Heterogeneous network embedding enabling accurate disease association predictions.

BackgroundIt is significant to identificate complex biological mechanisms of various diseases in biomedical research. Recently, the growing generation of tremendous amount of data in genomics, epigenomics, metagenomics, proteomics, metabolomics, nutriomics, etc., has resulted in the rise of systematic biological means of exploring complex diseases. However, the disparity between the production of the multiple data and our capability of analyzing data has been broaden gradually. Furthermore, we observe that networks can represent many of the above-mentioned data, and founded on the vector representations learned by network embedding methods, entities which are in close proximity but at present do not actually possess direct links are very likely to be related, therefore they are promising candidate subjects for biological investigation.ResultsWe incorporate six public biological databases to construct a heterogeneous biological network containing three categories of entities (i.e., genes, diseases, miRNAs) and multiple types of edges (i.e., the known relationships). To tackle the inherent heterogeneity, we develop a heterogeneous network embedding model for mapping the network into a low dimensional vector space in which the relationships between entities are preserved well. And in order to assess the effectiveness of our method, we conduct gene-disease as well as miRNA-disease associations predictions, results of which show the superiority of our novel method over several state-of-the-arts. Furthermore, many associations predicted by our method are verified in the latest real-world dataset.ConclusionsWe propose a novel heterogeneous network embedding method which can adequately take advantage of the abundant contextual information and structures of heterogeneous network. Moreover, we illustrate the performance of the proposed method on directing studies in biology, which can assist in identifying new hypotheses in biological investigation

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Density functional calculations of nanoscale conductance

Density functional calculations for the electronic conductance of single molecules are now common. We examine the methodology from a rigorous point of view, discussing where it can be expected to work, and where it should fail. When molecules are weakly coupled to leads, local and gradient-corrected approximations fail, as the Kohn-Sham levels are misaligned. In the weak bias regime, XC corrections to the current are missed by the standard methodology. For finite bias, a new methodology for performing calculations can be rigorously derived using an extension of time-dependent current density functional theory from the Schroedinger equation to a Master equation.Comment: topical review, 28 pages, updated version with some revision

An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays

An amplitude analysis of the $\pi^{0}\pi^{0}$ system produced in radiative $J/\psi$ decays is presented. In particular, a piecewise function that describes the dynamics of the $\pi^{0}\pi^{0}$ system is determined as a function of $M_{\pi^{0}\pi^{0}}$ from an analysis of the $(1.311\pm0.011)\times10^{9}$ $J/\psi$ decays collected by the BESIII detector. The goal of this analysis is to provide a description of the scalar and tensor components of the $\pi^0\pi^0$ system while making minimal assumptions about the properties or number of poles in the amplitude. Such a model-independent description allows one to integrate these results with other related results from complementary reactions in the development of phenomenological models, which can then be used to directly fit experimental data to obtain parameters of interest. The branching fraction of $J/\psi \to \gamma \pi^{0}\pi^{0}$ is determined to be $(1.15\pm0.05)\times10^{-3}$, where the uncertainty is systematic only and the statistical uncertainty is negligible.Comment: Submitted to Phys. Rev. D 19 pages, 4 figure

Measurement of azimuthal asymmetries in inclusive charged dipion production in e+e−e^+e^- annihilations at s\sqrt{s} = 3.65 GeV

We present a measurement of the azimuthal asymmetries of two charged pions in the inclusive process $e^+e^-\rightarrow \pi\pi X$ based on a data set of 62 $\rm{pb}^{-1}$ at the center-of-mass energy $\sqrt{s}=3.65$ GeV collected with the BESIII detector. These asymmetries can be attributed to the Collins fragmentation function. We observe a nonzero asymmetry, which increases with increasing pion momentum. As our energy scale is close to that of the existing semi-inclusive deep inelastic scattering experimental data, the measured asymmetries are important inputs for the global analysis of extracting the quark transversity distribution inside the nucleon and are valuable to explore the energy evolution of the spin-dependent fragmentation function.Comment: 7 pages, 5 figure

Confirmation of a charged charmoniumlike state Zc(3885)∓Z_c(3885)^{\mp} in e+e−→π±(DDˉ∗)∓e^+e^-\to\pi^{\pm}(D\bar{D}^*)^\mp with double DD tag

