AlignHUSH: Alignment of HMMs using structure and hydrophobicity information

Background: Sensitive remote homology detection and accurate alignments especially in the midnight zone of sequence similarity are needed for better function annotation and structural modeling of proteins. An algorithm, AlignHUSH for HMM-HMM alignment has been developed which is capable of recognizing distantly related domain families The method uses structural information, in the form of predicted secondary structure probabilities, and hydrophobicity of amino acids to align HMMs of two sets of aligned sequences. The effect of using adjoining column(s) information has also been investigated and is found to increase the sensitivity of HMM-HMM alignments and remote homology detection. Results: We have assessed the performance of AlignHUSH using known evolutionary relationships available in SCOP. AlignHUSH performs better than the best HMM-HMM alignment methods and is observed to be even more sensitive at higher error rates. Accuracy of the alignments obtained using AlignHUSH has been assessed using the structure-based alignments available in BaliBASE. The alignment length and the alignment quality are found to be appropriate for homology modeling and function annotation. The alignment accuracy is found to be comparable to existing methods for profile-profile alignments. Conclusions: A new method to align HMMs has been developed and is shown to have better sensitivity at error rates of 10% and above when compared to other available programs. The proposed method could effectively aid obtaining clues to functions of proteins of yet unknown function. A web-server incorporating the AlignHUSH method is available at http://crick.mbu.iisc.ernet.in/similar to alignhush/

Turbulence measurements in an ‘equilibrium’ axisymmetric wall jet Journal

This paper reports measurements of turbulent quantities in an axisymmetric wall jet subjected to an adverse pressure gradient in a conical diffuser, in such a way that a suitably defined pressure-gradient parameter is everywhere small. Self-similarity is observed in the mean velocity profile, as well as the profiles of many turbulent quantities at sufficiently large distances from the injection slot. Autocorrelation measurements indicate that, in the region of turbulent production, the time scale of ν fluctuations is very much smaller than the time scale of u fluctuations. Based on the data on these time scales, a possible model is proposed for the Reynolds stress. One-dimensional energy spectra are obtained for the u, v and w components at several points in the wall jet. It is found that self-similarity is exhibited by the one-dimensional wavenumber spectrum of $\overline{q^2}(=\overline{u^2}+\overline{v^2}+\overline{w^2})$, if the half-width of the wall jet and the local mean velocity are used for forming the non-dimensional wavenumber. Both the autocorrelation curves and the spectra indicate the existence of periodicity in the flow. The rate of dissipation of turbulent energy is estimated from the $\overline{q^2}$ spectra, using a slightly modified version of a previously suggested method.

Effect of longitudinal surface curvature on boundary layers

We consider here the higher order effect of moderate longitudinal surface curvature on steady, two-dimensional, incompressible laminar boundary layers. The basic partial differential equations for the problem, derived by the method of matched asymptotic expansions, are found to possess similarity solutions for a family of surface curvatures and pressure gradients. The similarity equations obtained by this anaylsis have been solved numerically on a computer, and show a definite decrease in skin friction when the surface has convex curvature in all cases including zero pressure gradient. Typical velocity profiles and some relevant boundary-layer characteristics are tabulated, and a critical comparison with previous work is given.

Some properties of boundary layer flow during the transition from laminar to turbulent motion

Transition in the boundary layer on a flat plate is examined from the point of view of intermittent production of turbulent spots. On the hypothesis of localized laminar breakdown, for which there is some expermental evidence, Emmons’ probability calculations can be extended to explain the observed statistical similarity of transition regions. Application of these ideas allows detailed calculations of the boundary layer parameters including mean velocity profiles and skin friction during transition. The mean velocity profiles belong to a universal one-parameter family with the intermittency factor as the parameter. From an examination of experimental data the probable existence of a relation between the transition Reynolds number and the rate of production of the turbulent spots is deduced. A simple new technique for the measurement of the intermittency factor by a Pitot tube is reported.

On the criteria for reverse transition in a two-dimensional boundary layer flow

Experiments on reverse transition were conducted in two-dimensional accelerated incompressible turbulent boundary layers. Mean velocity profiles, longitudinal velocity fluctuations $\tilde{u}^{\prime}(=(\overline{u^{\prime 2}})^{\frac{1}{2}})$ and the wall-shearing stress (TW) were measured. The mean velocity profiles show that the wall region adjusts itself to laminar conditions earlier than the outer region. During the reverse transition process, increases in the shape parameter (H) are accompanied by a decrease in the skin friction coefficient (Cf). Profiles of turbulent intensity (u’2) exhibit near similarity in the turbulence decay region. The breakdown of the law of the wall is characterized by the parameter \[ \Delta_p (=\nu[dP/dx]/\rho U^{*3}) = - 0.02, \] where U* is the friction velocity. Downstream of this region the decay of $\tilde{u}^{\prime}$ fluctuations occurred when the momentum thickness Reynolds number (R) decreased roughly below 400.

PocketAlign A Novel Algorithm for Aligning Binding Sites in Protein Structures

A fundamental task in bioinformatics involves a transfer of knowledge from one protein molecule onto another by way of recognizing similarities. Such similarities are obtained at different levels, that of sequence, whole fold, or important substructures. Comparison of binding sites is important to understand functional similarities among the proteins and also to understand drug cross-reactivities. Current methods in literature have their own merits and demerits, warranting exploration of newer concepts and algorithms, especially for large-scale comparisons and for obtaining accurate residue-wise mappings. Here, we report the development of a new algorithm, PocketAlign, for obtaining structural superpositions of binding sites. The software is available as a web-service at http://proline.physicslisc.emetin/pocketalign/. The algorithm encodes shape descriptors in the form of geometric perspectives, supplemented by chemical group classification. The shape descriptor considers several perspectives with each residue as the focus and captures relative distribution of residues around it in a given site. Residue-wise pairings are computed by comparing the set of perspectives of the first site with that of the second, followed by a greedy approach that incrementally combines residue pairings into a mapping. The mappings in different frames are then evaluated by different metrics encoding the extent of alignment of individual geometric perspectives. Different initial seed alignments are computed, each subsequently extended by detecting consequential atomic alignments in a three-dimensional grid, and the best 500 stored in a database. Alignments are then ranked, and the top scoring alignments reported, which are then streamed into Pymol for visualization and analyses. The method is validated for accuracy and sensitivity and benchmarked against existing methods. An advantage of PocketAlign, as compared to some of the existing tools available for binding site comparison in literature, is that it explores different schemes for identifying an alignment thus has a better potential to capture similarities in ligand recognition abilities. PocketAlign, by finding a detailed alignment of a pair of sites, provides insights as to why two sites are similar and which set of residues and atoms contribute to the similarity.

Identification of a core promoter and a novel isoform of the human TSCI gene transcript and structural comparison with mouse homolog

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with loci on chromosome 9q34.12 (TSC1) and chromosome 16p13.3 (TSC2). Genes for both loci have been isolated and characterized. The promoters of both genes have not been characterized so far and little is known about the regulation of these genes. This study reports the characterization of the human TSC1 promoter region for the first time. We have identified a novel alternative isoform in the 5' untranslated region (UTR) of the TSC1 gene transcript involving exon 1. Alternative isoforms in the 5' UTR of the mouse Tsc1 gene transcript involving exon I and exon 2 have also been identified. We have identified three upstream open reading frames (uORFs) in the 5' UTR of the TSC1/Tsc1 gene. A comparative study of the 5' UTR of TSC1/Tsc1 gene has revealed that there is a high degree of similarity not only in the sequence but also in the splicing pattern of both human and mouse TSC1 genes. We have used PCR methodology to isolate approximately 1.6 kb genomic DNA 5' to the TSC1 cDNA. This sequence has directed a high level of expression of luciferase activity in both HeLa and HepG2 cells. Successive 5' and 3' deletion analysis has suggested that a -587 bp region, from position +77 to -510 from the transcription start site (TSS), contains the promoter activity. Interestingly, this region contains no consensus TATA box or CAAT box. However, a 521-bp fragment surrounding the TSS exhibits the characteristics of a CpG island which overlaps with the promoter region. The identification of the TSC1 promoter region will help in designing a suitable strategy to identify mutations in this region in patients who do not show any mutations in the coding regions. It will also help to study the regulation of the TSC1 gene and its role in tumorigenesis. (C) 2003 Elsevier B.V. All rights reserved.

