Improved Covariance Model Parameter Estimation Using RNA Thermodynamic Properties

Covariance models are a powerful description of non-coding RNA (ncRNA) families that can be used to search nucleotide databases for new members of these ncRNA families. Currently, estimation of the parameters of a covariance model (state transition and emission scores) is based only on the observed frequencies of mutations, insertions, and deletions in known ncRNA sequences. For families with very few known members, this can result in rather uninformative models where the consensus sequence has a good score and most deviations from consensus have a fairly uniform poor score. It is proposed here to combine the traditional observed-frequency information with known information about free energy changes in RNA helix formation and loop length changes. More thermodynamically probable deviations from the consensus sequence will then be favored in database search. The thermodynamic information may be incorporated into the models as informative priors that depend on neighboring consensus nucleotides and on loop lengths

Universal distribution of threshold forces at the depinning transition

We study the distribution of threshold forces at the depinning transition for an elastic system of finite size, driven by an external force in a disordered medium at zero temperature. Using the functional renormalization group (FRG) technique, we compute the distribution of pinning forces in the quasi-static limit. This distribution is universal up to two parameters, the average critical force, and its width. We discuss possible definitions for threshold forces in finite-size samples. We show how our results compare to the distribution of the latter computed recently within a numerical simulation of the so-called critical configuration.Comment: 12 pages, 7 figures, revtex

Ebbie: automated analysis and storage of small RNA cloning data using a dynamic web server

BACKGROUND: DNA sequencing is used ubiquitously: from deciphering genomes[1] to determining the primary sequence of small RNAs (smRNAs) [2-5]. The cloning of smRNAs is currently the most conventional method to determine the actual sequence of these important regulators of gene expression. Typical smRNA cloning projects involve the sequencing of hundreds to thousands of smRNA clones that are delimited at their 5' and 3' ends by fixed sequence regions. These primers result from the biochemical protocol used to isolate and convert the smRNA into clonable PCR products. Recently we completed a smRNA cloning project involving tobacco plants, where analysis was required for ~700 smRNA sequences[6]. Finding no easily accessible research tool to enter and analyze smRNA sequences we developed Ebbie to assist us with our study. RESULTS: Ebbie is a semi-automated smRNA cloning data processing algorithm, which initially searches for any substring within a DNA sequencing text file, which is flanked by two constant strings. The substring, also termed smRNA or insert, is stored in a MySQL and BlastN database. These inserts are then compared using BlastN to locally installed databases allowing the rapid comparison of the insert to both the growing smRNA database and to other static sequence databases. Our laboratory used Ebbie to analyze scores of DNA sequencing data originating from an smRNA cloning project[6]. Through its built-in instant analysis of all inserts using BlastN, we were able to quickly identify 33 groups of smRNAs from ~700 database entries. This clustering allowed the easy identification of novel and highly expressed clusters of smRNAs. Ebbie is available under GNU GPL and currently implemented on CONCLUSION: Ebbie was designed for medium sized smRNA cloning projects with about 1,000 database entries [6-8].Ebbie can be used for any type of sequence analysis where two constant primer regions flank a sequence of interest. The reliable storage of inserts, and their annotation in a MySQL database, BlastN[9] comparison of new inserts to dynamic and static databases make it a powerful new tool in any laboratory using DNA sequencing. Ebbie also prevents manual mistakes during the excision process and speeds up annotation and data-entry. Once the server is installed locally, its access can be restricted to protect sensitive new DNA sequencing data. Ebbie was primarily designed for smRNA cloning projects, but can be applied to a variety of RNA and DNA cloning projects[2,3,10,11]

jViz.RNA 4.0—Visualizing Pseudoknots and RNA Editing Employing Compressed Tree Graphs

Previously, we have introduced an improved version of jViz.RNA which enabled faster and more stable RNA visualization by employing compressed tree graphs. However, the new RNA representation and visualization method required a sophisticated mechanism of pseudoknot visualization. In this work, we present our novel pseudoknot classification and implementation of pseudoknot visualization in the context of the new RNA graph model. We then compare our approach with other RNA visualization software, and demonstrate jViz.RNA 4.0’s benefits compared to other software. Additionally, we introduce interactive editing functionality into jViz.RNA and demonstrate its benefits in exploring and building RNA structures. The results presented highlight the new high degree of utility jViz.RNA 4.0 now offers. Users are now able to visualize pseudoknotted RNA, manipulate the resulting automatic layouts to suit their individual needs, and change both positioning and connectivity of the RNA molecules examined. Care was taken to limit overlap between structural elements, particularly in the case of pseudoknots to ensure an intuitive and informative layout of the final RNA structure