We present a study of the process $e^+e^-\to\pi^{\pm}(D\bar{D}^*)^{\mp}$ using data samples of 1092~pb$^{-1}$ at $\sqrt{s}=4.23$~GeV and 826~pb$^{-1}$ at $\sqrt{s}=4.26$~GeV collected with the BESIII detector at the BEPCII storage ring. With full reconstruction of the $D$ meson pair and the bachelor $\pi^{\pm}$ in the final state, we confirm the existence of the charged structure $Z_c(3885)^{\mp}$ in the $(D\bar{D}^*)^{\mp}$ system in the two isospin processes $e^+e^-\to\pi^+D^0D^{*-}$ and $e^+e^-\to\pi^+D^-D^{*0}$. By performing a simultaneous fit, the statistical significance of $Zc(3885)^{\mp}$ signal is determined to be greater than 10$\sigma$, and its pole mass and width are measured to be $M_{\rm{pole}}$=(3881.7$\pm$1.6(stat.)$\pm$1.6(syst.))~MeV/$c^2$ and $\Gamma_{\rm{pole}}$=(26.6$\pm$2.0(stat.)$\pm$2.1(syst.))~MeV, respectively. The Born cross section times the $(D\bar{D}^*)^{\mp}$ branching fraction ($\sigma(e^+e^-\to\pi^{\pm}Z_{c}(3885)^{\mp}) \times Br(Z_{c}(3885)^{\mp}\to(D\bar{D}^*)^{\mp})$) is measured to be $(141.6\pm7.9(\text{stat.})\pm12.3(\text{syst.}))~\text{pb}$ at $\sqrt{s}=4.23$~GeV and $(108.4\pm6.9(\text{stat.})\pm8.8(\text{syst.}))~\text{pb}$ at $\sqrt{s}=4.26$~GeV. The polar angular distribution of the $\pi^{\pm}$-$Z_c(3885)^{\mp}$ system is consistent with the expectation of a quantum number assignment of $J^P=1^+$ for $Z_c(3885)^{\mp}$

Measurement of the e+e−→π+π−\mathrm e^+\mathrm e^-\rightarrow\mathrm\pi^+\mathrm\pi^- Cross Section between 600 and 900 MeV Using Initial State Radiation

We extract the $e^+e^-\rightarrow \pi^+\pi^-$ cross section in the energy range between 600 and 900 MeV, exploiting the method of initial state radiation. A data set with an integrated luminosity of 2.93 fb$^{-1}$ taken at a center-of-mass energy of 3.773 GeV with the BESIII detector at the BEPCII collider is used. The cross section is measured with a systematic uncertainty of 0.9%. We extract the pion form factor $|F_\pi|^2$ as well as the contribution of the measured cross section to the leading order hadronic vacuum polarization contribution to $(g-2)_\mu$. We find this value to be $a_\mu^{\pi\pi,\rm LO}(600-900\;\rm MeV) = (368.2 \pm 2.5_{\rm stat} \pm 3.3_{\rm sys})\cdot 10^{-10}$.Comment: 14 pages, 7 figures, accepted by PL

Observation of ηc→ωω\eta_c\to\omega\omega in J/ψ→γωωJ/\psi\to\gamma\omega\omega

Using a sample of $(1310.6\pm7.0)\times10^6$ $J/\psi$ events recorded with the BESIII detector at the symmetric electron positron collider BEPCII, we report the observation of the decay of the $(1^1 S_0)$ charmonium state $\eta_c$ into a pair of $\omega$ mesons in the process $J/\psi\to\gamma\omega\omega$. The branching fraction is measured for the first time to be $\mathcal{B}(\eta_c\to\omega\omega)= (2.88\pm0.10\pm0.46\pm0.68)\times10^{-3}$, where the first uncertainty is statistical, the second systematic and the third is from the uncertainty of $\mathcal{B}(J/\psi\to\gamma\eta_c)$. The mass and width of the $\eta_c$ are determined as $M=(2985.9\pm0.7\pm2.1)\,$MeV/$c^2$ and $\Gamma=(33.8\pm1.6\pm4.1)\,$MeV.Comment: 13 pages, 6 figure

Measurement of the proton form factor by studying e+e−→ppˉe^{+} e^{-}\rightarrow p\bar{p}

Using data samples collected with the BESIII detector at the BEPCII collider, we measure the Born cross section of $e^{+}e^{-}\rightarrow p\bar{p}$ at 12 center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective electromagnetic form factor of the proton is deduced under the assumption that the electric and magnetic form factors are equal $(|G_{E}|= |G_{M}|)$. In addition, the ratio of electric to magnetic form factors, $|G_{E}/G_{M}|$, and $|G_{M}|$ are extracted by fitting the polar angle distribution of the proton for the data samples with larger statistics, namely at $\sqrt{s}=$ 2232.4 and 2400.0 MeV and a combined sample at $\sqrt{s}$ = 3050.0, 3060.0 and 3080.0 MeV, respectively. The measured cross sections are in agreement with recent results from BaBar, improving the overall uncertainty by about 30\%. The $|G_{E}/G_{M}|$ ratios are close to unity and consistent with BaBar results in the same $q^{2}$ region, which indicates the data are consistent with the assumption that $|G_{E}|=|G_{M}|$ within uncertainties.Comment: 13 pages, 24 figure