elliptic flow, v2) between D0 (uc) and D0 (uc) mesons. Motivated by the search for evidence of this field, the CMS detector at the LHC is used to perform the first measurement of Av2. The rapidity-averaged value is found to be (Av2) = 0.001 ? 0.001 (stat)? 0.003 (syst) in PbPb collisions at ?sNN = 5.02 TeV. In addition, the influence of the collision geometry is explored by measuring the D0 and D0mesons v2 and triangular flow coefficient (v3) as functions of rapidity, transverse momentum (pT), and event centrality (a measure of the overlap of the two Pb nuclei). A clear centrality dependence of prompt D0 meson v2 values is observed, while the v3 is largely independent of centrality. These trends are consistent with expectations of flow driven by the initial-state geometry. ? 2021 The Author. Published by Elsevier B.V. This is an open access article under the CC BY licens

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p