A comprehensive evaluation of alignment algorithms in the context of RNA-seq.

Transcriptome sequencing (RNA-Seq) overcomes limitations of previously used RNA quantification methods and provides one experimental framework for both high-throughput characterization and quantification of transcripts at the nucleotide level. The first step and a major challenge in the analysis of such experiments is the mapping of sequencing reads to a transcriptomic origin including the identification of splicing events. In recent years, a large number of such mapping algorithms have been developed, all of which have in common that they require algorithms for aligning a vast number of reads to genomic or transcriptomic sequences. Although the FM-index based aligner Bowtie has become a de facto standard within mapping pipelines, a much larger number of possible alignment algorithms have been developed also including other variants of FM-index based aligners. Accordingly, developers and users of RNA-seq mapping pipelines have the choice among a large number of available alignment algorithms. To provide guidance in the choice of alignment algorithms for these purposes, we evaluated the performance of 14 widely used alignment programs from three different algorithmic classes: algorithms using either hashing of the reference transcriptome, hashing of reads, or a compressed FM-index representation of the genome. Here, special emphasis was placed on both precision and recall and the performance for different read lengths and numbers of mismatches and indels in a read. Our results clearly showed the significant reduction in memory footprint and runtime provided by FM-index based aligners at a precision and recall comparable to the best hash table based aligners. Furthermore, the recently developed Bowtie 2 alignment algorithm shows a remarkable tolerance to both sequencing errors and indels, thus, essentially making hash-based aligners obsolete

A Compact Approximate Solution to the Friedel-Anderson Impuriy Problem

An approximate groundstate of the Anderson-Friedel impurity problem is presented in a very compact form. It requires solely the optimization of two localized electron states and consists of four Slater states (Slater determinants). The resulting singlet ground state energy lies far below the Anderson mean field solution and agrees well with the numerical results by Gunnarsson and Schoenhammer, who used an extensive 1/N_{f}-expansion for a spin 1/2 impurity with double occupancy of the impurity level. PACS: 85.20.Hr, 72.15.R

Magnetic Field Effects on Quasiparticles in Strongly Correlated Local Systems

We show that quasiparticles in a magnetic field of arbitrary strength $H$ can be described by field dependent parameters. We illustrate this approach in the case of an Anderson impurity model and use the numerical renormalization group (NRG) to calculate the renormalized parameters for the levels with spin $\sigma$, $\tilde\epsilon_{\mathrm{d},\sigma}(H)$, resonance width $\tilde\Delta(H)$ and the effective local quasiparticle interaction $\tilde U(H)$. In the Kondo or strong correlation limit of the model the progressive de-renormalization of the quasiparticles can be followed as the magnetic field is increased. The low temperature behaviour, including the conductivity, in arbitrary magnetic field can be calculated in terms of the field dependent parameters using the renormalized perturbation expansion. Using the NRG the field dependence of the spectral density on higher scales is also calculated.Comment: 15 pages, 17 figure

Landauer-type transport theory for interacting quantum wires: Application to carbon nanotube Y junctions

We propose a Landauer-like theory for nonlinear transport in networks of one-dimensional interacting quantum wires (Luttinger liquids). A concrete example of current experimental focus is given by carbon nanotube Y junctions. Our theory has three basic ingredients that allow to explicitly solve this transport problem: (i) radiative boundary conditions to describe the coupling to external leads, (ii) the Kirchhoff node rule describing charge conservation, and (iii) density matching conditions at every node.Comment: final version, to be published in PR

Identifying the topology of protein complexes from affinity purification assays

Motivation: Recent advances in high-throughput technologies have made it possible to investigate not only individual protein interactions, but also the association of these proteins in complexes. So far the focus has been on the prediction of complexes as sets of proteins from the experimental results. The modular substructure and the physical interactions within the protein complexes have been mostly ignored

Melting properties of a simple tight-binding model of transition metals: I.The region of half-filled d-band

We present calculations of the free energy, and hence the melting properties, of a simple tight-binding model for transition metals in the region of d-band filling near the middle of a d-series, the parameters of the model being designed to mimic molybdenum. The melting properties are calculated for pressures ranging from ambient to several Mbar. The model is intended to be the simplest possible tight-binding representation of the two basic parts of the energy: first, the pairwise repulsion due to Fermi exclusion; and second, the d-band bonding energy described in terms of an electronic density of states that depends on structure. In addition to the number of d-electrons, the model contains four parameters, which are adjusted to fit the pressure dependent d-band width and the zero-temperature pressure-volume relation of Mo. We show that the resulting model reproduces well the phonon dispersion relations of Mo in the body-centred-cubic structure, as well as the radial distribution function of the high-temperature solid and liquid given by earlier first-principles simulations. Our free-energy calculations start from the free energy of the liquid and solid phases of the purely repulsive pair-potential model, without d-band bonding. The free energy of the full tight-binding model is obtained from this by thermodynamic integration. The resulting melting properties of the model are quite close to those given by earlier first-principles work on Mo. An interpretation of these melting properties is provided by showing how they are related to those of the purely repulsive model.Comment: 34 pages, 12 figures. Accepted for publication in Journal of Chemical Physic

Fermi Edge Singularities in the Mesoscopic Regime: II. Photo-absorption Spectra

We study Fermi edge singularities in photo-absorption spectra of generic mesoscopic systems such as quantum dots or nanoparticles. We predict deviations from macroscopic-metallic behavior and propose experimental setups for the observation of these effects. The theory is based on the model of a localized, or rank one, perturbation caused by the (core) hole left behind after the photo-excitation of an electron into the conduction band. The photo-absorption spectra result from the competition between two many-body responses, Anderson's orthogonality catastrophe and the Mahan-Nozieres-DeDominicis contribution. Both mechanisms depend on the system size through the number of particles and, more importantly, fluctuations produced by the coherence characteristic of mesoscopic samples. The latter lead to a modification of the dipole matrix element and trigger one of our key results: a rounded K-edge typically found in metals will turn into a (slightly) peaked edge on average in the mesoscopic regime. We consider in detail the effect of the "bound state" produced by the core hole.Comment: 16 page

Heat capacity of the quantum magnet TiOCl

Measurements of the heat capacity C(T,H) of the one-dimensional quantum magnet TiOCl are presented for temperatures 2K < T < 300K and magnetic fields up to 5T. Distinct anomalies at 91K and 67K signal two subsequent phase transitions. The lower of these transitions clearly is of first order and seems to be related to the spin degrees of freedom. The transition at 92K probably involves the lattice and/or orbital moments. A detailed analysis of the data reveals that the entropy change through both transitions is surprisingly small (~ 0.1R), pointing to the existence strong fluctuations well into the non-ordered high-temperature phase. No significant magnetic field dependence was detected.Comment: 4 pages, 2 figure

Disclinations, dislocations and continuous defects: a reappraisal

Disclinations, first observed in mesomorphic phases, are relevant to a number of ill-ordered condensed matter media, with continuous symmetries or frustrated order. They also appear in polycrystals at the edges of grain boundaries. They are of limited interest in solid single crystals, where, owing to their large elastic stresses, they mostly appear in close pairs of opposite signs. The relaxation mechanisms associated with a disclination in its creation, motion, change of shape, involve an interplay with continuous or quantized dislocations and/or continuous disclinations. These are attached to the disclinations or are akin to Nye's dislocation densities, well suited here. The notion of 'extended Volterra process' takes these relaxation processes into account and covers different situations where this interplay takes place. These concepts are illustrated by applications in amorphous solids, mesomorphic phases and frustrated media in their curved habit space. The powerful topological theory of line defects only considers defects stable against relaxation processes compatible with the structure considered. It can be seen as a simplified case of the approach considered here, well suited for media of high plasticity or/and complex structures. Topological stability cannot guarantee energetic stability and sometimes cannot distinguish finer details of structure of defects.Comment: 72 pages, 36 figure

FERN – a Java framework for stochastic simulation and evaluation of reaction networks

<p>Abstract</p> <p>Background</p> <p>Stochastic simulation can be used to illustrate the development of biological systems over time and the stochastic nature of these processes. Currently available programs for stochastic simulation, however, are limited in that they either a) do not provide the most efficient simulation algorithms and are difficult to extend, b) cannot be easily integrated into other applications or c) do not allow to monitor and intervene during the simulation process in an easy and intuitive way. Thus, in order to use stochastic simulation in innovative high-level modeling and analysis approaches more flexible tools are necessary.</p> <p>Results</p> <p>In this article, we present FERN (Framework for Evaluation of Reaction Networks), a Java framework for the efficient simulation of chemical reaction networks. FERN is subdivided into three layers for network representation, simulation and visualization of the simulation results each of which can be easily extended. It provides efficient and accurate state-of-the-art stochastic simulation algorithms for well-mixed chemical systems and a powerful observer system, which makes it possible to track and control the simulation progress on every level. To illustrate how FERN can be easily integrated into other systems biology applications, plugins to Cytoscape and CellDesigner are included. These plugins make it possible to run simulations and to observe the simulation progress in a reaction network in real-time from within the Cytoscape or CellDesigner environment.</p> <p>Conclusion</p> <p>FERN addresses shortcomings of currently available stochastic simulation programs in several ways. First, it provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. FERN's implementations are considerably faster than the C implementations of gillespie2 or the Java implementations of ISBJava. Second, it can be used in a straightforward way both as a stand-alone program and within new systems biology applications. Finally, complex scenarios requiring intervention during the simulation progress can be modelled easily with FERN.</p