ProfileGrids: a sequence alignment visualization paradigm that avoids the limitations of Sequence Logos.

PubMed

Roca, Alberto I

2014-01-01

The 2013 BioVis Contest provided an opportunity to evaluate different paradigms for visualizing protein multiple sequence alignments. Such data sets are becoming extremely large and thus taxing current visualization paradigms. Sequence Logos represent consensus sequences but have limitations for protein alignments. As an alternative, ProfileGrids are a new protein sequence alignment visualization paradigm that represents an alignment as a color-coded matrix of the residue frequency occurring at every homologous position in the aligned protein family. The JProfileGrid software program was used to analyze the BioVis contest data sets to generate figures for comparison with the Sequence Logo reference images. The ProfileGrid representation allows for the clear and effective analysis of protein multiple sequence alignments. This includes both a general overview of the conservation and diversity sequence patterns as well as the interactive ability to query the details of the protein residue distributions in the alignment. The JProfileGrid software is free and available from http://www.ProfileGrid.org.

Phylo-mLogo: an interactive and hierarchical multiple-logo visualization tool for alignment of many sequences

PubMed Central

Shih, Arthur Chun-Chieh; Lee, DT; Peng, Chin-Lin; Wu, Yu-Wei

2007-01-01

Background When aligning several hundreds or thousands of sequences, such as epidemic virus sequences or homologous/orthologous sequences of some big gene families, to reconstruct the epidemiological history or their phylogenies, how to analyze and visualize the alignment results of many sequences has become a new challenge for computational biologists. Although there are several tools available for visualization of very long sequence alignments, few of them are applicable to the alignments of many sequences. Results A multiple-logo alignment visualization tool, called Phylo-mLogo, is presented in this paper. Phylo-mLogo calculates the variabilities and homogeneities of alignment sequences by base frequencies or entropies. Different from the traditional representations of sequence logos, Phylo-mLogo not only displays the global logo patterns of the whole alignment of multiple sequences, but also demonstrates their local homologous logos for each clade hierarchically. In addition, Phylo-mLogo also allows the user to focus only on the analysis of some important, structurally or functionally constrained sites in the alignment selected by the user or by built-in automatic calculation. Conclusion With Phylo-mLogo, the user can symbolically and hierarchically visualize hundreds of aligned sequences simultaneously and easily check the changes of their amino acid sites when analyzing many homologous/orthologous or influenza virus sequences. More information of Phylo-mLogo can be found at URL . PMID:17319966

A simplified implementation of edge detection in MATLAB is faster and more sensitive than fast fourier transform for actin fiber alignment quantification.

PubMed

Kemeny, Steven Frank; Clyne, Alisa Morss

2011-04-01

Fiber alignment plays a critical role in the structure and function of cells and tissues. While fiber alignment quantification is important to experimental analysis and several different methods for quantifying fiber alignment exist, many studies focus on qualitative rather than quantitative analysis perhaps due to the complexity of current fiber alignment methods. Speed and sensitivity were compared in edge detection and fast Fourier transform (FFT) for measuring actin fiber alignment in cells exposed to shear stress. While edge detection using matrix multiplication was consistently more sensitive than FFT, image processing time was significantly longer. However, when MATLAB functions were used to implement edge detection, MATLAB's efficient element-by-element calculations and fast filtering techniques reduced computation cost 100 times compared to the matrix multiplication edge detection method. The new computation time was comparable to the FFT method, and MATLAB edge detection produced well-distributed fiber angle distributions that statistically distinguished aligned and unaligned fibers in half as many sample images. When the FFT sensitivity was improved by dividing images into smaller subsections, processing time grew larger than the time required for MATLAB edge detection. Implementation of edge detection in MATLAB is simpler, faster, and more sensitive than FFT for fiber alignment quantification.

Bellerophon: a program to detect chimeric sequences in multiple sequence alignments.

PubMed

Huber, Thomas; Faulkner, Geoffrey; Hugenholtz, Philip

2004-09-22

Bellerophon is a program for detecting chimeric sequences in multiple sequence datasets by an adaption of partial treeing analysis. Bellerophon was specifically developed to detect 16S rRNA gene chimeras in PCR-clone libraries of environmental samples but can be applied to other nucleotide sequence alignments. Bellerophon is available as an interactive web server at http://foo.maths.uq.edu.au/~huber/bellerophon.pl

Customisation of the exome data analysis pipeline using a combinatorial approach.

PubMed

Pattnaik, Swetansu; Vaidyanathan, Srividya; Pooja, Durgad G; Deepak, Sa; Panda, Binay

2012-01-01

The advent of next generation sequencing (NGS) technologies have revolutionised the way biologists produce, analyse and interpret data. Although NGS platforms provide a cost-effective way to discover genome-wide variants from a single experiment, variants discovered by NGS need follow up validation due to the high error rates associated with various sequencing chemistries. Recently, whole exome sequencing has been proposed as an affordable option compared to whole genome runs but it still requires follow up validation of all the novel exomic variants. Customarily, a consensus approach is used to overcome the systematic errors inherent to the sequencing technology, alignment and post alignment variant detection algorithms. However, the aforementioned approach warrants the use of multiple sequencing chemistry, multiple alignment tools, multiple variant callers which may not be viable in terms of time and money for individual investigators with limited informatics know-how. Biologists often lack the requisite training to deal with the huge amount of data produced by NGS runs and face difficulty in choosing from the list of freely available analytical tools for NGS data analysis. Hence, there is a need to customise the NGS data analysis pipeline to preferentially retain true variants by minimising the incidence of false positives and make the choice of right analytical tools easier. To this end, we have sampled different freely available tools used at the alignment and post alignment stage suggesting the use of the most suitable combination determined by a simple framework of pre-existing metrics to create significant datasets.

A distributed system for fast alignment of next-generation sequencing data.

PubMed

Srimani, Jaydeep K; Wu, Po-Yen; Phan, John H; Wang, May D

2010-12-01

We developed a scalable distributed computing system using the Berkeley Open Interface for Network Computing (BOINC) to align next-generation sequencing (NGS) data quickly and accurately. NGS technology is emerging as a promising platform for gene expression analysis due to its high sensitivity compared to traditional genomic microarray technology. However, despite the benefits, NGS datasets can be prohibitively large, requiring significant computing resources to obtain sequence alignment results. Moreover, as the data and alignment algorithms become more prevalent, it will become necessary to examine the effect of the multitude of alignment parameters on various NGS systems. We validate the distributed software system by (1) computing simple timing results to show the speed-up gained by using multiple computers, (2) optimizing alignment parameters using simulated NGS data, and (3) computing NGS expression levels for a single biological sample using optimal parameters and comparing these expression levels to that of a microarray sample. Results indicate that the distributed alignment system achieves approximately a linear speed-up and correctly distributes sequence data to and gathers alignment results from multiple compute clients.

ProfileGrids: a sequence alignment visualization paradigm that avoids the limitations of Sequence Logos

PubMed Central

2014-01-01

Background The 2013 BioVis Contest provided an opportunity to evaluate different paradigms for visualizing protein multiple sequence alignments. Such data sets are becoming extremely large and thus taxing current visualization paradigms. Sequence Logos represent consensus sequences but have limitations for protein alignments. As an alternative, ProfileGrids are a new protein sequence alignment visualization paradigm that represents an alignment as a color-coded matrix of the residue frequency occurring at every homologous position in the aligned protein family. Results The JProfileGrid software program was used to analyze the BioVis contest data sets to generate figures for comparison with the Sequence Logo reference images. Conclusions The ProfileGrid representation allows for the clear and effective analysis of protein multiple sequence alignments. This includes both a general overview of the conservation and diversity sequence patterns as well as the interactive ability to query the details of the protein residue distributions in the alignment. The JProfileGrid software is free and available from http://www.ProfileGrid.org. PMID:25237393

Multi-profile Bayesian alignment model for LC-MS data analysis with integration of internal standards

PubMed Central

Tsai, Tsung-Heng; Tadesse, Mahlet G.; Di Poto, Cristina; Pannell, Lewis K.; Mechref, Yehia; Wang, Yue; Ressom, Habtom W.

