How genetic risk contributes to autoimmune liver disease

Genome-wide association studies (GWAS) for autoimmune hepatitis (AIH) and GWAS/genome-wide meta-analyses (GWMA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) have been successful over the past decade, identifying about 100 susceptibility loci in the human genome, with strong associations with the HLA locus and many susceptibility variants outside the HLA locus with relatively low risk. However, identifying causative variants and genes and determining their effects on liver cells and their immunological microenvironment is far from trivial. Polygenic risk scores (PRSs) based on current genome-wide data have limited potential to predict individual disease risk. Interestingly, results of mediated expression score regression analysis provide evidence that a substantial portion of gene expression at susceptibility loci is mediated by genetic risk variants, in contrast to many other complex diseases. Genome- and transcriptome-wide comparisons between AIH, PBC, and PSC could help to better delineate the shared inherited component of autoimmune liver diseases (AILDs), and statistical fine-mapping, chromosome X-wide association testing, and genome-wide in silico drug screening approaches recently applied to GWMA data from PBC could potentially be successfully applied to AIH and PSC. Initial successes through single-cell RNA sequencing (scRNA-seq) experiments in PBC and PSC now raise high hopes for understanding the impact of genetic risk variants in the context of liver-resident immune cells and liver cell subpopulations, and for bridging the gap between genetics and disease

From Next-Generation Sequencing Alignments to Accurate Comparison and Validation of Single-Nucleotide Variants: The Pibase Software

Scientists working with single-nucleotide variants (SNVs), inferred by next-generation sequencing software, often need further information regarding true variants, artifacts and sequence coverage gaps. In clinical diagnostics, e.g. SNVs must usually be validated by visual inspection or several independent SNV-callers. We here demonstrate that 0.5–60% of relevant SNVs might not be detected due to coverage gaps, or might be misidentified. Even low error rates can overwhelm the true biological signal, especially in clinical diagnostics, in research comparing healthy with affected cells, in archaeogenetic dating or in forensics. For these reasons, we have developed a package called pibase, which is applicable to diploid and haploid genome, exome or targeted enrichment data. pibase extracts details on nucleotides from alignment files at user-specified coordinates and identifies reproducible genotypes, if present. In test cases pibase identifies genotypes at 99.98% specificity, 10-fold better than other tools. pibase also provides pair-wise comparisons between healthy and affected cells using nucleotide signals (10-fold more accurately than a genotype-based approach, as we show in our case study of monozygotic twins). This comparison tool also solves the problem of detecting allelic imbalance within heterozygous SNVs in copy number variation loci, or in heterogeneous tumor sequences

LTRharvest, an efficient and flexible software for de novo detection of LTR retrotransposons

<p>Abstract</p> <p>Background</p> <p>Transposable elements are abundant in eukaryotic genomes and it is believed that they have a significant impact on the evolution of gene and chromosome structure. While there are several completed eukaryotic genome projects, there are only few high quality genome wide annotations of transposable elements. Therefore, there is a considerable demand for computational identification of transposable elements. LTR retrotransposons, an important subclass of transposable elements, are well suited for computational identification, as they contain long terminal repeats (LTRs).</p> <p>Results</p> <p>We have developed a software tool <it>LTRharvest </it>for the <it>de novo </it>detection of full length LTR retrotransposons in large sequence sets. <it>LTRharvest </it>efficiently delivers high quality annotations based on known LTR transposon features like length, distance, and sequence motifs. A quality validation of <it>LTRharvest </it>against a gold standard annotation for <it>Saccharomyces cerevisae </it>and <it>Drosophila melanogaster </it>shows a sensitivity of up to 90% and 97% and specificity of 100% and 72%, respectively. This is comparable or slightly better than annotations for previous software tools. The main advantage of <it>LTRharvest </it>over previous tools is (a) its ability to efficiently handle large datasets from finished or unfinished genome projects, (b) its flexibility in incorporating known sequence features into the prediction, and (c) its availability as an open source software.</p> <p>Conclusion</p> <p><it>LTRharvest </it>is an efficient software tool delivering high quality annotation of LTR retrotransposons. It can, for example, process the largest human chromosome in approx. 8 minutes on a Linux PC with 4 GB of memory. Its flexibility and small space and run-time requirements makes <it>LTRharvest </it>a very competitive candidate for future LTR retrotransposon annotation projects. Moreover, the structured design and implementation and the availability as open source provides an excellent base for incorporating novel concepts to further improve prediction of LTR retrotransposons.</p

Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface

The nuclear polarization of $\mathrm{H}_2$ molecules formed by recombination of nuclear polarized H atoms on the surface of a storage cell initially coated with a silicon-based polymer has been measured by using the longitudinal double-spin asymmetry in deep-inelastic positron-proton scattering. The molecules are found to have a substantial nuclear polarization, which is evidence that initially polarized atoms retain their nuclear polarization when absorbed on this type of surfac