Measuring functional renormalization group fixed-point functions for pinned manifolds

Exact numerical minimization of interface energies is used to test the functional renormalization group (FRG) analysis for interfaces pinned by quenched disorder. The fixed-point function R(u) (the correlator of the coarse-grained disorder) is computed. In dimensions D=d+1, a linear cusp in R''(u) is confirmed for random bond (d=1,2,3), random field (d=0,2,3), and periodic (d=2,3) disorders. The functional shocks that lead to this cusp are seen. Small, but significant, deviations from 1-loop FRG results are compared to 2-loop corrections. The cross-correlation for two copies of disorder is compared with a recent FRG study of chaos.Comment: 4 pages, 4 figure

Super-rough phase of the random-phase sine-Gordon model: Two-loop results

We consider the two-dimensional random-phase sine-Gordon and study the vicinity of its glass transition temperature $T_c$, in an expansion in small $\tau=(T_c-T)/T_c$, where $T$ denotes the temperature. We derive renormalization group equations in cubic order in the anharmonicity, and show that they contain two universal invariants. Using them we obtain that the correlation function in the super-rough phase for temperature $T<T_c$ behaves at large distances as $\bar{} = \mathcal{A}\ln^2(|x|/a) + \mathcal{O}[\ln(|x|/a)]$, where the amplitude $\mathcal{A}$ is a universal function of temperature $\mathcal{A}=2\tau^2-2\tau^3+\mathcal{O}(\tau^4)$. This result differs at two-loop order, i.e., $\mathcal{O}(\tau^3)$, from the prediction based on results from the "nearly conformal" field theory of a related fermion model. We also obtain the correction-to-scaling exponent.Comment: 34 page

Functional renormalization group at large N for random manifolds

We introduce a method, based on an exact calculation of the effective action at large N, to bridge the gap between mean field theory and renormalization in complex systems. We apply it to a d-dimensional manifold in a random potential for large embedding space dimension N. This yields a functional renormalization group equation valid for any d, which contains both the O(epsilon=4-d) results of Balents-Fisher and some of the non-trivial results of the Mezard-Parisi solution thus shedding light on both. Corrections are computed at order O(1/N). Applications to the problems of KPZ, random field and mode coupling in glasses are mentioned

Wetting and Minimal Surfaces

We study minimal surfaces which arise in wetting and capillarity phenomena. Using conformal coordinates, we reduce the problem to a set of coupled boundary equations for the contact line of the fluid surface, and then derive simple diagrammatic rules to calculate the non-linear corrections to the Joanny-de Gennes energy. We argue that perturbation theory is quasi-local, i.e. that all geometric length scales of the fluid container decouple from the short-wavelength deformations of the contact line. This is illustrated by a calculation of the linearized interaction between contact lines on two opposite parallel walls. We present a simple algorithm to compute the minimal surface and its energy based on these ideas. We also point out the intriguing singularities that arise in the Legendre transformation from the pure Dirichlet to the mixed Dirichlet-Neumann problem.Comment: 22 page

Functional renormalization group for anisotropic depinning and relation to branching processes

Using the functional renormalization group, we study the depinning of elastic objects in presence of anisotropy. We explicitly demonstrate how the KPZ-term is always generated, even in the limit of vanishing velocity, except where excluded by symmetry. We compute the beta-function to one loop taking properly into account the non-analyticity. This gives rise to additional terms, missed in earlier studies. A crucial question is whether the non-renormalization of the KPZ-coupling found at 1-loop order extends beyond the leading one. Using a Cole-Hopf-transformed theory we argue that it is indeed uncorrected to all orders. The resulting flow-equations describe a variety of physical situations. A careful analysis of the flow yields several non-trivial fixed points. All these fixed points are transient since they possess one unstable direction towards a runaway flow, which leaves open the question of the upper critical dimension. The runaway flow is dominated by a Landau-ghost-mode. For SR elasticity, using the Cole-Hopf transformed theory we identify a non-trivial 3-dimensional subspace which is invariant to all orders and contains all above fixed points as well as the Landau-mode. It belongs to a class of theories which describe branching and reaction-diffusion processes, of which some have been mapped onto directed percolation.Comment: 20 pages, 30 figures, revtex