2013-01-01

Motivation: Liquid chromatography-mass spectrometry (LC-MS) has been widely used for profiling expression levels of biomolecules in various ‘-omic’ studies including proteomics, metabolomics and glycomics. Appropriate LC-MS data preprocessing steps are needed to detect true differences between biological groups. Retention time (RT) alignment, which is required to ensure that ion intensity measurements among multiple LC-MS runs are comparable, is one of the most important yet challenging preprocessing steps. Current alignment approaches estimate RT variability using either single chromatograms or detected peaks, but do not simultaneously take into account the complementary information embedded in the entire LC-MS data. Results: We propose a Bayesian alignment model for LC-MS data analysis. The alignment model provides estimates of the RT variability along with uncertainty measures. The model enables integration of multiple sources of information including internal standards and clustered chromatograms in a mathematically rigorous framework. We apply the model to LC-MS metabolomic, proteomic and glycomic data. The performance of the model is evaluated based on ground-truth data, by measuring correlation of variation, RT difference across runs and peak-matching performance. We demonstrate that Bayesian alignment model improves significantly the RT alignment performance through appropriate integration of relevant information. Availability and implementation: MATLAB code, raw and preprocessed LC-MS data are available at http://omics.georgetown.edu/alignLCMS.html Contact: hwr@georgetown.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24013927

Simultaneous phylogeny reconstruction and multiple sequence alignment

PubMed Central

Yue, Feng; Shi, Jian; Tang, Jijun

2009-01-01

Background A phylogeny is the evolutionary history of a group of organisms. To date, sequence data is still the most used data type for phylogenetic reconstruction. Before any sequences can be used for phylogeny reconstruction, they must be aligned, and the quality of the multiple sequence alignment has been shown to affect the quality of the inferred phylogeny. At the same time, all the current multiple sequence alignment programs use a guide tree to produce the alignment and experiments showed that good guide trees can significantly improve the multiple alignment quality. Results We devise a new algorithm to simultaneously align multiple sequences and search for the phylogenetic tree that leads to the best alignment. We also implemented the algorithm as a C program package, which can handle both DNA and protein data and can take simple cost model as well as complex substitution matrices, such as PAM250 or BLOSUM62. The performance of the new method are compared with those from other popular multiple sequence alignment tools, including the widely used programs such as ClustalW and T-Coffee. Experimental results suggest that this method has good performance in terms of both phylogeny accuracy and alignment quality. Conclusion We present an algorithm to align multiple sequences and reconstruct the phylogenies that minimize the alignment score, which is based on an efficient algorithm to solve the median problems for three sequences. Our extensive experiments suggest that this method is very promising and can produce high quality phylogenies and alignments. PMID:19208110

A novel approach to multiple sequence alignment using hadoop data grids.

PubMed

Sudha Sadasivam, G; Baktavatchalam, G

2010-01-01

Multiple alignment of protein sequences helps to determine evolutionary linkage and to predict molecular structures. The factors to be considered while aligning multiple sequences are speed and accuracy of alignment. Although dynamic programming algorithms produce accurate alignments, they are computation intensive. In this paper we propose a time efficient approach to sequence alignment that also produces quality alignment. The dynamic nature of the algorithm coupled with data and computational parallelism of hadoop data grids improves the accuracy and speed of sequence alignment. The principle of block splitting in hadoop coupled with its scalability facilitates alignment of very large sequences.

ADOMA: A Command Line Tool to Modify ClustalW Multiple Alignment Output.

PubMed

Zaal, Dionne; Nota, Benjamin

2016-01-01

We present ADOMA, a command line tool that produces alternative outputs from ClustalW multiple alignments of nucleotide or protein sequences. ADOMA can simplify the output of alignments by showing only the different residues between sequences, which is often desirable when only small differences such as single nucleotide polymorphisms are present (e.g., between different alleles). Another feature of ADOMA is that it can enhance the ClustalW output by coloring the residues in the alignment. This tool is easily integrated into automated Linux pipelines for next-generation sequencing data analysis, and may be useful for researchers in a broad range of scientific disciplines including evolutionary biology and biomedical sciences. The source code is freely available at https://sourceforge. net/projects/adoma/. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SARA-Coffee web server, a tool for the computation of RNA sequence and structure multiple alignments

PubMed Central

Di Tommaso, Paolo; Bussotti, Giovanni; Kemena, Carsten; Capriotti, Emidio; Chatzou, Maria; Prieto, Pablo; Notredame, Cedric

2014-01-01

This article introduces the SARA-Coffee web server; a service allowing the online computation of 3D structure based multiple RNA sequence alignments. The server makes it possible to combine sequences with and without known 3D structures. Given a set of sequences SARA-Coffee outputs a multiple sequence alignment along with a reliability index for every sequence, column and aligned residue. SARA-Coffee combines SARA, a pairwise structural RNA aligner with the R-Coffee multiple RNA aligner in a way that has been shown to improve alignment accuracy over most sequence aligners when enough structural data is available. The server can be accessed from http://tcoffee.crg.cat/apps/tcoffee/do:saracoffee. PMID:24972831

IVisTMSA: Interactive Visual Tools for Multiple Sequence Alignments.

PubMed

Pervez, Muhammad Tariq; Babar, Masroor Ellahi; Nadeem, Asif; Aslam, Naeem; Naveed, Nasir; Ahmad, Sarfraz; Muhammad, Shah; Qadri, Salman; Shahid, Muhammad; Hussain, Tanveer; Javed, Maryam

2015-01-01

IVisTMSA is a software package of seven graphical tools for multiple sequence alignments. MSApad is an editing and analysis tool. It can load 409% more data than Jalview, STRAP, CINEMA, and Base-by-Base. MSA comparator allows the user to visualize consistent and inconsistent regions of reference and test alignments of more than 21-MB size in less than 12 seconds. MSA comparator is 5,200% efficient and more than 40% efficient as compared to BALiBASE c program and FastSP, respectively. MSA reconstruction tool provides graphical user interfaces for four popular aligners and allows the user to load several sequence files at a time. FASTA generator converts seven formats of alignments of unlimited size into FASTA format in a few seconds. MSA ID calculator calculates identity matrix of more than 11,000 sequences with a sequence length of 2,696 base pairs in less than 100 seconds. Tree and Distance Matrix calculation tools generate phylogenetic tree and distance matrix, respectively, using neighbor joining% identity and BLOSUM 62 matrix.

Scalable multi-sample single-cell data analysis by Partition-Assisted Clustering and Multiple Alignments of Networks

PubMed Central

Samusik, Nikolay; Wang, Xiaowei; Guan, Leying; Nolan, Garry P.

2017-01-01

Mass cytometry (CyTOF) has greatly expanded the capability of cytometry. It is now easy to generate multiple CyTOF samples in a single study, with each sample containing single-cell measurement on 50 markers for more than hundreds of thousands of cells. Current methods do not adequately address the issues concerning combining multiple samples for subpopulation discovery, and these issues can be quickly and dramatically amplified with increasing number of samples. To overcome this limitation, we developed Partition-Assisted Clustering and Multiple Alignments of Networks (PAC-MAN) for the fast automatic identification of cell populations in CyTOF data closely matching that of expert manual-discovery, and for alignments between subpopulations across samples to define dataset-level cellular states. PAC-MAN is computationally efficient, allowing the management of very large CyTOF datasets, which are increasingly common in clinical studies and cancer studies that monitor various tissue samples for each subject. PMID:29281633

MACSIMS : multiple alignment of complete sequences information management system

PubMed Central

Thompson, Julie D; Muller, Arnaud; Waterhouse, Andrew; Procter, Jim; Barton, Geoffrey J; Plewniak, Frédéric; Poch, Olivier

2006-01-01

Background In the post-genomic era, systems-level studies are being performed that seek to explain complex biological systems by integrating diverse resources from fields such as genomics, proteomics or transcriptomics. New information management systems are now needed for the collection, validation and analysis of the vast amount of heterogeneous data available. Multiple alignments of complete sequences provide an ideal environment for the integration of this information in the context of the protein family. Results MACSIMS is a multiple alignment-based information management program that combines the advantages of both knowledge-based and ab initio sequence analysis methods. Structural and functional information is retrieved automatically from the public databases. In the multiple alignment, homologous regions are identified and the retrieved data is evaluated and propagated from known to unknown sequences with these reliable regions. In a large-scale evaluation, the specificity of the propagated sequence features is estimated to be >99%, i.e. very few false positive predictions are made. MACSIMS is then used to characterise mutations in a test set of 100 proteins that are known to be involved in human genetic diseases. The number of sequence features associated with these proteins was increased by 60%, compared to the features available in the public databases. An XML format output file allows automatic parsing of the MACSIM results, while a graphical display using the JalView program allows manual analysis. Conclusion MACSIMS is a new information management system that incorporates detailed analyses of protein families at the structural, functional and evolutionary levels. MACSIMS thus provides a unique environment that facilitates knowledge extraction and the presentation of the most pertinent information to the biologist. A web server and the source code are available at . PMID:16792820

Heuristics for multiobjective multiple sequence alignment.

PubMed

Abbasi, Maryam; Paquete, Luís; Pereira, Francisco B

2016-07-15

Aligning multiple sequences arises in many tasks in Bioinformatics. However, the alignments produced by the current software packages are highly dependent on the parameters setting, such as the relative importance of opening gaps with respect to the increase of similarity. Choosing only one parameter setting may provide an undesirable bias in further steps of the analysis and give too simplistic interpretations. In this work, we reformulate multiple sequence alignment from a multiobjective point of view. The goal is to generate several sequence alignments that represent a trade-off between maximizing the substitution score and minimizing the number of indels/gaps in the sum-of-pairs score function. This trade-off gives to the practitioner further information about the similarity of the sequences, from which she could analyse and choose the most plausible alignment. We introduce several heuristic approaches, based on local search procedures, that compute a set of sequence alignments, which are representative of the trade-off between the two objectives (substitution score and indels). Several algorithm design options are discussed and analysed, with particular emphasis on the influence of the starting alignment and neighborhood search definitions on the overall performance. A perturbation technique is proposed to improve the local search, which provides a wide range of high-quality alignments. The proposed approach is tested experimentally on a wide range of instances. We performed several experiments with sequences obtained from the benchmark database BAliBASE 3.0. To evaluate the quality of the results, we calculate the hypervolume indicator of the set of score vectors returned by the algorithms. The results obtained allow us to identify reasonably good choices of parameters for our approach. Further, we compared our method in terms of correctly aligned pairs ratio and columns correctly aligned ratio with respect to reference alignments. Experimental results show that our approaches can obtain better results than TCoffee and Clustal Omega in terms of the first ratio.

FASMA: a service to format and analyze sequences in multiple alignments.

PubMed

Costantini, Susan; Colonna, Giovanni; Facchiano, Angelo M

2007-12-01

Multiple sequence alignments are successfully applied in many studies for under- standing the structural and functional relations among single nucleic acids and protein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http://bioinformatica.isa.cnr.it/FASMA/.

MSAViewer: interactive JavaScript visualization of multiple sequence alignments.

PubMed

Yachdav, Guy; Wilzbach, Sebastian; Rauscher, Benedikt; Sheridan, Robert; Sillitoe, Ian; Procter, James; Lewis, Suzanna E; Rost, Burkhard; Goldberg, Tatyana

2016-11-15

The MSAViewer is a quick and easy visualization and analysis JavaScript component for Multiple Sequence Alignment data of any size. Core features include interactive navigation through the alignment, application of popular color schemes, sorting, selecting and filtering. The MSAViewer is 'web ready': written entirely in JavaScript, compatible with modern web browsers and does not require any specialized software. The MSAViewer is part of the BioJS collection of components. The MSAViewer is released as open source software under the Boost Software License 1.0. Documentation, source code and the viewer are available at http://msa.biojs.net/Supplementary information: Supplementary data are available at Bioinformatics online. msa@bio.sh. © The Author 2016. Published by Oxford University Press.

MSAViewer: interactive JavaScript visualization of multiple sequence alignments

PubMed Central

Yachdav, Guy; Wilzbach, Sebastian; Rauscher, Benedikt; Sheridan, Robert; Sillitoe, Ian; Procter, James; Lewis, Suzanna E.; Rost, Burkhard; Goldberg, Tatyana

2016-01-01

Summary: The MSAViewer is a quick and easy visualization and analysis JavaScript component for Multiple Sequence Alignment data of any size. Core features include interactive navigation through the alignment, application of popular color schemes, sorting, selecting and filtering. The MSAViewer is ‘web ready’: written entirely in JavaScript, compatible with modern web browsers and does not require any specialized software. The MSAViewer is part of the BioJS collection of components. Availability and Implementation: The MSAViewer is released as open source software under the Boost Software License 1.0. Documentation, source code and the viewer are available at http://msa.biojs.net/. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: msa@bio.sh PMID:27412096

mTM-align: a server for fast protein structure database search and multiple protein structure alignment.

PubMed

Dong, Runze; Pan, Shuo; Peng, Zhenling; Zhang, Yang; Yang, Jianyi

2018-05-21

With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop algorithms for efficient protein structure comparisons. In this article, we present the mTM-align server, which consists of two closely related modules: one for structure database search and the other for multiple structure alignment. The database search is speeded up based on a heuristic algorithm and a hierarchical organization of the structures in the database. The multiple structure alignment is performed using the recently developed algorithm mTM-align. Benchmark tests demonstrate that our algorithms outperform other peering methods for both modules, in terms of speed and accuracy. One of the unique features for the server is the interplay between database search and multiple structure alignment. The server provides service not only for performing fast database search, but also for making accurate multiple structure alignment with the structures found by the search. For the database search, it takes about 2-5 min for a structure of a medium size (∼300 residues). For the multiple structure alignment, it takes a few seconds for ∼10 structures of medium sizes. The server is freely available at: http://yanglab.nankai.edu.cn/mTM-align/.

DendroBLAST: approximate phylogenetic trees in the absence of multiple sequence alignments.

PubMed

Kelly, Steven; Maini, Philip K

2013-01-01

The rapidly growing availability of genome information has created considerable demand for both fast and accurate phylogenetic inference algorithms. We present a novel method called DendroBLAST for reconstructing phylogenetic dendrograms/trees from protein sequences using BLAST. This method differs from other methods by incorporating a simple model of sequence evolution to test the effect of introducing sequence changes on the reliability of the bipartitions in the inferred tree. Using realistic simulated sequence data we demonstrate that this method produces phylogenetic trees that are more accurate than other commonly-used distance based methods though not as accurate as maximum likelihood methods from good quality multiple sequence alignments. In addition to tests on simulated data, we use DendroBLAST to generate input trees for a supertree reconstruction of the phylogeny of the Archaea. This independent analysis produces an approximate phylogeny of the Archaea that has both high precision and recall when compared to previously published analysis of the same dataset using conventional methods. Taken together these results demonstrate that approximate phylogenetic trees can be produced in the absence of multiple sequence alignments, and we propose that these trees will provide a platform for improving and informing downstream bioinformatic analysis. A web implementation of the DendroBLAST method is freely available for use at http://www.dendroblast.com/.

BlockLogo: visualization of peptide and sequence motif conservation

PubMed Central

Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian; Sun, Jing; Schönbach, Christian; Reinherz, Ellis L.; Zhang, Guang Lan; Brusic, Vladimir

2013-01-01

BlockLogo is a web-server application for visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://methilab.bu.edu/blocklogo/ PMID:24001880

Multiple DNA and protein sequence alignment on a workstation and a supercomputer.

PubMed

Tajima, K

1988-11-01

This paper describes a multiple alignment method using a workstation and supercomputer. The method is based on the alignment of a set of aligned sequences with the new sequence, and uses a recursive procedure of such alignment. The alignment is executed in a reasonable computation time on diverse levels from a workstation to a supercomputer, from the viewpoint of alignment results and computational speed by parallel processing. The application of the algorithm is illustrated by several examples of multiple alignment of 12 amino acid and DNA sequences of HIV (human immunodeficiency virus) env genes. Colour graphic programs on a workstation and parallel processing on a supercomputer are discussed.

Electrospun fibrinogen-PLA nanofibres for vascular tissue engineering.

PubMed

Gugutkov, D; Gustavsson, J; Cantini, M; Salmeron-Sánchez, M; Altankov, G

2017-10-01

Here we report on the development of a new type of hybrid fibrinogen-polylactic acid (FBG-PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate-like morphology with multiple projections. The well-developed focal adhesion complexes suggested a successful cellular interaction. However, time-lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time-lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Homeotropic alignment of multiple bent-core liquid crystal phases using a polydimethylsiloxane alignment layer

NASA Astrophysics Data System (ADS)

Carlson, Eric D.; Foley, Lee M.; Guzman, Edward; Korblova, Eva D.; Visvanathan, Rayshan; Ryu, SeongHo; Gim, Min-Jun; Tuchband, Michael R.; Yoon, Dong Ki; Clark, Noel A.; Walba, David M.

2017-08-01

The control of the molecular orientation of liquid crystals (LCs) is important in both understanding phase properties and the continuing development of new LC technologies including displays, organic transistors, and electro-optic devices. Many techniques have been developed for successfully inducing alignment of calamitic LCs, though these techniques typically do not translate to the alignment of bent-core liquid crystals (BCLCs). Some techniques have been utilized to align various phases of BCLCs, but these techniques are often unsuccessful for general alignment of multiple materials and/or multiple phases. Here, we demonstrate that glass cells treated with polydimethylsiloxane (PDMS) thin films induce high quality homeotropic alignment of multiple mesophases of four BCLCs. On cooling to the lowest temperature phase the homeotropic alignment is lost, and spherulitic growth is seen in crystal and crystal-like phases including the dark conglomerate (DC) and helical nanofilament (HNF) phases. Evidence of homeotropic alignment is observed using polarized optical microscopy. We speculate that the methyl groups on the surface of the PDMS films strongly interact with the aliphatic tails of each mesogens, resulting in homeotropic alignment.

Implied alignment: a synapomorphy-based multiple-sequence alignment method and its use in cladogram search

NASA Technical Reports Server (NTRS)

Wheeler, Ward C.

2003-01-01

A method to align sequence data based on parsimonious synapomorphy schemes generated by direct optimization (DO; earlier termed optimization alignment) is proposed. DO directly diagnoses sequence data on cladograms without an intervening multiple-alignment step, thereby creating topology-specific, dynamic homology statements. Hence, no multiple-alignment is required to generate cladograms. Unlike general and globally optimal multiple-alignment procedures, the method described here, implied alignment (IA), takes these dynamic homologies and traces them back through a single cladogram, linking the unaligned sequence positions in the terminal taxa via DO transformation series. These "lines of correspondence" link ancestor-descendent states and, when displayed as linearly arrayed columns without hypothetical ancestors, are largely indistinguishable from standard multiple alignment. Since this method is based on synapomorphy, the treatment of certain classes of insertion-deletion (indel) events may be different from that of other alignment procedures. As with all alignment methods, results are dependent on parameter assumptions such as indel cost and transversion:transition ratios. Such an IA could be used as a basis for phylogenetic search, but this would be questionable since the homologies derived from the implied alignment depend on its natal cladogram and any variance, between DO and IA + Search, due to heuristic approach. The utility of this procedure in heuristic cladogram searches using DO and the improvement of heuristic cladogram cost calculations are discussed. c2003 The Willi Hennig Society. Published by Elsevier Science (USA). All rights reserved.

KinView: A visual comparative sequence analysis tool for integrated kinome research

PubMed Central

McSkimming, Daniel Ian; Dastgheib, Shima; Baffi, Timothy R.; Byrne, Dominic P.; Ferries, Samantha; Scott, Steven Thomas; Newton, Alexandra C.; Eyers, Claire E.; Kochut, Krzysztof J.; Eyers, Patrick A.

2017-01-01

Multiple sequence alignments (MSAs) are a fundamental analysis tool used throughout biology to investigate relationships between protein sequence, structure, function, evolutionary history, and patterns of disease-associated variants. However, their widespread application in systems biology research is currently hindered by the lack of user-friendly tools to simultaneously visualize, manipulate and query the information conceptualized in large sequence alignments, and the challenges in integrating MSAs with multiple orthogonal data such as cancer variants and post-translational modifications, which are often stored in heterogeneous data sources and formats. Here, we present the Multiple Sequence Alignment Ontology (MSAOnt), which represents a profile or consensus alignment in an ontological format. Subsets of the alignment are easily selected through the SPARQL Protocol and RDF Query Language for downstream statistical analysis or visualization. We have also created the Kinome Viewer (KinView), an interactive integrative visualization that places eukaryotic protein kinase cancer variants in the context of natural sequence variation and experimentally determined post-translational modifications, which play central roles in the regulation of cellular signaling pathways. Using KinView, we identified differential phosphorylation patterns between tyrosine and serine/threonine kinases in the activation segment, a major kinase regulatory region that is often mutated in proliferative diseases. We discuss cancer variants that disrupt phosphorylation sites in the activation segment, and show how KinView can be used as a comparative tool to identify differences and similarities in natural variation, cancer variants and post-translational modifications between kinase groups, families and subfamilies. Based on KinView comparisons, we identify and experimentally characterize a regulatory tyrosine (Y177PLK4) in the PLK4 C-terminal activation segment region termed the P+1 loop. To further demonstrate the application of KinView in hypothesis generation and testing, we formulate and validate a hypothesis explaining a novel predicted loss-of-function variant (D523NPKCβ) in the regulatory spine of PKCβ, a recently identified tumor suppressor kinase. KinView provides a novel, extensible interface for performing comparative analyses between subsets of kinases and for integrating multiple types of residue specific annotations in user friendly formats. PMID:27731453

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

PubMed

Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

2017-04-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

Accurate multiple sequence-structure alignment of RNA sequences using combinatorial optimization.

PubMed

Bauer, Markus; Klau, Gunnar W; Reinert, Knut

2007-07-27

The discovery of functional non-coding RNA sequences has led to an increasing interest in algorithms related to RNA analysis. Traditional sequence alignment algorithms, however, fail at computing reliable alignments of low-homology RNA sequences. The spatial conformation of RNA sequences largely determines their function, and therefore RNA alignment algorithms have to take structural information into account. We present a graph-based representation for sequence-structure alignments, which we model as an integer linear program (ILP). We sketch how we compute an optimal or near-optimal solution to the ILP using methods from combinatorial optimization, and present results on a recently published benchmark set for RNA alignments. The implementation of our algorithm yields better alignments in terms of two published scores than the other programs that we tested: This is especially the case with an increasing number of input sequences. Our program LARA is freely available for academic purposes from http://www.planet-lisa.net.

The Application of the Weighted k-Partite Graph Problem to the Multiple Alignment for Metabolic Pathways.

PubMed

Chen, Wenbin; Hendrix, William; Samatova, Nagiza F

2017-12-01

The problem of aligning multiple metabolic pathways is one of very challenging problems in computational biology. A metabolic pathway consists of three types of entities: reactions, compounds, and enzymes. Based on similarities between enzymes, Tohsato et al. gave an algorithm for aligning multiple metabolic pathways. However, the algorithm given by Tohsato et al. neglects the similarities among reactions, compounds, enzymes, and pathway topology. How to design algorithms for the alignment problem of multiple metabolic pathways based on the similarity of reactions, compounds, and enzymes? It is a difficult computational problem. In this article, we propose an algorithm for the problem of aligning multiple metabolic pathways based on the similarities among reactions, compounds, enzymes, and pathway topology. First, we compute a weight between each pair of like entities in different input pathways based on the entities' similarity score and topological structure using Ay et al.'s methods. We then construct a weighted k-partite graph for the reactions, compounds, and enzymes. We extract a mapping between these entities by solving the maximum-weighted k-partite matching problem by applying a novel heuristic algorithm. By analyzing the alignment results of multiple pathways in different organisms, we show that the alignments found by our algorithm correctly identify common subnetworks among multiple pathways.

MICA: Multiple interval-based curve alignment

NASA Astrophysics Data System (ADS)

Mann, Martin; Kahle, Hans-Peter; Beck, Matthias; Bender, Bela Johannes; Spiecker, Heinrich; Backofen, Rolf

2018-01-01

MICA enables the automatic synchronization of discrete data curves. To this end, characteristic points of the curves' shapes are identified. These landmarks are used within a heuristic curve registration approach to align profile pairs by mapping similar characteristics onto each other. In combination with a progressive alignment scheme, this enables the computation of multiple curve alignments. Multiple curve alignments are needed to derive meaningful representative consensus data of measured time or data series. MICA was already successfully applied to generate representative profiles of tree growth data based on intra-annual wood density profiles or cell formation data. The MICA package provides a command-line and graphical user interface. The R interface enables the direct embedding of multiple curve alignment computation into larger analyses pipelines. Source code, binaries and documentation are freely available at https://github.com/BackofenLab/MICA

Mango: multiple alignment with N gapped oligos.

PubMed

Zhang, Zefeng; Lin, Hao; Li, Ming

2008-06-01

Multiple sequence alignment is a classical and challenging task. The problem is NP-hard. The full dynamic programming takes too much time. The progressive alignment heuristics adopted by most state-of-the-art works suffer from the "once a gap, always a gap" phenomenon. Is there a radically new way to do multiple sequence alignment? In this paper, we introduce a novel and orthogonal multiple sequence alignment method, using both multiple optimized spaced seeds and new algorithms to handle these seeds efficiently. Our new algorithm processes information of all sequences as a whole and tries to build the alignment vertically, avoiding problems caused by the popular progressive approaches. Because the optimized spaced seeds have proved significantly more sensitive than the consecutive k-mers, the new approach promises to be more accurate and reliable. To validate our new approach, we have implemented MANGO: Multiple Alignment with N Gapped Oligos. Experiments were carried out on large 16S RNA benchmarks, showing that MANGO compares favorably, in both accuracy and speed, against state-of-the-art multiple sequence alignment methods, including ClustalW 1.83, MUSCLE 3.6, MAFFT 5.861, ProbConsRNA 1.11, Dialign 2.2.1, DIALIGN-T 0.2.1, T-Coffee 4.85, POA 2.0, and Kalign 2.0. We have further demonstrated the scalability of MANGO on very large datasets of repeat elements. MANGO can be downloaded at http://www.bioinfo.org.cn/mango/ and is free for academic usage.

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer

PubMed Central

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L.

2016-01-01

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. PMID:26590264

DNA Multiple Sequence Alignment Guided by Protein Domains: The MSA-PAD 2.0 Method.

PubMed

Balech, Bachir; Monaco, Alfonso; Perniola, Michele; Santamaria, Monica; Donvito, Giacinto; Vicario, Saverio; Maggi, Giorgio; Pesole, Graziano

2018-01-01

Multiple sequence alignment (MSA) is a fundamental component in many DNA sequence analyses including metagenomics studies and phylogeny inference. When guided by protein profiles, DNA multiple alignments assume a higher precision and robustness. Here we present details of the use of the upgraded version of MSA-PAD (2.0), which is a DNA multiple sequence alignment framework able to align DNA sequences coding for single/multiple protein domains guided by PFAM or user-defined annotations. MSA-PAD has two alignment strategies, called "Gene" and "Genome," accounting for coding domains order and genomic rearrangements, respectively. Novel options were added to the present version, where the MSA can be guided by protein profiles provided by the user. This allows MSA-PAD 2.0 to run faster and to add custom protein profiles sometimes not present in PFAM database according to the user's interest. MSA-PAD 2.0 is currently freely available as a Web application at https://recasgateway.cloud.ba.infn.it/ .

Score distributions of gapped multiple sequence alignments down to the low-probability tail

NASA Astrophysics Data System (ADS)

Fieth, Pascal; Hartmann, Alexander K.

2016-08-01

Assessing the significance of alignment scores of optimally aligned DNA or amino acid sequences can be achieved via the knowledge of the score distribution of random sequences. But this requires obtaining the distribution in the biologically relevant high-scoring region, where the probabilities are exponentially small. For gapless local alignments of infinitely long sequences this distribution is known analytically to follow a Gumbel distribution. Distributions for gapped local alignments and global alignments of finite lengths can only be obtained numerically. To obtain result for the small-probability region, specific statistical mechanics-based rare-event algorithms can be applied. In previous studies, this was achieved for pairwise alignments. They showed that, contrary to results from previous simple sampling studies, strong deviations from the Gumbel distribution occur in case of finite sequence lengths. Here we extend the studies to multiple sequence alignments with gaps, which are much more relevant for practical applications in molecular biology. We study the distributions of scores over a large range of the support, reaching probabilities as small as 10-160, for global and local (sum-of-pair scores) multiple alignments. We find that even after suitable rescaling, eliminating the sequence-length dependence, the distributions for multiple alignment differ from the pairwise alignment case. Furthermore, we also show that the previously discussed Gaussian correction to the Gumbel distribution needs to be refined, also for the case of pairwise alignments.

TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics.

PubMed

Röst, Hannes L; Liu, Yansheng; D'Agostino, Giuseppe; Zanella, Matteo; Navarro, Pedro; Rosenberger, George; Collins, Ben C; Gillet, Ludovic; Testa, Giuseppe; Malmström, Lars; Aebersold, Ruedi

2016-09-01

Next-generation mass spectrometric (MS) techniques such as SWATH-MS have substantially increased the throughput and reproducibility of proteomic analysis, but ensuring consistent quantification of thousands of peptide analytes across multiple liquid chromatography-tandem MS (LC-MS/MS) runs remains a challenging and laborious manual process. To produce highly consistent and quantitatively accurate proteomics data matrices in an automated fashion, we developed TRIC (http://proteomics.ethz.ch/tric/), a software tool that utilizes fragment-ion data to perform cross-run alignment, consistent peak-picking and quantification for high-throughput targeted proteomics. TRIC reduced the identification error compared to a state-of-the-art SWATH-MS analysis without alignment by more than threefold at constant recall while correcting for highly nonlinear chromatographic effects. On a pulsed-SILAC experiment performed on human induced pluripotent stem cells, TRIC was able to automatically align and quantify thousands of light and heavy isotopic peak groups. Thus, TRIC fills a gap in the pipeline for automated analysis of massively parallel targeted proteomics data sets.

A Novel Center Star Multiple Sequence Alignment Algorithm Based on Affine Gap Penalty and K-Band

NASA Astrophysics Data System (ADS)

Zou, Quan; Shan, Xiao; Jiang, Yi

Multiple sequence alignment is one of the most important topics in computational biology, but it cannot deal with the large data so far. As the development of copy-number variant(CNV) and Single Nucleotide Polymorphisms(SNP) research, many researchers want to align numbers of similar sequences for detecting CNV and SNP. In this paper, we propose a novel multiple sequence alignment algorithm based on affine gap penalty and k-band. It can align more quickly and accurately, that will be helpful for mining CNV and SNP. Experiments prove the performance of our algorithm.

Phylogenetic study of Class Armophorea (Alveolata, Ciliophora) based on 18S-rDNA data.

PubMed

da Silva Paiva, Thiago; do Nascimento Borges, Bárbara; da Silva-Neto, Inácio Domingos

2013-12-01

The 18S rDNA phylogeny of Class Armophorea, a group of anaerobic ciliates, is proposed based on an analysis of 44 sequences (out of 195) retrieved from the NCBI/GenBank database. Emphasis was placed on the use of two nucleotide alignment criteria that involved variation in the gap-opening and gap-extension parameters and the use of rRNA secondary structure to orientate multiple-alignment. A sensitivity analysis of 76 data sets was run to assess the effect of variations in indel parameters on tree topologies. Bayesian inference, maximum likelihood and maximum parsimony phylogenetic analyses were used to explore how different analytic frameworks influenced the resulting hypotheses. A sensitivity analysis revealed that the relationships among higher taxa of the Intramacronucleata were dependent upon how indels were determined during multiple-alignment of nucleotides. The phylogenetic analyses rejected the monophyly of the Armophorea most of the time and consistently indicated that the Metopidae and Nyctotheridae were related to the Litostomatea. There was no consensus on the placement of the Caenomorphidae, which could be a sister group of the Metopidae + Nyctorheridae, or could have diverged at the base of the Spirotrichea branch or the Intramacronucleata tree.

Phylogenetic study of Class Armophorea (Alveolata, Ciliophora) based on 18S-rDNA data

PubMed Central

da Silva Paiva, Thiago; do Nascimento Borges, Bárbara; da Silva-Neto, Inácio Domingos

2013-01-01

The 18S rDNA phylogeny of Class Armophorea, a group of anaerobic ciliates, is proposed based on an analysis of 44 sequences (out of 195) retrieved from the NCBI/GenBank database. Emphasis was placed on the use of two nucleotide alignment criteria that involved variation in the gap-opening and gap-extension parameters and the use of rRNA secondary structure to orientate multiple-alignment. A sensitivity analysis of 76 data sets was run to assess the effect of variations in indel parameters on tree topologies. Bayesian inference, maximum likelihood and maximum parsimony phylogenetic analyses were used to explore how different analytic frameworks influenced the resulting hypotheses. A sensitivity analysis revealed that the relationships among higher taxa of the Intramacronucleata were dependent upon how indels were determined during multiple-alignment of nucleotides. The phylogenetic analyses rejected the monophyly of the Armophorea most of the time and consistently indicated that the Metopidae and Nyctotheridae were related to the Litostomatea. There was no consensus on the placement of the Caenomorphidae, which could be a sister group of the Metopidae + Nyctorheridae, or could have diverged at the base of the Spirotrichea branch or the Intramacronucleata tree. PMID:24385862

SINA: accurate high-throughput multiple sequence alignment of ribosomal RNA genes.

PubMed

Pruesse, Elmar; Peplies, Jörg; Glöckner, Frank Oliver

2012-07-15

In the analysis of homologous sequences, computation of multiple sequence alignments (MSAs) has become a bottleneck. This is especially troublesome for marker genes like the ribosomal RNA (rRNA) where already millions of sequences are publicly available and individual studies can easily produce hundreds of thousands of new sequences. Methods have been developed to cope with such numbers, but further improvements are needed to meet accuracy requirements. In this study, we present the SILVA Incremental Aligner (SINA) used to align the rRNA gene databases provided by the SILVA ribosomal RNA project. SINA uses a combination of k-mer searching and partial order alignment (POA) to maintain very high alignment accuracy while satisfying high throughput performance demands. SINA was evaluated in comparison with the commonly used high throughput MSA programs PyNAST and mothur. The three BRAliBase III benchmark MSAs could be reproduced with 99.3, 97.6 and 96.1 accuracy. A larger benchmark MSA comprising 38 772 sequences could be reproduced with 98.9 and 99.3% accuracy using reference MSAs comprising 1000 and 5000 sequences. SINA was able to achieve higher accuracy than PyNAST and mothur in all performed benchmarks. Alignment of up to 500 sequences using the latest SILVA SSU/LSU Ref datasets as reference MSA is offered at http://www.arb-silva.de/aligner. This page also links to Linux binaries, user manual and tutorial. SINA is made available under a personal use license.

DIALIGN P: fast pair-wise and multiple sequence alignment using parallel processors.

PubMed

Schmollinger, Martin; Nieselt, Kay; Kaufmann, Michael; Morgenstern, Burkhard

2004-09-09

Parallel computing is frequently used to speed up computationally expensive tasks in Bioinformatics. Herein, a parallel version of the multi-alignment program DIALIGN is introduced. We propose two ways of dividing the program into independent sub-routines that can be run on different processors: (a) pair-wise sequence alignments that are used as a first step to multiple alignment account for most of the CPU time in DIALIGN. Since alignments of different sequence pairs are completely independent of each other, they can be distributed to multiple processors without any effect on the resulting output alignments. (b) For alignments of large genomic sequences, we use a heuristics by splitting up sequences into sub-sequences based on a previously introduced anchored alignment procedure. For our test sequences, this combined approach reduces the program running time of DIALIGN by up to 97%. By distributing sub-routines to multiple processors, the running time of DIALIGN can be crucially improved. With these improvements, it is possible to apply the program in large-scale genomics and proteomics projects that were previously beyond its scope.

RNA-TVcurve: a Web server for RNA secondary structure comparison based on a multi-scale similarity of its triple vector curve representation.

PubMed

Li, Ying; Shi, Xiaohu; Liang, Yanchun; Xie, Juan; Zhang, Yu; Ma, Qin

2017-01-21

RNAs have been found to carry diverse functionalities in nature. Inferring the similarity between two given RNAs is a fundamental step to understand and interpret their functional relationship. The majority of functional RNAs show conserved secondary structures, rather than sequence conservation. Those algorithms relying on sequence-based features usually have limitations in their prediction performance. Hence, integrating RNA structure features is very critical for RNA analysis. Existing algorithms mainly fall into two categories: alignment-based and alignment-free. The alignment-free algorithms of RNA comparison usually have lower time complexity than alignment-based algorithms. An alignment-free RNA comparison algorithm was proposed, in which novel numerical representations RNA-TVcurve (triple vector curve representation) of RNA sequence and corresponding secondary structure features are provided. Then a multi-scale similarity score of two given RNAs was designed based on wavelet decomposition of their numerical representation. In support of RNA mutation and phylogenetic analysis, a web server (RNA-TVcurve) was designed based on this alignment-free RNA comparison algorithm. It provides three functional modules: 1) visualization of numerical representation of RNA secondary structure; 2) detection of single-point mutation based on secondary structure; and 3) comparison of pairwise and multiple RNA secondary structures. The inputs of the web server require RNA primary sequences, while corresponding secondary structures are optional. For the primary sequences alone, the web server can compute the secondary structures using free energy minimization algorithm in terms of RNAfold tool from Vienna RNA package. RNA-TVcurve is the first integrated web server, based on an alignment-free method, to deliver a suite of RNA analysis functions, including visualization, mutation analysis and multiple RNAs structure comparison. The comparison results with two popular RNA comparison tools, RNApdist and RNAdistance, showcased that RNA-TVcurve can efficiently capture subtle relationships among RNAs for mutation detection and non-coding RNA classification. All the relevant results were shown in an intuitive graphical manner, and can be freely downloaded from this server. RNA-TVcurve, along with test examples and detailed documents, are available at: http://ml.jlu.edu.cn/tvcurve/ .

The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes.

PubMed

Treangen, Todd J; Ondov, Brian D; Koren, Sergey; Phillippy, Adam M

2014-01-01

Whole-genome sequences are now available for many microbial species and clades, however existing whole-genome alignment methods are limited in their ability to perform sequence comparisons of multiple sequences simultaneously. Here we present the Harvest suite of core-genome alignment and visualization tools for the rapid and simultaneous analysis of thousands of intraspecific microbial strains. Harvest includes Parsnp, a fast core-genome multi-aligner, and Gingr, a dynamic visual platform. Together they provide interactive core-genome alignments, variant calls, recombination detection, and phylogenetic trees. Using simulated and real data we demonstrate that our approach exhibits unrivaled speed while maintaining the accuracy of existing methods. The Harvest suite is open-source and freely available from: http://github.com/marbl/harvest.

Alignment of learning objectives and assessments in therapeutics courses to foster higher-order thinking.

PubMed

FitzPatrick, Beverly; Hawboldt, John; Doyle, Daniel; Genge, Terri

2015-02-17

To determine whether national educational outcomes, course objectives, and classroom assessments for 2 therapeutics courses were aligned for curricular content and cognitive processes, and if they included higher-order thinking. Document analysis and student focus groups were used. Outcomes, objectives, and assessment tasks were matched for specific therapeutics content and cognitive processes. Anderson and Krathwohl's Taxonomy was used to define higher-order thinking. Students discussed whether assessments tested objectives and described their thinking when responding to assessments. There were 7 outcomes, 31 objectives, and 412 assessment tasks. The alignment for content and cognitive processes was not satisfactory. Twelve students participated in the focus groups. Students thought more short-answer questions than multiple choice questions matched the objectives for content and required higher-order thinking. The alignment analysis provided data that could be used to reveal and strengthen the enacted curriculum and improve student learning.

Matt: local flexibility aids protein multiple structure alignment.

PubMed

Menke, Matthew; Berger, Bonnie; Cowen, Lenore

2008-01-01

Even when there is agreement on what measure a protein multiple structure alignment should be optimizing, finding the optimal alignment is computationally prohibitive. One approach used by many previous methods is aligned fragment pair chaining, where short structural fragments from all the proteins are aligned against each other optimally, and the final alignment chains these together in geometrically consistent ways. Ye and Godzik have recently suggested that adding geometric flexibility may help better model protein structures in a variety of contexts. We introduce the program Matt (Multiple Alignment with Translations and Twists), an aligned fragment pair chaining algorithm that, in intermediate steps, allows local flexibility between fragments: small translations and rotations are temporarily allowed to bring sets of aligned fragments closer, even if they are physically impossible under rigid body transformations. After a dynamic programming assembly guided by these "bent" alignments, geometric consistency is restored in the final step before the alignment is output. Matt is tested against other recent multiple protein structure alignment programs on the popular Homstrad and SABmark benchmark datasets. Matt's global performance is competitive with the other programs on Homstrad, but outperforms the other programs on SABmark, a benchmark of multiple structure alignments of proteins with more distant homology. On both datasets, Matt demonstrates an ability to better align the ends of alpha-helices and beta-strands, an important characteristic of any structure alignment program intended to help construct a structural template library for threading approaches to the inverse protein-folding problem. The related question of whether Matt alignments can be used to distinguish distantly homologous structure pairs from pairs of proteins that are not homologous is also considered. For this purpose, a p-value score based on the length of the common core and average root mean squared deviation (RMSD) of Matt alignments is shown to largely separate decoys from homologous protein structures in the SABmark benchmark dataset. We postulate that Matt's strong performance comes from its ability to model proteins in different conformational states and, perhaps even more important, its ability to model backbone distortions in more distantly related proteins.

Image Alignment for Multiple Camera High Dynamic Range Microscopy.

PubMed

Eastwood, Brian S; Childs, Elisabeth C

2012-01-09

This paper investigates the problem of image alignment for multiple camera high dynamic range (HDR) imaging. HDR imaging combines information from images taken with different exposure settings. Combining information from multiple cameras requires an alignment process that is robust to the intensity differences in the images. HDR applications that use a limited number of component images require an alignment technique that is robust to large exposure differences. We evaluate the suitability for HDR alignment of three exposure-robust techniques. We conclude that image alignment based on matching feature descriptors extracted from radiant power images from calibrated cameras yields the most accurate and robust solution. We demonstrate the use of this alignment technique in a high dynamic range video microscope that enables live specimen imaging with a greater level of detail than can be captured with a single camera.

Image Alignment for Multiple Camera High Dynamic Range Microscopy

PubMed Central

Eastwood, Brian S.; Childs, Elisabeth C.

2012-01-01

This paper investigates the problem of image alignment for multiple camera high dynamic range (HDR) imaging. HDR imaging combines information from images taken with different exposure settings. Combining information from multiple cameras requires an alignment process that is robust to the intensity differences in the images. HDR applications that use a limited number of component images require an alignment technique that is robust to large exposure differences. We evaluate the suitability for HDR alignment of three exposure-robust techniques. We conclude that image alignment based on matching feature descriptors extracted from radiant power images from calibrated cameras yields the most accurate and robust solution. We demonstrate the use of this alignment technique in a high dynamic range video microscope that enables live specimen imaging with a greater level of detail than can be captured with a single camera. PMID:22545028

Embedding strategies for effective use of information from multiple sequence alignments.

PubMed Central

Henikoff, S.; Henikoff, J. G.

1997-01-01

We describe a new strategy for utilizing multiple sequence alignment information to detect distant relationships in searches of sequence databases. A single sequence representing a protein family is enriched by replacing conserved regions with position-specific scoring matrices (PSSMs) or consensus residues derived from multiple alignments of family members. In comprehensive tests of these and other family representations, PSSM-embedded queries produced the best results overall when used with a special version of the Smith-Waterman searching algorithm. Moreover, embedding consensus residues instead of PSSMs improved performance with readily available single sequence query searching programs, such as BLAST and FASTA. Embedding PSSMs or consensus residues into a representative sequence improves searching performance by extracting multiple alignment information from motif regions while retaining single sequence information where alignment is uncertain. PMID:9070452

Association of low back pain with muscle stiffness and muscle mass of the lumbar back muscles, and sagittal spinal alignment in young and middle-aged medical workers.

PubMed

Masaki, Mitsuhiro; Aoyama, Tomoki; Murakami, Takashi; Yanase, Ko; Ji, Xiang; Tateuchi, Hiroshige; Ichihashi, Noriaki

2017-11-01

Muscle stiffness of the lumbar back muscles in low back pain (LBP) patients has not been clearly elucidated because quantitative assessment of the stiffness of individual muscles was conventionally difficult. This study aimed to examine the association of LBP with muscle stiffness assessed using ultrasonic shear wave elastography (SWE) and muscle mass of the lumbar back muscle, and spinal alignment in young and middle-aged medical workers. The study comprised 23 asymptomatic medical workers [control (CTR) group] and 9 medical workers with LBP (LBP group). Muscle stiffness and mass of the lumbar back muscles (lumbar erector spinae, multifidus, and quadratus lumborum) in the prone position were measured using ultrasonic SWE. Sagittal spinal alignment in the standing and prone positions was measured using a Spinal Mouse. The association with LBP was investigated by multiple logistic regression analysis with a forward selection method. The analysis was conducted using the shear elastic modulus and muscle thickness of the lumbar back muscles, and spinal alignment, age, body height, body weight, and sex as independent variables. Multiple logistic regression analysis showed that muscle stiffness of the lumbar multifidus muscle and body height were significant and independent determinants of LBP, but that muscle mass and spinal alignment were not. Muscle stiffness of the lumbar multifidus muscle in the LBP group was significantly higher than that in the CTR group. The results of this study suggest that LBP is associated with muscle stiffness of the lumbar multifidus muscle in young and middle-aged medical workers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

NASA Astrophysics Data System (ADS)

Cornelissen, Frans; De Backer, Steve; Lemeire, Jan; Torfs, Berf; Nuydens, Rony; Meert, Theo; Schelkens, Peter; Scheunders, Paul

2008-08-01

Peripheral neuropathy can be caused by diabetes or AIDS or be a side-effect of chemotherapy. Fibered Fluorescence Microscopy (FFM) is a recently developed imaging modality using a fiber optic probe connected to a laser scanning unit. It allows for in-vivo scanning of small animal subjects by moving the probe along the tissue surface. In preclinical research, FFM enables non-invasive, longitudinal in vivo assessment of intra epidermal nerve fibre density in various models for peripheral neuropathies. By moving the probe, FFM allows visualization of larger surfaces, since, during the movement, images are continuously captured, allowing to acquire an area larger then the field of view of the probe. For analysis purposes, we need to obtain a single static image from the multiple overlapping frames. We introduce a mosaicing procedure for this kind of video sequence. Construction of mosaic images with sub-pixel alignment is indispensable and must be integrated into a global consistent image aligning. An additional motivation for the mosaicing is the use of overlapping redundant information to improve the signal to noise ratio of the acquisition, because the individual frames tend to have both high noise levels and intensity inhomogeneities. For longitudinal analysis, mosaics captured at different times must be aligned as well. For alignment, global correlation-based matching is compared with interest point matching. Use of algorithms working on multiple CPU's (parallel processor/cluster/grid) is imperative for use in a screening model.

Reconstructing evolutionary trees in parallel for massive sequences.

PubMed

Zou, Quan; Wan, Shixiang; Zeng, Xiangxiang; Ma, Zhanshan Sam

2017-12-14

Building the evolutionary trees for massive unaligned DNA sequences is challenging and crucial. However, reconstructing evolutionary tree for ultra-large sequences is hard. Massive multiple sequence alignment is also challenging and time/space consuming. Hadoop and Spark are developed recently, which bring spring light for the classical computational biology problems. In this paper, we tried to solve the multiple sequence alignment and evolutionary reconstruction in parallel. HPTree, which is developed in this paper, can deal with big DNA sequence files quickly. It works well on the >1GB files, and gets better performance than other evolutionary reconstruction tools. Users could use HPTree for reonstructing evolutioanry trees on the computer clusters or cloud platform (eg. Amazon Cloud). HPTree could help on population evolution research and metagenomics analysis. In this paper, we employ the Hadoop and Spark platform and design an evolutionary tree reconstruction software tool for unaligned massive DNA sequences. Clustering and multiple sequence alignment are done in parallel. Neighbour-joining model was employed for the evolutionary tree building. We opened our software together with source codes via http://lab.malab.cn/soft/HPtree/ .

Using reconfigurable hardware to accelerate multiple sequence alignment with ClustalW.

PubMed

Oliver, Tim; Schmidt, Bertil; Nathan, Darran; Clemens, Ralf; Maskell, Douglas

2005-08-15

Aligning hundreds of sequences using progressive alignment tools such as ClustalW requires several hours on state-of-the-art workstations. We present a new approach to compute multiple sequence alignments in far shorter time using reconfigurable hardware. This results in an implementation of ClustalW with significant runtime savings on a standard off-the-shelf FPGA.

Sequence Diversity Diagram for comparative analysis of multiple sequence alignments.

PubMed

Sakai, Ryo; Aerts, Jan

2014-01-01

The sequence logo is a graphical representation of a set of aligned sequences, commonly used to depict conservation of amino acid or nucleotide sequences. Although it effectively communicates the amount of information present at every position, this visual representation falls short when the domain task is to compare between two or more sets of aligned sequences. We present a new visual presentation called a Sequence Diversity Diagram and validate our design choices with a case study. Our software was developed using the open-source program called Processing. It loads multiple sequence alignment FASTA files and a configuration file, which can be modified as needed to change the visualization. The redesigned figure improves on the visual comparison of two or more sets, and it additionally encodes information on sequential position conservation. In our case study of the adenylate kinase lid domain, the Sequence Diversity Diagram reveals unexpected patterns and new insights, for example the identification of subgroups within the protein subfamily. Our future work will integrate this visual encoding into interactive visualization tools to support higher level data exploration tasks.

CMSA: a heterogeneous CPU/GPU computing system for multiple similar RNA/DNA sequence alignment.

PubMed

Chen, Xi; Wang, Chen; Tang, Shanjiang; Yu, Ce; Zou, Quan

2017-06-24

The multiple sequence alignment (MSA) is a classic and powerful technique for sequence analysis in bioinformatics. With the rapid growth of biological datasets, MSA parallelization becomes necessary to keep its running time in an acceptable level. Although there are a lot of work on MSA problems, their approaches are either insufficient or contain some implicit assumptions that limit the generality of usage. First, the information of users' sequences, including the sizes of datasets and the lengths of sequences, can be of arbitrary values and are generally unknown before submitted, which are unfortunately ignored by previous work. Second, the center star strategy is suited for aligning similar sequences. But its first stage, center sequence selection, is highly time-consuming and requires further optimization. Moreover, given the heterogeneous CPU/GPU platform, prior studies consider the MSA parallelization on GPU devices only, making the CPUs idle during the computation. Co-run computation, however, can maximize the utilization of the computing resources by enabling the workload computation on both CPU and GPU simultaneously. This paper presents CMSA, a robust and efficient MSA system for large-scale datasets on the heterogeneous CPU/GPU platform. It performs and optimizes multiple sequence alignment automatically for users' submitted sequences without any assumptions. CMSA adopts the co-run computation model so that both CPU and GPU devices are fully utilized. Moreover, CMSA proposes an improved center star strategy that reduces the time complexity of its center sequence selection process from O(mn 2 ) to O(mn). The experimental results show that CMSA achieves an up to 11× speedup and outperforms the state-of-the-art software. CMSA focuses on the multiple similar RNA/DNA sequence alignment and proposes a novel bitmap based algorithm to improve the center star strategy. We can conclude that harvesting the high performance of modern GPU is a promising approach to accelerate multiple sequence alignment. Besides, adopting the co-run computation model can maximize the entire system utilization significantly. The source code is available at https://github.com/wangvsa/CMSA .

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer.

PubMed

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L

2016-01-04

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences.

PubMed

Bonizzoni, Paola; Rizzi, Raffaella; Pesole, Graziano

2005-10-05

Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems--hence the need to develop novel strategies. We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations. We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility. Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at http://aspic.algo.disco.unimib.it/aspic-devel/.

Kernel-aligned multi-view canonical correlation analysis for image recognition

NASA Astrophysics Data System (ADS)

Su, Shuzhi; Ge, Hongwei; Yuan, Yun-Hao

2016-09-01

Existing kernel-based correlation analysis methods mainly adopt a single kernel in each view. However, only a single kernel is usually insufficient to characterize nonlinear distribution information of a view. To solve the problem, we transform each original feature vector into a 2-dimensional feature matrix by means of kernel alignment, and then propose a novel kernel-aligned multi-view canonical correlation analysis (KAMCCA) method on the basis of the feature matrices. Our proposed method can simultaneously employ multiple kernels to better capture the nonlinear distribution information of each view, so that correlation features learned by KAMCCA can have well discriminating power in real-world image recognition. Extensive experiments are designed on five real-world image datasets, including NIR face images, thermal face images, visible face images, handwritten digit images, and object images. Promising experimental results on the datasets have manifested the effectiveness of our proposed method.

TaxI: a software tool for DNA barcoding using distance methods

PubMed Central

Steinke, Dirk; Vences, Miguel; Salzburger, Walter; Meyer, Axel

2005-01-01

DNA barcoding is a promising approach to the diagnosis of biological diversity in which DNA sequences serve as the primary key for information retrieval. Most existing software for evolutionary analysis of DNA sequences was designed for phylogenetic analyses and, hence, those algorithms do not offer appropriate solutions for the rapid, but precise analyses needed for DNA barcoding, and are also unable to process the often large comparative datasets. We developed a flexible software tool for DNA taxonomy, named TaxI. This program calculates sequence divergences between a query sequence (taxon to be barcoded) and each sequence of a dataset of reference sequences defined by the user. Because the analysis is based on separate pairwise alignments this software is also able to work with sequences characterized by multiple insertions and deletions that are difficult to align in large sequence sets (i.e. thousands of sequences) by multiple alignment algorithms because of computational restrictions. Here, we demonstrate the utility of this approach with two datasets of fish larvae and juveniles from Lake Constance and juvenile land snails under different models of sequence evolution. Sets of ribosomal 16S rRNA sequences, characterized by multiple indels, performed as good as or better than cox1 sequence sets in assigning sequences to species, demonstrating the suitability of rRNA genes for DNA barcoding. PMID:16214755

Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model

PubMed Central

2010-01-01

Background The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes. Results In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV). Conclusions The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size. PMID:20565983

Simultaneous dual-color fluorescence microscope: a characterization study.

PubMed

Li, Zheng; Chen, Xiaodong; Ren, Liqiang; Song, Jie; Li, Yuhua; Zheng, Bin; Liu, Hong

2013-01-01

High spatial resolution and geometric accuracy is crucial for chromosomal analysis of clinical cytogenetic applications. High resolution and rapid simultaneous acquisition of multiple fluorescent wavelengths can be achieved by utilizing concurrent imaging with multiple detectors. However, such class of microscopic systems functions differently from traditional fluorescence microscopes. To develop a practical characterization framework to assess and optimize the performance of a high resolution and dual-color fluorescence microscope designed for clinical chromosomal analysis. A dual-band microscopic imaging system utilizes a dichroic mirror, two sets of specially selected optical filters, and two detectors to simultaneously acquire two fluorescent wavelengths. The system's geometric distortion, linearity, the modulation transfer function, and the dual detectors' alignment were characterized. Experiment results show that the geometric distortion at lens periphery is less than 1%. Both fluorescent channels show linear signal responses, but there exists discrepancy between the two due to the detectors' non-uniform response ratio to different wavelengths. In terms of the spatial resolution, the two contrast transfer function curves trend agreeably with the spatial frequency. The alignment measurement allows quantitatively assessing the cameras' alignment. A result image of adjusted alignment is demonstrated to show the reduced discrepancy by using the alignment measurement method. In this paper, we present a system characterization study and its methods for a specially designed imaging system for clinical cytogenetic applications. The presented characterization methods are not only unique to this dual-color imaging system but also applicable to evaluation and optimization of other similar multi-color microscopic image systems for improving their clinical utilities for future cytogenetic applications.

