Contextualization of drug-mediator relations using evidence networks

Abstract Background Genomic analysis of drug response can provide unique insights into therapies that can be used to match the “right drug to the right patient.” However, the process of discovering such therapeutic insights using genomic data is not straightforward and represents an area of active investigation. EDDY (Evaluation of Differential DependencY), a statistical test to detect differential statistical dependencies, is one method that leverages genomic data to identify differential genetic dependencies. EDDY has been used in conjunction with the Cancer Therapeutics Response Portal (CTRP), a dataset with drug-response measurements for more than 400 small molecules, and RNAseq data of cell lines in the Cancer Cell Line Encyclopedia (CCLE) to find potential drug-mediator pairs. Mediators were identified as genes that showed significant change in genetic statistical dependencies within annotated pathways between drug sensitive and drug non-sensitive cell lines, and the results are presented as a public web-portal (EDDY-CTRP). However, the interpretability of drug-mediator pairs currently hinders further exploration of these potentially valuable results. Methods In this study, we address this challenge by constructing evidence networks built with protein and drug interactions from the STITCH and STRING interaction databases. STITCH and STRING are sister databases that catalog known and predicted drug-protein interactions and protein-protein interactions, respectively. Using these two databases, we have developed a method to construct evidence networks to “explain” the relation between a drug and a mediator.  Results We applied this approach to drug-mediator relations discovered in EDDY-CTRP analysis and identified evidence networks for ~70% of drug-mediator pairs where most mediators were not known direct targets for the drug. Constructed evidence networks enable researchers to contextualize the drug-mediator pair with current research and knowledge. Using evidence networks, we were able to improve the interpretability of the EDDY-CTRP results by linking the drugs and mediators with genes associated with both the drug and the mediator. Conclusion We anticipate that these evidence networks will help inform EDDY-CTRP results and enhance the generation of important insights to drug sensitivity that will lead to improved precision medicine applications

Search for Scalar Diphoton Resonances in the Mass Range 65−60065-600 GeV with the ATLAS Detector in pppp Collision Data at s\sqrt{s} = 8 TeVTeV

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65–600 GeV is performed using $20.3\text{}\text{}{\mathrm{fb}}^{-1}$ of $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$ $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95% confidence level on the production cross section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches

Search for Higgs and ZZ Boson Decays to J/ψγJ/\psi\gamma and Υ(nS)γ\Upsilon(nS)\gamma with the ATLAS Detector

A search for the decays of the Higgs and $Z$ bosons to $J/\psi\gamma$ and $\Upsilon(nS)\gamma$ ($n=1,2,3$) is performed with $pp$ collision data samples corresponding to integrated luminosities of up to $20.3\mathrm{fb}^{-1}$ collected at $\sqrt{s}=8\mathrm{TeV}$ with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% CL upper limits are placed on the branching fractions. In the $J/\psi\gamma$ final state the limits are $1.5\times10^{-3}$ and $2.6\times10^{-6}$ for the Higgs and $Z$ bosons, respectively, while in the $\Upsilon(1S,2S,3S)\,\gamma$ final states the limits are $(1.3,1.9,1.3)\times10^{-3}$ and $(3.4,6.5,5.4)\times10^{-6}$, respectively

Finska tingsdomares bedömningar av partsutlåtanden givna på plats i rätten eller via videokonferens

Professionals within the judicial system sometimes believe they can assess whether someone is lying or not based on cues such as body language and emotional expression. Research has, however, shown that this is impossible. The Finnish Supreme Court has also given rulings in accordance with this demonstrated fact. There has also been previous research on whether party or witness statements are assessed differently in court depending on whether they are given live, via videoconference, or via prerecorded video. In the present study, we investigated how a Finnish sample of district judges (N=47) assigned probative value to different variables concerning the statement or the statement giver, such as body language and emotional expression. We also investigated the connection between the judges’ beliefs about the relevance of body language and emotional expression and their preference for live statements or statements via videoconference. The judges reported assigning equal amounts of probative value to statements given live and statements given via videoconference. However, judges found it easier to detect deception live, and this preference correlated with how relevant they thought body language is when assessing the probative value of the statement. In other words, a slight bias to assess live statements more favorably than statements given via videoconference might still exist. More effort needs to be put into making judges and Supreme Courts aware of robust scientific results that have been the subject of decades of research, such as the fact that one cannot assess whether someone is lying or not based on cues such as body language

Search for Scalar-Charm pair production in pp collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

The results of a dedicated search for pair production of scalar partners of charm quarks are reported. The search is based on an integrated luminosity of 20.3 fb$^{-1}$ of pp collisions at $\sqrt{s}=8$ TeV recorded with the ATLAS detector at the LHC. The search is performed using events with large missing transverse momentum and at least two jets, where the two leading jets are each tagged as originating from c-quarks. Events containing isolated electrons or muons are vetoed. In an R-parity-conserving minimal supersymmetric scenario in which a single scalar-charm state is kinematically accessible, and where it decays exclusively into a charm quark and a neutralino, 95% confidence-level upper limits are obtained in the scalar-charm-neutralino mass plane such that, for neutralino masses below 200 GeV, scalar-charm masses up to 490 GeV are excluded

Search for Higgs and Z Boson Decays to J/ψγJ/\psi\gamma and Υ(nS)γ\Upsilon(nS)\gamma with the ATLAS Detector

A search for the decays of the Higgs and Z bosons to J/ψγ and ϒ(nS)γ (n=1,2,3) is performed with pp collision data samples corresponding to integrated luminosities of up to 20.3 fb-1 collected at s=8 TeV with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% C.L. upper limits are placed on the branching fractions. In the J/ψγ final state the limits are 1.5×10-3 and 2.6×10-6 for the Higgs and Z boson decays, respectively, while in the ϒ(1S,2S,3S)γ final states the limits are (1.3,1.9,1.3)×10-3 and (3.4,6.5,5.4)×10-6, respectively

Measurement of differential J/ψJ/\psi production cross-sections and forward-backward ratio in p+Pb collisions with the ATLAS detector

Measurements of differential cross-sections for $J/\psi$ production in p+Pb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV at the LHC with the ATLAS detector are presented. The data set used corresponds to an integrated luminosity of 28.1 nb$^{-1}$. The $J/\psi$ mesons are reconstructed in the dimuon decay channel over the transverse momentum range $8<p_{\mathrm{T}}<30$ GeV and over the center-of-mass rapidity range $-2.87<y^{*}<1.94$. Prompt $J/\psi$ are separated from $J/\psi$ resulting from $b$-hadron decays through an analysis of the distance between the $J/\psi$ decay vertex and the event primary vertex. The differential cross-section for production of nonprompt $J/\psi$ is compared to a FONLL calculation that does not include nuclear effects. Forward-backward production ratios are presented and compared to theoretical predictions. These results constrain the kinematic dependence of nuclear modifications of charmonium and $b$-quark production in p+Pb collisions