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

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Efeito da redução da proteína bruta e da suplementação de aminoácidos para suínos machos castrados, dos 70 aos 100kg

Estudou-se o efeito da redução da proteína bruta (PB) e da suplementação de aminoácidos em dietas para suínos, dos 70 aos 100kg. Foram utilizados 48 suínos machos, castrados, híbridos comerciais, com o peso inicial de 70,12±1,56kg, distribuídos em delineamento experimental de blocos ao acaso, com quatro níveis de proteína bruta na dieta, 17,95; 16,45; 14,95; 13,45, seis repetições e dois animais por unidade experimental. Não foi observado efeito dos tratamentos sobre o ganho de peso diário e sobre o consumo de dieta diário. Houve efeito quadrático dos níveis de PB sobre a conversão alimentar, que melhorou até o nível estimado de 15,7% de proteína bruta. Não houve influência dos níveis de PB sobre a espessura de toucinho e sobre o rendimento de carne magra. Conclui-se que a redução da proteína bruta na dieta de até 4,5 pontos percentuais, com suplementação de aminoácidos, para suínos na fase de terminação, não influi no consumo de dieta diário, no ganho de peso diário e nas características de carcaça. Melhor conversão alimentar foi estimada para suínos alimentados com dietas contendo 15,7% de proteína bruta.</jats:p

Observation of the Y(4140)Y(4140) structure in the J/ψ ϕJ/\psi\,\phi Mass Spectrum in B±→J/ψ ϕKB^\pm\to J/\psi\,\phi K cays

The observation of the $Y(4140)$ structure in $B^\pm\rightarrow J/\psi\,\phi K^\pm$ decays produced in $\bar{p} p$ collisions at \sqrt{s}=1.96~\TeV is reported with a statistical significance greater than 5 standard deviations. A fit to the $J/\psi\,\phi$ mass spectrum is performed assuming the presence of a Breit-Wigner resonance. The fit yields a signal of $19^{+6}_{-5}$ resonance events, and resonance mass and width of 4143.4^{+2.9}_{-3.0}(\mathrm{stat})\pm0.6(\mathrm{syst})~\MeVcc and 15.3^{+10.4}_{-6.1}(\mathrm{stat})\pm2.5(\mathrm{syst})~\MeVcc respectively. The parameters of this resonance-like structure are consistent with values reported from an earlier CDF analysis.Comment: 7 pages, 2 figures, submited to Phys. Rev. Let

Search for Higgs bosons produced in association with b quarks

We present a search for neutral Higgs bosons decaying into bb̄, produced in association with b quarks in pp̄ collisions. This process could be observable in supersymmetric models with high values of tanβ. The event sample corresponds to 2.6fb -1 of integrated luminosity collected with the CDF II detector at the Fermilab Tevatron collider. We search for an enhancement in the mass of the two leading jets in events with three jets identified as coming from b quarks using a displaced vertex algorithm. A data-driven procedure is used to estimate the dijet mass spectrum of the nonresonant multijet background. The contributions of backgrounds and a possible Higgs boson signal are determined by a two-dimensional fit of the data, using the dijet mass together with an additional variable which is sensitive to the flavor composition of the three tagged jets. We set mass-dependent limits on σ(pp̄→)×B(→bb̄) which are applicable for a narrow scalar particle produced in association with b quarks. We also set limits on tanβ in supersymmetric Higgs models including the effects of the Higgs boson width. © 2012 American Physical Society

Measurement of the W+W- Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Dilepton Events

We present a measurement of the W+W- production cross section using 184/pb of ppbar collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W+W- -> l+l-vvbar, where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0+2.2-0.8 events. The resulting W+W- production cross section measurement of sigma(ppbar -> W+W-) = 14.6 +5.8 -5.1 (stat) +1.8 -3.0 (syst) +-0.9 (lum) pb agrees well with the Standard Model expectation.Comment: 8 pages, 2 figures, 2 tables. To be submitted to Physical Review Letter

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

Integrated Molecular Characterization of Testicular Germ Cell Tumors

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance—KIT, KRAS, and NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas. Shen et al. identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting