Improvement in accuracy of multiple sequence alignment using novel group-to-group sequence alignment algorithm with piecewise linear gap cost

BACKGROUND: Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels. RESULTS: We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee. CONCLUSION: PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at

Fast Hierarchical Clustering and Other Applications of Dynamic Closest Pairs

We develop data structures for dynamic closest pair problems with arbitrary distance functions, that do not necessarily come from any geometric structure on the objects. Based on a technique previously used by the author for Euclidean closest pairs, we show how to insert and delete objects from an n-object set, maintaining the closest pair, in O(n log^2 n) time per update and O(n) space. With quadratic space, we can instead use a quadtree-like structure to achieve an optimal time bound, O(n) per update. We apply these data structures to hierarchical clustering, greedy matching, and TSP heuristics, and discuss other potential applications in machine learning, Groebner bases, and local improvement algorithms for partition and placement problems. Experiments show our new methods to be faster in practice than previously used heuristics.Comment: 20 pages, 9 figures. A preliminary version of this paper appeared at the 9th ACM-SIAM Symp. on Discrete Algorithms, San Francisco, 1998, pp. 619-628. For source code and experimental results, see http://www.ics.uci.edu/~eppstein/projects/pairs

Dynamical model based on finite stacking enthalpies for homogeneous and inhomogeneous DNA thermal denaturation

We present a nonlinear dynamical model for DNA thermal denaturation, which is based on the finite stacking enthalpies used in thermodynamical nearest-neighbour calculations. Within this model, the finiteness of stacking enthalpies is shown to be responsible for the sharpness of calculated melting curves. Transfer-integral and molecular dynamics calculations are performed to demonstrate that the proposed model leads to good agreement with known experimental results for both homogeneous and inhomogeneous DNA

L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study

Nitric oxide (NO) is synthesized from a unique precursor, arginine, by nitric oxide synthase (NOS). In brain cells, arginine is supplied by protein breakdown or extracted from the blood through cationic amino acid transporters (CATs). Arginine can also be recycled from the citrulline produced by NOS activity, through argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) activities, and metabolized by arginase. NOS, AS and AL constitute the so-called citrulline-NO cycle. In order to better understand arginine transport, recycling and degradation, we studied the regional distribution of cells expressing CAT1, CAT3, AS, AL, neuronal NOS (nNOS) and arginase II (AII) in the adult rat brain by non-radioisotopic in situ hybridization (ISH). CAT1, AL and AII presented an ubiquitous neuronal and glial expression, whereas CAT3 and AS were confined to neurons. nNOS was restricted to scattered neurons and a few brain nuclei and layers. We demonstrate by this study that cells expressing nNOS all appear to express the entire citrulline-NO cycle, whereas numerous cells expressing AL do not express AS. The differential expression of these genes within the same anatomical structure could indicate that intercellular exchanges of citrulline-NO cycle metabolites are relevant. Thus vicinal interactions should be taken into account to study their regulatory mechanisms

Differential expression of the cationic amino acid transporter 2(B) in the adult rat brain

L-Arginine is a substrate for the synthesis of proteins, nitric oxide (NO), creatine, urea, proline, glutamate, polyamines and agmatine. In the central nervous system (CNS), arginine is extracted from the blood and exchanged by cells through carriers called cationic amino acid transporters (CAT) and belonging to the so-called system y+. In order to better understand the arginine transport in the CNS, we studied in detail the regional distribution of the cells expressing the CAT2(B) transcript in the adult rat brain by non-radioisotopic in situ hybridization. We show that CAT2(B) is expressed in neurons and oligodendrocytes throughout the brain, but is not detected in astrocytes. The pattern of localization of CAT2(B) in the normal adult rat brain fits closely that of CRT1, a specific creatine transporter. Our study demonstrates that the in vivo expression of CAT2(B) differs from that reported in vitro, implying that local cellular interactions should be taken into account in studies of gene regulation of the CAT2(B) gene. Our work suggests that CAT2(B) may play a role in case of increased NO production as well as arginine or creatine deficiency in the brain

Accelerating exhaustive pairwise metagenomic comparisons

In this manuscript, we present an optimized and parallel version of our previous work IMSAME, an exhaustive gapped aligner for the pairwise and accurate comparison of metagenomes. Parallelization strategies are applied to take advantage of modern multiprocessor architectures. In addition, sequential optimizations in CPU time and memory consumption are provided. These algorithmic and computational enhancements enable IMSAME to calculate near optimal alignments which are used to directly assess similarity between metagenomes without requiring reference databases. We show that the overall efficiency of the parallel implementation is superior to 80% while retaining scalability as the number of parallel cores used increases. Moreover, we also show thats equential optimizations yield up to 8x speedup for scenarios with larger data.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Multiple sequence alignment based on set covers

We introduce a new heuristic for the multiple alignment of a set of sequences. The heuristic is based on a set cover of the residue alphabet of the sequences, and also on the determination of a significant set of blocks comprising subsequences of the sequences to be aligned. These blocks are obtained with the aid of a new data structure, called a suffix-set tree, which is constructed from the input sequences with the guidance of the residue-alphabet set cover and generalizes the well-known suffix tree of the sequence set. We provide performance results on selected BAliBASE amino-acid sequences and compare them with those yielded by some prominent approaches

Turbulence-induced melting of a nonequilibrium vortex crystal in a forced thin fluid film

To develop an understanding of recent experiments on the turbulence-induced melting of a periodic array of vortices in a thin fluid film, we perform a direct numerical simulation of the two-dimensional Navier-Stokes equations forced such that, at low Reynolds numbers, the steady state of the film is a square lattice of vortices. We find that, as we increase the Reynolds number, this lattice undergoes a series of nonequilibrium phase transitions, first to a crystal with a different reciprocal lattice and then to a sequence of crystals that oscillate in time. Initially the temporal oscillations are periodic; this periodic behaviour becomes more and more complicated, with increasing Reynolds number, until the film enters a spatially disordered nonequilibrium statistical steady that is turbulent. We study this sequence of transitions by using fluid-dynamics measures, such as the Okubo-Weiss parameter that distinguishes between vortical and extensional regions in the flow, ideas from nonlinear dynamics, e.g., \Poincare maps, and theoretical methods that have been developed to study the melting of an equilibrium crystal or the freezing of a liquid and which lead to a natural set of order parameters for the crystalline phases and spatial autocorrelation functions that characterise short- and long-range order in the turbulent and crystalline phases, respectively.Comment: 31 pages, 56 figures, movie files not include

Large-Eddy Simulations of Fluid and Magnetohydrodynamic Turbulence Using Renormalized Parameters

In this paper a procedure for large-eddy simulation (LES) has been devised for fluid and magnetohydrodynamic turbulence in Fourier space using the renormalized parameters. The parameters calculated using field theory have been taken from recent papers by Verma [Phys. Rev. E, 2001; Phys. Plasmas, 2001]. We have carried out LES on $64^3$ grid. These results match quite well with direct numerical simulations of $128^3$. We show that proper choice of parameter is necessary in LES.Comment: 12 pages, 4 figures: Proper figures inserte