Seasonal Variations in Vegetation Indices derived from in situ Type Vegetation Monitoring System at typical landcovers in Japan : From the Observation Results in PGLIERC and Lake Biwa Project

研究概要:本研究では光学センサー搭載衛星データの検証及び地表面フラックスとの対応関係を調べるために簡易式の地上設置型植生モニタリングシステムを日本を代表する土地被覆上(草地,水田,アカマツ林,落葉広葉樹)に設置し,それぞれの土地被覆から得られる植生指標の季節変化について示した.その結果,以下の知見が得られた;1.草原系(草地・水田)では各植生の季節変化特性を良好にモニターすることが可能である,2.森林系(アカマツ林・落葉広葉樹)ではセンサーとキャノピーの距離が近すぎるため,思うような結果を得ることが出来なかった.3.ただし全般としては各土地被覆特性を示す連続したデータを取得することができ,システムの妥当性を示すことができた

Inclusive cross section and double helicity asymmetry for \pi^0 production in p+p collisions at sqrt(s)=200 GeV: Implications for the polarized gluon distribution in the proton

The PHENIX experiment presents results from the RHIC 2005 run with polarized proton collisions at sqrt(s)=200 GeV, for inclusive \pi^0 production at mid-rapidity. Unpolarized cross section results are given for transverse momenta p_T=0.5 to 20 GeV/c, extending the range of published data to both lower and higher p_T. The cross section is described well for p_T < 1 GeV/c by an exponential in p_T, and, for p_T > 2 GeV/c, by perturbative QCD. Double helicity asymmetries A_LL are presented based on a factor of five improvement in uncertainties as compared to previously published results, due to both an improved beam polarization of 50%, and to higher integrated luminosity. These measurements are sensitive to the gluon polarization in the proton, and exclude maximal values for the gluon polarization.Comment: 375 authors, 7 pages, 3 figures. Submitted to Phys. Rev. D, Rapid Communications. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Azimuthal anisotropy of pi^0 and eta mesons in Au+Au collisions at sqrt(s_NN)=200 GeV

The azimuthal anisotropy coefficients v_2 and v_4 of pi^0 and eta mesons are measured in Au+Au collisions at sqrt(s_NN)=200 GeV, as a function of transverse momentum p_T (1-14 GeV/c) and centrality. The extracted v_2 coefficients are found to be consistent between the two meson species over the measured p_T range. The ratio of v_4/v_2^2 for pi^0 mesons is found to be independent of p_T for 1-9 GeV/c, implying a lack of sensitivity of the ratio to the change of underlying physics with p_T. Furthermore, the ratio of v_4/v_2^2 is systematically larger in central collisions, which may reflect the combined effects of fluctuations in the initial collision geometry and finite viscosity in the evolving medium.Comment: 384 authors, 71 institutions, 11 pages, 9 figures, and 2 tables. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Centrality categorization for R_{p(d)+A} in high-energy collisions

High-energy proton- and deuteron-nucleus collisions provide an excellent tool for studying a wide array of physics effects, including modifications of parton distribution functions in nuclei, gluon saturation, and color neutralization and hadronization in a nuclear environment, among others. All of these effects are expected to have a significant dependence on the size of the nuclear target and the impact parameter of the collision, also known as the collision centrality. In this article, we detail a method for determining centrality classes in p(d)+A collisions via cuts on the multiplicity at backward rapidity (i.e., the nucleus-going direction) and for determining systematic uncertainties in this procedure. For d+Au collisions at sqrt(s_NN) = 200 GeV we find that the connection to geometry is confirmed by measuring the fraction of events in which a neutron from the deuteron does not interact with the nucleus. As an application, we consider the nuclear modification factors R_{p(d)+A}, for which there is a potential bias in the measured centrality dependent yields due to auto-correlations between the process of interest and the backward rapidity multiplicity. We determine the bias correction factor within this framework. This method is further tested using the HIJING Monte Carlo generator. We find that for d+Au collisions at sqrt(s_NN)=200 GeV, these bias corrections are small and vary by less than 5% (10%) up to p_T = 10 (20) GeV. In contrast, for p+Pb collisions at sqrt(s_NN) = 5.02 TeV we find these bias factors are an order of magnitude larger and strongly p_T dependent, likely due to the larger effect of multi-parton interactions.Comment: 375 authors, 18 pages, 16 figures, 4 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Medium modification of jet fragmentation in Au+Au collisions at sqrt(s_NN)=200 GeV measured in direct photon-hadron correlations

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at sqrt(s_NN)=200 GeV. The p_T of the photon is an excellent approximation to the initial p_T of the jet and the ratio z_T=p_T^h/p_T^\gamma is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p. I_ AA, the ratio of jet fragment yield in Au+Au to that in p+p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high z_T. The fragment yield at low z_T is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.Comment: 562 authors, 70 insitutions, 8 pages, and 3 figures. Submitted to Phys. Rev. Lett. v2 has minor changes to improve clarity. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm