Statistical method on nonrandom clustering with application to somatic mutations in cancer

<p>Abstract</p> <p>Background</p> <p>Human cancer is caused by the accumulation of tumor-specific mutations in oncogenes and tumor suppressors that confer a selective growth advantage to cells. As a consequence of genomic instability and high levels of proliferation, many passenger mutations that do not contribute to the cancer phenotype arise alongside mutations that drive oncogenesis. While several approaches have been developed to separate driver mutations from passengers, few approaches can specifically identify activating driver mutations in oncogenes, which are more amenable for pharmacological intervention.</p> <p>Results</p> <p>We propose a new statistical method for detecting activating mutations in cancer by identifying nonrandom clusters of amino acid mutations in protein sequences. A probability model is derived using order statistics assuming that the location of amino acid mutations on a protein follows a uniform distribution. Our statistical measure is the differences between pair-wise order statistics, which is equivalent to the size of an amino acid mutation cluster, and the probabilities are derived from exact and approximate distributions of the statistical measure. Using data in the Catalog of Somatic Mutations in Cancer (COSMIC) database, we have demonstrated that our method detects well-known clusters of activating mutations in KRAS, BRAF, PI3K, and <it>β</it>-catenin. The method can also identify new cancer targets as well as gain-of-function mutations in tumor suppressors.</p> <p>Conclusions</p> <p>Our proposed method is useful to discover activating driver mutations in cancer by identifying nonrandom clusters of somatic amino acid mutations in protein sequences.</p

Searches for the Zγ decay mode of the Higgs boson and for new high-mass resonances in pp collisions at √s=13 TeV with the ATLAS detector

This article presents searches for the Zγ decay of the Higgs boson and for narrow high-mass resonances decaying to Zγ, exploiting Z boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb−1 of pp collisions at √s=13 recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected — assuming Standard Model pp → H → Zγ production and decay) upper limit on the production cross section times the branching ratio for pp → H → Zγ is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level

Measurement of the Higgs boson coupling properties in the H → ZZ* → 4 decay channel at √s = 13 TeV with the ATLAS detector

The coupling properties of the Higgs boson are studied in the four-lepton (e, μ) decay channel using 36.1 fb−1 of pp collision data from the LHC at a centre-of-mass energy of 13 TeV collected by the ATLAS detector. Cross sections are measured for the main production modes in several exclusive regions of the Higgs boson production phase space and are interpreted in terms of coupling modifiers. The inclusive cross section times branching ratio for H → ZZ∗ decay and for a Higgs boson absolute rapidity below 2.5 is measured to be 1. 73 − 0.23 + 0.24 (stat.) − 0.08 + 0.10 (exp.) ± 0.04(th.) pb compared to the Standard Model prediction of 1.34±0.09 pb. In addition, the tensor structure of the Higgs boson couplings is studied using an effective Lagrangian approach for the description of interactions beyond the Standard Model. Constraints are placed on the non-Standard-Model CP-even and CP-odd couplings to Z bosons and on the CP-odd coupling to gluons

On generalized semi-Pareto and semi-Burr distributions and random coefficient minification processes

Burr distribution, Burr processes, Characterizations, Pareto distribution, Semi-Pareto distribution, Semi-Pareto processes,