Evaluation of pre-processing on the meta-analysis of DNA methylation data from the Illumina HumanMethylation450 BeadChip platform

Introduction Meta-analysis is a powerful means for leveraging the hundreds of experiments being run worldwide into more statistically powerful analyses. This is also true for the analysis of omic data, including genome-wide DNA methylation. In particular, thousands of DNA methylation profiles generated using the Illumina 450k are stored in the publicly accessible Gene Expression Omnibus (GEO) repository. Often, however, the intensity values produced by the BeadChip (raw data) are not deposited, therefore only pre-processed values -obtained after computational manipulation- are available. Pre-processing is possibly different among studies and may then affect meta-analysis by introducing non-biological sources of variability. Material and methods To systematically investigate the effect of pre-processing on meta-analysis, we analysed four different collections of DNA methylation samples (datasets), each composed of two subsets, for which raw data from controls (i.e. healthy subjects) and cases (i.e. patients) are available. We pre-processed the data from each dataset with nine among the most common pipelines found in literature. Moreover, we evaluated the performance of regRCPqn, a modification of the RCP algorithm that aims to improve data consistency. For each combination of pre-processing (9 7 9), we first evaluated the between-sample variability among control subjects and, then, we identified genomic positions that are differentially methylated between cases and controls (differential analysis). Results and conclusion The pre-processing of DNA methylation data affects both the between-sample variability and the loci identified as differentially methylated, and the effects of pre-processing are strongly dataset-dependent. By contrast, application of our renormalization algorithm regRCPqn: (i) reduces variability and (ii) increases agreement between meta-analysed datasets, both critical components of data harmonization

Two-pion exchange potential and the πN\pi N amplitude

We discuss the two-pion exchange potential which emerges from a box diagram with one nucleon (the spectator) restricted to its mass shell, and the other nucleon line replaced by a subtracted, covariant $\pi N$ scattering amplitude which includes $\Delta$, Roper, and $D_{13}$ isobars, as well as contact terms and off-shell (non-pole) dressed nucleon terms. The $\pi N$ amplitude satisfies chiral symmetry constraints and fits $\pi N$ data below $\sim$ 700 MeV pion energy. We find that this TPE potential can be well approximated by the exchange of an effective sigma and delta meson, with parameters close to the ones used in one-boson-exchange models that fit $NN$ data below the pion production threshold.Comment: 9 pages (RevTex) and 7 postscript figures, in one uuencoded gzipped tar fil

Association of \u3ci\u3eEscherichia coli\u3c/i\u3e O157:H7 \u3ci\u3etir\u3c/i\u3e polymorphisms with human infection

Background: Emerging molecular, animal model and epidemiologic evidence suggests that Shigatoxigenic Escherichia coli O157:H7 (STEC O157) isolates vary in their capacity to cause human infection and disease. The translocated intimin receptor (tir) and intimin (eae) are virulence factors and bacterial receptor-ligand proteins responsible for tight STEC O157 adherence to intestinal epithelial cells. They represent logical genomic targets to investigate the role of sequence variation in STEC O157 pathogenesis and molecular epidemiology. The purposes of this study were (1) to identify tir and eae polymorphisms in diverse STEC O157 isolates derived from clinically ill humans and healthy cattle (the dominant zoonotic reservoir) and (2) to test any observed tir and eae polymorphisms for association with human (vs bovine) isolate source. Results: Five polymorphisms were identified in a 1,627-bp segment of tir. Alleles of two tir polymorphisms, tir 255 T\u3eA and repeat region 1-repeat unit 3 (RR1-RU3, presence or absence) had dissimilar distributions among human and bovine isolates. More than 99% of 108 human isolates possessed the tir 255 T\u3eA T allele and lacked RR1-RU3. In contrast, the tir 255 T\u3eA T allele and RR1-RU3 absence were found in 55% and 57%, respectively, of 77 bovine isolates. Both polymorphisms associated strongly with isolate source (p \u3c 0.0001), but not by pulsed field gel electrophoresis type or by stx1 and stx2 status (as determined by PCR). Two eae polymorphisms were identified in a 2,755-bp segment of 44 human and bovine isolates; 42 isolates had identical eae sequences. The eae polymorphisms did not associate with isolate source. Conclusion: Polymorphisms in tir but not eae predict the propensity of STEC O157 isolates to cause human clinical disease. The over-representation of the tir 255 T\u3eA T allele in human-derived isolates vs the tir 255 T\u3eA A allele suggests that these isolates have a higher propensity to cause disease. The high frequency of bovine isolates with the A allele suggests a possible bovine ecological niche for this STEC O157 subset

Combined Analysis of Near-Threshold Production of omega and phi Mesons in Nucleon-Nucleon Collisions within an Effective Meson-Nucleon Model

Vector meson ($V = \omega, \phi$) production in near-threshold elementary nucleon-nucleon collisions $pp\to ppV$, $pn\to pnV$ and $pn\to dV$ is studied within an effective meson-nucleon theory. It is shown that a set of effective parameters can be established to describe fairly well the available experimental data of angular distributions and the energy dependence of the total cross sections without explicit implementation of the Okubo-Zweig-Iisuka rule violation. Isospin effects are considered in detail and compared with experimental data whenever available

Di-electrons from η\eta meson Dalitz decay in proton-proton collisions

The reaction $pp \to pp \eta \to pp \gamma e^+ e^-$ is discussed within a covariant effective meson-nucleon theory. The model is adjusted to data of the subreaction $pp \to pp \eta$. Our focus is on di-electrons from Dalitz decays of $\eta$ mesons, $\eta\to \gamma \gamma^* \to\gamma e^+e^-$, and the role of the corresponding transition form factor $F_{\eta \gamma \gamma^*}$. Numerical results are presented for the intermediate energy kinematics of HADES experiments

Medium Modification of The Pion-Pion Interaction at Finite Density

We discuss medium modifications of the unitarized pion-pion interaction in the nuclear medium. We incorporate both the effects of chiral symmetry restoration and the influence of collective nuclear pionic modes originating from the p-wave coupling of the pion to delta-hole configurations. We show in particular that the dropping of the sigma meson mass significantly enhances the low energy structure created by the in-medium collective pionic modes.Comment: 26 pages, 7 figures included, Latex fil

The twin paradox and Mach's principle

The problem of absolute motion in the context of the twin paradox is discussed. It is shown that the various versions of the clock paradox feature some aspects which Mach might have been appreciated. However, the ultimate cause of the behavior of the clocks must be attributed to the autonomous status of spacetime, thereby proving the relational program advocated by Mach as impracticable.Comment: Latex2e, 11 pages, 6 figures, 33 references, no tables. Accepted for publication in The European Physical Journal PLUS (EPJ PLUS