Mixture SNPs effect on phenotype in genome-wide association studies

© 2015 Wang et al.; licensee BioMed Central. Background: Recently mixed linear models are used to address the issue of "missing" heritability in traditional Genome-wide association studies (GWAS). The models assume that all single-nucleotide polymorphisms (SNPs) are associated with the phenotypes of interest. However, it is more common that only a small proportion of SNPs have significant effects on the phenotypes, while most SNPs have no or very small effects. To incorporate this feature, we propose an efficient Hierarchical Bayesian Model (HBM) that extends the existing mixed models to enforce automatic selection of significant SNPs. The HBM models the SNP effects using a mixture distribution of a point mass at zero and a normal distribution, where the point mass corresponds to those non-associative SNPs. Results: We estimate the HBM using Gibbs sampling. The estimation performance of our method is first demonstrated through two simulation studies. We make the simulation setups realistic by using parameters fitted on the Framingham Heart Study (FHS) data. The simulation studies show that our method can accurately estimate the proportion of SNPs associated with the simulated phenotype and identify these SNPs, as well as adapt to certain model mis-specification than the standard mixed models. In addition, we analyze data from the FHS and the Health and Retirement Study (HRS) to study the association between Body Mass Index (BMI) and SNPs on Chromosome 16, and replicate the identified genetic associations. The analysis of the FHS data identifies 0.3% SNPs on Chromosome 16 that affect BMI, including rs9939609 and rs9939973 on the FTO gene. These two SNPs are in strong linkage disequilibrium with rs1558902 (Rsq =0.901 for rs9939609 and Rsq =0.905 for rs9939973), which has been reported to be linked with obesity in previous GWAS. We then replicate the findings using the HRS data: the analysis finds 0.4% of SNPs associated with BMI on Chromosome 16. Furthermore, around 25% of the genes that are identified to be associated with BMI are common between the two studies. Conclusions: The results demonstrate that the HBM and the associated estimation algorithm offer a powerful tool for identifying significant genetic associations with phenotypes of interest, among a large number of SNPs that are common in modern genetics studies.published_or_final_versio

GG: A domain involved in phage LTF apparatus and implicated in human MEB and non-syndromic hearing loss diseases

AbstractHere, we report the identification of a novel domain – GG (domain in KIAA1199, FAM3, POMGnT1 and Tmem2 proteins, with two well-conserved glycine residues), present in eukaryotic FAM3 superfamily (FAM3A, FAM3B, FAM3C and FAM3D), POMGnT1 (protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase), TEM2 proteins as well as phage gp35 proteins. GG domain has been revealed to be implicated in muscle–eye–brain disease and non-syndromic hearing loss. The presence of GG domain in Bacteriophage gp35 hinge connector of long tail fiber might reflect the horizontal gene transfer from organisms. And we proposed that GG domain might function as important structural element in phage LTF

High Performance Metasurface Antennas

Recently, metasurfaces (MSs) have received tremendous attention because their electromagnetic properties can be controlled at will. Generally, metasurface with hyperbolic phase distributions, namely, focusing metasurface, can be used to design high-gain antennas. Besides, metasurface has the ability of controlling the polarization state of electromagnetic wave. In this chapter, we first propose a new ultrathin broadband reflected MS and take it into application for high-gain planar antenna. Then, we propose multilayer multifunctional transmitted MSs to simultaneously enhance the gain and transform the linear polarization to circular polarization of the patch antenna. This kind of high-gain antenna eliminates the feed-block effect of the reflected ones

Direct detection of dark photon dark matter using radio telescopes

Dark photons can be the ultralight dark matter candidate, interacting with Standard Model particles via kinetic mixing. We propose to search for ultralight dark photon dark matter (DPDM) through the local absorption at different radio telescopes. The local DPDM can induce harmonic oscillations of electrons inside the antenna of radio telescopes. It leads to a monochromatic radio signal and can be recorded by telescope receivers. Using the observation data from the FAST telescope, the upper limit on the kinetic mixing can already reach $10^{-12}$ for DPDM oscillation frequencies at $1-1.5$ GHz, which is stronger than the cosmic microwave background constraint by about one order of magnitude. Furthermore, large-scale interferometric arrays like LOFAR and SKA1 telescopes can achieve extraordinary sensitivities for direct DPDM search from 10 MHz to 10 GHz.Comment: 5 pages, 3 figures + appendix. Match the accepted version (PRL

Capillary-Induced Ge Uniformly Distributed in N-Doped Carbon Nanotubes with Enhanced Li-Storage Performance

Germanium (Ge) is a prospective anode material for lithium-ion batteries, as it possesses large theoretical capacity, outstanding lithium-ion diffusivity, and excellent electrical conductivity. Ge suffers from drastic capacity decay and poor rate performance, however, owing to its low electrical conductivity and huge volume expansion during cycling processes. Herein, a novel strategy has been developed to synthesize a Ge at N-doped carbon nanotubes (Ge at N-CNTs) composite with Ge nanoparticles uniformly distributed in the N-CNTs by using capillary action. This unique structure could effectively buffer large volume expansion. When evaluated as an anode material, the Ge at N-CNTs demonstrate enhanced cycling stability and excellent rate capabilities

An Evidence Fusion Method with Importance Discounting Factors based on Neutrosophic Probability Analysis in DSmT Framework

To obtain effective fusion results of multi source evidences with different importance, an evidence fusion method with importance discounting factors based on neutrosopic probability analysis in DSmT framework is proposed. First, the reasonable evidence sources are selected out based on the statistical analysis of the pignistic probability functions of single focal elements. Secondly, the neutrosophic probability analysis is conducted based on the similarities of the pignistic probability functions from the prior evidence knowledge of the reasonable evidence sources. Thirdly, the importance discounting factors of the reasonable evidence sources are obtained based on the neutrosophic probability analysis and the reliability discounting factors of the real-time evidences are calculated based on probabilistic-based distances. Fourthly, the real-time evidences are discounted by the importance discounting factors and then the evidences with the mass assignments of neutrosophic empty sets are discounted by the reliability discounting factors. Finally, DSmT+PCR5 of importance discounted evidences is applied. Experimental examples show that the decision results based on the proposed fusion method are different from the results based on the existed fusion methods. Simulation experiments of recognition fusion are performed and the superiority of proposed method is testified well by the simulation results

MTA3-SOX2 Module Regulates Cancer Stemness and Contributes to Clinical Outcomes of Tongue Carcinoma.

Cancer cell plasticity plays critical roles in both tumorigenesis and tumor progression. Metastasis-associated protein 3 (MTA3), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex and multi-effect coregulator, can serve as a tumor suppressor in many cancer types. However, the role of MTA3 in tongue squamous cell cancer (TSCC) remains unclear although it is the most prevalent head and neck cancer and often with poor prognosis. By analyzing both published datasets and clinical specimens, we found that the level of MTA3 was lower in TSCC compared to normal tongue tissues. Data from gene set enrichment analysis (GSEA) also indicated that MTA3 was inversely correlated with cancer stemness. In addition, the levels of MTA3 in both samples from TSCC patients and TSCC cell lines were negatively correlated with SOX2, a key regulator of the plasticity of cancer stem cells (CSCs). We also found that SOX2 played an indispensable role in MTA3-mediated CSC repression. Using the mouse model mimicking human TSCC we demonstrated that the levels of MTA3 and SOX2 decreased and increased, respectively, during the process of tumorigenesis and progression. Finally, we showed that the patients in the MTA

MTA3-SOX2 Module Regulates Cancer Stemness and Contributes to Clinical Outcomes of Tongue Carcinoma

Cancer cell plasticity plays critical roles in both tumorigenesis and tumor progression. Metastasis-associated protein 3 (MTA3), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex and multi-effect coregulator, can serve as a tumor suppressor in many cancer types. However, the role of MTA3 in tongue squamous cell cancer (TSCC) remains unclear although it is the most prevalent head and neck cancer and often with poor prognosis. By analyzing both published datasets and clinical specimens, we found that the level of MTA3 was lower in TSCC compared to normal tongue tissues. Data from gene set enrichment analysis (GSEA) also indicated that MTA3 was inversely correlated with cancer stemness. In addition, the levels of MTA3 in both samples from TSCC patients and TSCC cell lines were negatively correlated with SOX2, a key regulator of the plasticity of cancer stem cells (CSCs). We also found that SOX2 played an indispensable role in MTA3-mediated CSC repression. Using the mouse model mimicking human TSCC we demonstrated that the levels of MTA3 and SOX2 decreased and increased, respectively, during the process of tumorigenesis and progression. Finally, we showed that the patients in the MTA