The beta-glucoside genes of Klebsiella aerogenes: conservation and divergence in relation to the cryptic bgl genes of Escherichia coli

The ability to metabolize aromatic beta-glucosides such as salicin and arbutin varies among members of the Enterobacteriaceae. The ability of Escherichia coli to degrade salicin and arbutin appears to be cryptic, subject to activation of the bgl genes, whereas many members of the Klebsiella genus can metabolize these sugars. We have examined the genetic basis for beta-glucoside utilization in Klebsiella aerogenes. The Klebsiella equivalents of bglG, bglB and bglR have been cloned using the genome sequence database of Klebsiella pneumoniae. Nucleotide sequencing shows that the K. aerogenes bgl genes show substantial similarities to the E. coli counterparts. The K. aerogenes bgl genes in multiple copies can also complement E. coli mutants deficient in bglG encoding the antiterminator and bglB encoding the phospho-beta-glucosidase, suggesting that they are functional homologues. The regulatory region bglR of K aerogenes shows a high degree of similarity of the sequences involved in BglG-mediated regulation. Interestingly, the regions corresponding to the negative elements present in the E. coli regulatory region show substantial divergence in K aerogenes. The possible evolutionary implications of the results are discussed. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.v. All rights reserved.

Improvement of protein structure comparison using a structural alphabet

The three dimensional structure of a protein provides major insights into its function. Protein structure comparison has implications in functional and evolutionary studies. A structural alphabet (SA) is a library of local protein structure prototypes that can abstract every part of protein main chain conformation. Protein Blocks (PBS) is a widely used SA, composed of 16 prototypes, each representing a pentapeptide backbone conformation defined in terms of dihedral angles. Through this description, the 3D structural information can be translated into a 1D sequence of PBs. In a previous study, we have used this approach to compare protein structures encoded in terms of PBs. A classical sequence alignment procedure based on dynamic programming was used, with a dedicated PB Substitution Matrix (SM). PB-based pairwise structural alignment method gave an excellent performance, when compared to other established methods for mining. In this study, we have (i) refined the SMs and (ii) improved the Protein Block Alignment methodology (named as iPBA). The SM was normalized in regards to sequence and structural similarity. Alignment of protein structures often involves similar structural regions separated by dissimilar stretches. A dynamic programming algorithm that weighs these local similar stretches has been designed. Amino acid substitutions scores were also coupled linearly with the PB substitutions. iPBA improves (i) the mining efficiency rate by 6.8% and (ii) more than 82% of the alignments have a better quality. A higher efficiency in aligning multi-domain proteins could be also demonstrated. The quality of alignment is better than DALI and MUSTANG in 81.3% of the cases. Thus our study has resulted in an impressive improvement in the quality of protein structural alignment. (C) 2011 Elsevier Masson SAS. All rights reserved.

Online Unsupervised Pattern Discovery in Speech Using Parallelization

Segmental dynamic time warping (DTW) has been demonstrated to be a useful technique for finding acoustic similarity scores between segments of two speech utterances. Due to its high computational requirements, it had to be computed in an offline manner, limiting the applications of the technique. In this paper, we present results of parallelization of this task by distributing the workload in either a static or dynamic way on an 8-processor cluster and discuss the trade-offs among different distribution schemes. We show that online unsupervised pattern discovery using segmental DTW is plausible with as low as 8 processors. This brings the task within reach of today's general purpose multi-core servers. We also show results on a 32-processor system, and discuss factors affecting scalability of our methods.

Method of Design Through Structuring of Meanings

This research shows a new approach and development of a design methodology, based on the perspective of meanings. In this study the design process is explored as a development of the structure of meanings. The processes of search and evaluation of meanings form the foundations of developing this structure. In order to facilitate the use and operation of the meanings, the WordNet lexical database and an existing visualization of WordNet — Visuwords — is used for the process of meaning search. The basic tool used for evaluation process is the WordNet::Similarity software, measuring the relatedness of meanings in the database. In this way it is measuring the degree of interconnections between different meanings. This kind of search and evaluation techniques are later on incorporated into our methodology of the structure of meanings to support the design process. The measures of relatedness of meanings are developed as convergence criteria for application in the processes of evaluation. Further on, the methodology for the structure of meanings developed here is used to construct meanings in a verification of product design. The steps of the design methodology, including the search and evaluation processes involved in developing the structure of the meanings, are elucidated. The choices, made by the designer in terms of meanings are supported by consequent searches and evaluations of meanings to be implemented in the designed product. In conclusion, the paper presents directions for developing and further extensions of the proposed design methodology.

Structural Alignment based Kernels for Protein Structure Classification

Structural alignments are the most widely used tools for comparing proteins with low sequence similarity. The main contribution of this paper is to derive various kernels on proteins from structural alignments, which do not use sequence information. Central to the kernels is a novel alignment algorithm which matches substructures of fixed size using spectral graph matching techniques. We derive positive semi-definite kernels which capture the notion of similarity between substructures. Using these as base more sophisticated kernels on protein structures are proposed. To empirically evaluate the kernels we used a 40% sequence non-redundant structures from 15 different SCOP superfamilies. The kernels when used with SVMs show competitive performance with CE, a state of the art structure comparison program.

Interaction anisotropy and shear instability of aspirin polymorphs established by nanoindentation

Nanoindentation is applied to the two polymorphs of aspirin to examine and differentiate their interaction anisotropy and shear instability. Aspirin provides an excellent test system for the technique because: (i) polymorphs I and II exhibit structural similarity in two dimensions, thereby facilitating clear examination of the differences in mechanical response in relation to well-defined differences between the two crystal structures; (ii) single crystals of the metastable polymorph II have only recently become accessible; (iii) shear instability has been proposed for II. Different elastic moduli and hardness values determined for the two polymorphs are correlated with their crystal structures, and the interpretation is supported by measured thermal expansion coefficients. The stress-induced transformation of the metastable polymorph II to the stable polymorph I can be brought about rapidly by mechanical milling, and proceeds via a slip mechanism. This work establishes that nanoindentation provides ``signature'' responses for the two aspirin polymorphs, despite their very similar crystal structures. It also demonstrates the value of the technique to quantify stability relationships and phase transformations in molecular crystals, enabling a deeper understanding of polymorphism in the context of crystal engineering.

Methods for Automatic Evaluation of Sentence Extract Summaries

This paper describes three novel techniques to automatically evaluate sentence extract summaries. Two of these techniques called FuSE and DeFuSE evaluate the quality of the generated extract summary based on the degree of similarity to the model summary. They use a fuzzy set theoretic basis to generate a match score. DeFuSE is an enhancement to FuSE and uses WordNet based hypernymy structures to detect similarity between sentences at abstracted levels. The third technique focuses on quantifying the quality of an extract summary based on the difficulty in generating such a summary. Advantages of these techniques are described with examples.

Symmetry in Scalar Field Topology

Study of symmetric or repeating patterns in scalar fields is important in scientific data analysis because it gives deep insights into the properties of the underlying phenomenon. Though geometric symmetry has been well studied within areas like shape processing, identifying symmetry in scalar fields has remained largely unexplored due to the high computational cost of the associated algorithms. We propose a computationally efficient algorithm for detecting symmetric patterns in a scalar field distribution by analysing the topology of level sets of the scalar field. Our algorithm computes the contour tree of a given scalar field and identifies subtrees that are similar. We define a robust similarity measure for comparing subtrees of the contour tree and use it to group similar subtrees together. Regions of the domain corresponding to subtrees that belong to a common group are extracted and reported to be symmetric. Identifying symmetry in scalar fields finds applications in visualization, data exploration, and feature detection. We describe two applications in detail: symmetry-aware transfer function design and symmetry-aware isosurface extraction.