Since I Fell in Love With You

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Dinucleotide controlled null models for comparative RNA gene prediction

<p>Abstract</p> <p>Background</p> <p>Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak <it>et al</it>. [BMC Bioinformatics. 8:33] that RNA gene prediction programs can be biased by the genomic dinucleotide content, in particular those programs using a thermodynamic folding model including stacking energies. As a consequence, there is need for dinucleotide-preserving control strategies to assess the significance of such predictions. While there have been randomization algorithms for single sequences for many years, the problem has remained challenging for multiple alignments and there is currently no algorithm available.</p> <p>Results</p> <p>We present a program called SISSIz that simulates multiple alignments of a given average dinucleotide content. Meeting additional requirements of an accurate null model, the randomized alignments are on average of the same sequence diversity and preserve local conservation and gap patterns. We make use of a phylogenetic substitution model that includes overlapping dependencies and site-specific rates. Using fast heuristics and a distance based approach, a tree is estimated under this model which is used to guide the simulations. The new algorithm is tested on vertebrate genomic alignments and the effect on RNA structure predictions is studied. In addition, we directly combined the new null model with the RNAalifold consensus folding algorithm giving a new variant of a thermodynamic structure based RNA gene finding program that is not biased by the dinucleotide content.</p> <p>Conclusion</p> <p>SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require randomization of multiple alignments can be considered.</p> <p>Availability</p> <p>SISSIz is available as open source C code that can be compiled for every major platform and downloaded here: <url>http://sourceforge.net/projects/sissiz</url>.</p

New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis

Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide

A Galerkin method for retarded boundary integral equations with smooth and compactly supported temporal basis functions

We consider retarded boundary integral formulations of the three-dimensional wave equation in unbounded domains. Our goal is to apply a Galerkin method in space and time in order to solve these problems numerically. In this approach the computation of the system matrix entries is the major bottleneck. We will propose new types of finite-dimensional spaces for the time discretization. They allow variable time-stepping, variable order of approximation and simplify the quadrature problem arising in the generation of the system matrix substantially. The reason is that the basis functions of these spaces are globally smooth and compactly supported. In order to perform numerical tests concerning our new basis functions we consider the special case that the boundary of the scattering problem is the unit sphere. In this case explicit solutions of the problem are available which will serve as reference solutions for the numerical experiments

Reduced basis approximation and a posteriori error estimation for affinely parametrized elliptic coercive partial differential equations

In this paper we consider (hierarchical, Lagrange) reduced basis approximation and a posteriori error estimation for linear functional outputs of affinely parametrized elliptic coercive partial differential equations. The essential ingredients are (primal-dual) Galerkin projection onto a low-dimensional space associated with a smooth "parametric manifold"-dimension reduction; efficient and effective greedy sampling methods for identification of optimal and numerically stable approximations-rapid convergence; a posteriori error estimation procedures-rigorous and sharp bounds for the linear-functional outputs of interest; and Offline-Online computational decomposition strategies-minimum marginal cost for high performance in the real-time/embedded (e.g., parameter-estimation, control) and many-query (e.g., design optimization, multi-model/scale) contexts. We present illustrative results for heat conduction and convection-diffusion, inviscid flow, and linear elasticity; outputs include transport rates, added mass, and stress intensity factors