Bayesian meta-analysis for identifying periodically expressed genes in fission yeast cell cycle

The effort to identify genes with periodic expression during the cell cycle from genome-wide microarray time series data has been ongoing for a decade. However, the lack of rigorous modeling of periodic expression as well as the lack of a comprehensive model for integrating information across genes and experiments has impaired the effort for the accurate identification of periodically expressed genes. To address the problem, we introduce a Bayesian model to integrate multiple independent microarray data sets from three recent genome-wide cell cycle studies on fission yeast. A hierarchical model was used for data integration. In order to facilitate an efficient Monte Carlo sampling from the joint posterior distribution, we develop a novel Metropolis--Hastings group move. A surprising finding from our integrated analysis is that more than 40% of the genes in fission yeast are significantly periodically expressed, greatly enhancing the reported 10--15% of the genes in the current literature. It calls for a reconsideration of the periodically expressed gene detection problem.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS300 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Fermat Potentials for Non-Perturbative Gravitational Lensing

The images of many distant galaxies are displaced, distorted and often multiplied by the presence of foreground massive galaxies near the line of sight; the foreground galaxies act as gravitational lenses. Commonly, the lens equation, which relates the placement and distortion of the images to the real source position in the thin-lens scenario, is obtained by extremizing the time of arrival among all the null paths from the source to the observer (Fermat's principle). We show that the construction of envelopes of certain families of null surfaces consitutes an alternative variational principle or version of Fermat's principle that leads naturally to a lens equation in a generic spacetime with any given metric. We illustrate the construction by deriving the lens equation for static asymptotically flat thin lens spacetimes. As an application of the approach, we find the bending angle for moving thin lenses in terms of the bending angle for the same deflector at rest. Finally we apply this construction to cosmological spacetimes (FRW) by using the fact they are all conformally related to Minkowski space.Comment: accepted for publication in Phys. Rev.

Dynamics of Fermat potentials in non-perturbative gravitational lensing

We present a framework, based on the null-surface formulation of general relativity, for discussing the dynamics of Fermat potentials for gravitational lensing in a generic situation without approximations of any kind. Additionally, we derive two lens equations: one for the case of thick compact lenses and the other one for lensing by gravitational waves. These equations in principle generalize the astrophysical scheme for lensing by removing the thin-lens approximation while retaining the weak fields.Comment: Accepted for publication in Phys. Rev.

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl

Iterative Approach to Gravitational Lensing Theory

We develop an iterative approach to gravitational lensing theory based on approximate solutions of the null geodesic equations. The approach can be employed in any space-time which is ``close'' to a space-time in which the null geodesic equations can be completely integrated, such as Minkowski space-time, Robertson-Walker cosmologies, or Schwarzschild-Kerr geometries. To illustrate the method, we construct the iterative gravitational lens equations and time of arrival equation for a single Schwarzschild lens. This example motivates a discussion of the relationship between the iterative approach, the standard thin lens formulation, and an exact formulation of gravitational lensing.Comment: 27 pages, 2 figures, submitted to Phys.Rev.D, minor revisions, new reference

Cosmic Microwave Background anisotropies from second order gravitational perturbations

This paper presents a complete analysis of the effects of second order gravitational perturbations on Cosmic Microwave Background anisotropies, taking explicitly into account scalar, vector and tensor modes. We also consider the second order perturbations of the metric itself obtaining them, for a universe dominated by a collision-less fluid, in the Poisson gauge, by transforming the known results in the synchronous gauge. We discuss the resulting second order anisotropies in the Poisson gauge, and analyse the possible relevance of the different terms. We expect that, in the simplest scenarios for structure formation, the main effect comes from the gravitational lensing by scalar perturbations, that is known to give a few percent contribution to the anisotropies at small angular scales.Comment: 15 pages, revtex, no figures. Version to be published in Phys. Rev.

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies

Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of haematological cancers

Evolution of Second-Order Cosmological Perturbations and Non-Gaussianity

We present a second-order gauge-invariant formalism to study the evolution of curvature perturbations in a Friedmann-Robertson-Walker universe filled by multiple interacting fluids. We apply such a general formalism to describe the evolution of the second-order curvature perturbations in the standard one-single field inflation, in the curvaton and in the inhomogeneous reheating scenarios for the generation of the cosmological perturbations. Moreover, we provide the exact expression for the second-order temperature anisotropies on large scales, including second-order gravitational effects and extend the well-known formula for the Sachs-Wolfe effect at linear order. Our findings clarify what is the exact non-linearity parameter f_NL entering in the determination of higher-order statistics such as the bispectrum of Cosmic Microwave Background temperature anisotropies. Finally, we compute the level of non-Gaussianity in each scenario for the creation of cosmological perturbations.Comment: 14 pages, LaTeX file. Further comments adde