Profound effect of profiling platform and normalization strategy on detection of differentially expressed microRNAs

Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of differential miRNA expression detection as well as (iii) increase inter-platform concordance. Results showed the successful adoption of loessM and generalized procrustes analysis to one-color miRNA profiling experiments

Embedding, compression and fiberwise homotopy theory

Given Poincare spaces M and X, we study the possibility of compressing embeddings of M x I in X x I down to embeddings of M in X. This results in a new approach to embedding in the metastable range both in the smooth and Poincare duality categories.Comment: Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol2/agt-2-15.abs.htm

The power spectrum of galaxies in the 2dF 100k redshift survey

We compute the real-space power spectrum and the redshift-space distortions of galaxies in the 2dF 100k galaxy redshift survey using pseudo-Karhunen-Loeve eigenmodes and the stochastic bias formalism. Our results agree well with those published by the 2dFGRS team, and have the added advantage of producing easy-to-interpret uncorrelated minimum-variance measurements of the galaxy-galaxy, galaxy-velocity and velocity-velocity power spectra in 27 k-bands, with narrow and well-behaved window functions in the range 0.01h/Mpc < k < 0.8h/Mpc. We find no significant detection of baryonic wiggles, although our results are consistent with a standard flat Omega_Lambda=0.7 ``concordance'' model and previous tantalizing hints of baryonic oscillations. We measure the galaxy-matter correlation coefficient r > 0.4 and the redshift-distortion parameter beta=0.49+/-0.16 for r=1 (beta=0.47+/- 0.16 without finger-of-god compression). Since this is an apparent-magnitude limited sample, luminosity-dependent bias may cause a slight red-tilt in the power spectum. A battery of systematic error tests indicate that the survey is not only impressive in size, but also unusually clean, free of systematic errors at the level to which our tests are sensitive. Our measurements and window functions are available at http://www.hep.upenn.edu/~max/2df.html together with the survey mask, radial selection function and uniform subsample of the survey that we have constructed.Comment: Replaced to match accepted MNRAS version, with new radial/angular systematics plot and sigma8 typo corrected. High-res figures, power spectra, windows and our uniform galaxy subsample with mask at http://www.hep.upenn.edu/~max/2df.html or from [email protected]. 26 journal pages, 28 fig

Numerical and Theoretical Study of a Monodisperse Hard-Sphere Glass Former

There exists a variety of theories of the glass transition and many more numerical models. But because the models need built-in complexity to prevent crystallization, comparisons with theory can be difficult. We study the dynamics of a deeply supersaturated \emph{monodisperse} four-dimensional (4D) hard-sphere fluid, which has no such complexity, but whose strong intrinsic geometrical frustration inhibits crystallization, even when deeply supersaturated. As an application, we compare its behavior to the mode-coupling theory (MCT) of glass formation. We find MCT to describe this system better than any other structural glass formers in lower dimensions. The reduction in dynamical heterogeneity in 4D suggested by a milder violation of the Stokes-Einstein relation could explain the agreement. These results are consistent with a mean-field scenario of the glass transition.Comment: 5 pages, 3 figure

Analytical Models for the Energetics of Cosmic Accretion Shocks, their Cosmological Evolution, and the Effect of Environment

We present an analytical description of the energetics of the population of cosmic accretion shocks, for a concordance cosmology. We calculate how the shock-processed accretion power and mass current are distributed among different shock Mach numbers, and how they evolve with cosmic time. We calculate the cumulative energy input of cosmic accretion shocks of any Mach number to the intergalactic medium as a function of redshift, and we compare it with the energy output of supernova explosions as well as with the energy input required to reionize the universe. In addition, we investigate and quantify the effect of environmental factors, such as local clustering properties and filament preheating on the statistical properties of these shocks. We find that the energy processed by accretion shocks is higher than the supernova energy output for z<3 and that it becomes more than an order of magnitude higher in the local universe. The energy processed by accretion shocks alone becomes comparable to the energy required to reionize the universe by z~3.5. Finally, we establish both qualitative and quantitatively that both local clustering as well as filament compression and preheating are important factors in determining the statistical properties of the cosmic accretion shock population.Comment: 13 pages, 5 figures, emulateap