Hal: an automated pipeline for phylogenetic analyses of genomic data.

PubMed

Robbertse, Barbara; Yoder, Ryan J; Boyd, Alex; Reeves, John; Spatafora, Joseph W

2011-02-07

The rapid increase in genomic and genome-scale data is resulting in unprecedented levels of discrete sequence data available for phylogenetic analyses. Major analytical impasses exist, however, prior to analyzing these data with existing phylogenetic software. Obstacles include the management of large data sets without standardized naming conventions, identification and filtering of orthologous clusters of proteins or genes, and the assembly of alignments of orthologous sequence data into individual and concatenated super alignments. Here we report the production of an automated pipeline, Hal that produces multiple alignments and trees from genomic data. These alignments can be produced by a choice of four alignment programs and analyzed by a variety of phylogenetic programs. In short, the Hal pipeline connects the programs BLASTP, MCL, user specified alignment programs, GBlocks, ProtTest and user specified phylogenetic programs to produce species trees. The script is available at sourceforge (http://sourceforge.net/projects/bio-hal/). The results from an example analysis of Kingdom Fungi are briefly discussed.

Flexible, fast and accurate sequence alignment profiling on GPGPU with PaSWAS.

PubMed

Warris, Sven; Yalcin, Feyruz; Jackson, Katherine J L; Nap, Jan Peter

2015-01-01

To obtain large-scale sequence alignments in a fast and flexible way is an important step in the analyses of next generation sequencing data. Applications based on the Smith-Waterman (SW) algorithm are often either not fast enough, limited to dedicated tasks or not sufficiently accurate due to statistical issues. Current SW implementations that run on graphics hardware do not report the alignment details necessary for further analysis. With the Parallel SW Alignment Software (PaSWAS) it is possible (a) to have easy access to the computational power of NVIDIA-based general purpose graphics processing units (GPGPUs) to perform high-speed sequence alignments, and (b) retrieve relevant information such as score, number of gaps and mismatches. The software reports multiple hits per alignment. The added value of the new SW implementation is demonstrated with two test cases: (1) tag recovery in next generation sequence data and (2) isotype assignment within an immunoglobulin 454 sequence data set. Both cases show the usability and versatility of the new parallel Smith-Waterman implementation.

Sequence analysis by iterated maps, a review.

PubMed

Almeida, Jonas S

2014-05-01

Among alignment-free methods, Iterated Maps (IMs) are on a particular extreme: they are also scale free (order free). The use of IMs for sequence analysis is also distinct from other alignment-free methodologies in being rooted in statistical mechanics instead of computational linguistics. Both of these roots go back over two decades to the use of fractal geometry in the characterization of phase-space representations. The time series analysis origin of the field is betrayed by the title of the manuscript that started this alignment-free subdomain in 1990, 'Chaos Game Representation'. The clash between the analysis of sequences as continuous series and the better established use of Markovian approaches to discrete series was almost immediate, with a defining critique published in same journal 2 years later. The rest of that decade would go by before the scale-free nature of the IM space was uncovered. The ensuing decade saw this scalability generalized for non-genomic alphabets as well as an interest in its use for graphic representation of biological sequences. Finally, in the past couple of years, in step with the emergence of BigData and MapReduce as a new computational paradigm, there is a surprising third act in the IM story. Multiple reports have described gains in computational efficiency of multiple orders of magnitude over more conventional sequence analysis methodologies. The stage appears to be now set for a recasting of IMs with a central role in processing nextgen sequencing results.

PASTA: Ultra-Large Multiple Sequence Alignment for Nucleotide and Amino-Acid Sequences.

PubMed

Mirarab, Siavash; Nguyen, Nam; Guo, Sheng; Wang, Li-San; Kim, Junhyong; Warnow, Tandy

2015-05-01

We introduce PASTA, a new multiple sequence alignment algorithm. PASTA uses a new technique to produce an alignment given a guide tree that enables it to be both highly scalable and very accurate. We present a study on biological and simulated data with up to 200,000 sequences, showing that PASTA produces highly accurate alignments, improving on the accuracy and scalability of the leading alignment methods (including SATé). We also show that trees estimated on PASTA alignments are highly accurate--slightly better than SATé trees, but with substantial improvements relative to other methods. Finally, PASTA is faster than SATé, highly parallelizable, and requires relatively little memory.

Processing methods for differential analysis of LC/MS profile data

PubMed Central

Katajamaa, Mikko; Orešič, Matej

2005-01-01

Background Liquid chromatography coupled to mass spectrometry (LC/MS) has been widely used in proteomics and metabolomics research. In this context, the technology has been increasingly used for differential profiling, i.e. broad screening of biomolecular components across multiple samples in order to elucidate the observed phenotypes and discover biomarkers. One of the major challenges in this domain remains development of better solutions for processing of LC/MS data. Results We present a software package MZmine that enables differential LC/MS analysis of metabolomics data. This software is a toolbox containing methods for all data processing stages preceding differential analysis: spectral filtering, peak detection, alignment and normalization. Specifically, we developed and implemented a new recursive peak search algorithm and a secondary peak picking method for improving already aligned results, as well as a normalization tool that uses multiple internal standards. Visualization tools enable comparative viewing of data across multiple samples. Peak lists can be exported into other data analysis programs. The toolbox has already been utilized in a wide range of applications. We demonstrate its utility on an example of metabolic profiling of Catharanthus roseus cell cultures. Conclusion The software is freely available under the GNU General Public License and it can be obtained from the project web page at: . PMID:16026613

Processing methods for differential analysis of LC/MS profile data.

PubMed

Katajamaa, Mikko; Oresic, Matej

2005-07-18

Liquid chromatography coupled to mass spectrometry (LC/MS) has been widely used in proteomics and metabolomics research. In this context, the technology has been increasingly used for differential profiling, i.e. broad screening of biomolecular components across multiple samples in order to elucidate the observed phenotypes and discover biomarkers. One of the major challenges in this domain remains development of better solutions for processing of LC/MS data. We present a software package MZmine that enables differential LC/MS analysis of metabolomics data. This software is a toolbox containing methods for all data processing stages preceding differential analysis: spectral filtering, peak detection, alignment and normalization. Specifically, we developed and implemented a new recursive peak search algorithm and a secondary peak picking method for improving already aligned results, as well as a normalization tool that uses multiple internal standards. Visualization tools enable comparative viewing of data across multiple samples. Peak lists can be exported into other data analysis programs. The toolbox has already been utilized in a wide range of applications. We demonstrate its utility on an example of metabolic profiling of Catharanthus roseus cell cultures. The software is freely available under the GNU General Public License and it can be obtained from the project web page at: http://mzmine.sourceforge.net/.

Java bioinformatics analysis web services for multiple sequence alignment--JABAWS:MSA.

PubMed

Troshin, Peter V; Procter, James B; Barton, Geoffrey J

2011-07-15

JABAWS is a web services framework that simplifies the deployment of web services for bioinformatics. JABAWS:MSA provides services for five multiple sequence alignment (MSA) methods (Probcons, T-coffee, Muscle, Mafft and ClustalW), and is the system employed by the Jalview multiple sequence analysis workbench since version 2.6. A fully functional, easy to set up server is provided as a Virtual Appliance (VA), which can be run on most operating systems that support a virtualization environment such as VMware or Oracle VirtualBox. JABAWS is also distributed as a Web Application aRchive (WAR) and can be configured to run on a single computer and/or a cluster managed by Grid Engine, LSF or other queuing systems that support DRMAA. JABAWS:MSA provides clients full access to each application's parameters, allows administrators to specify named parameter preset combinations and execution limits for each application through simple configuration files. The JABAWS command-line client allows integration of JABAWS services into conventional scripts. JABAWS is made freely available under the Apache 2 license and can be obtained from: http://www.compbio.dundee.ac.uk/jabaws.

Resolving the double tension: Toward a new approach to measurement modeling in cross-national research

NASA Astrophysics Data System (ADS)

Medina, Tait Runnfeldt

The increasing global reach of survey research provides sociologists with new opportunities to pursue theory building and refinement through comparative analysis. However, comparison across a broad array of diverse contexts introduces methodological complexities related to the development of constructs (i.e., measurement modeling) that if not adequately recognized and properly addressed undermine the quality of research findings and cast doubt on the validity of substantive conclusions. The motivation for this dissertation arises from a concern that the availability of cross-national survey data has outpaced sociologists' ability to appropriately analyze and draw meaningful conclusions from such data. I examine the implicit assumptions and detail the limitations of three commonly used measurement models in cross-national analysis---summative scale, pooled factor model, and multiple-group factor model with measurement invariance. Using the orienting lens of the double tension I argue that a new approach to measurement modeling that incorporates important cross-national differences into the measurement process is needed. Two such measurement models---multiple-group factor model with partial measurement invariance (Byrne, Shavelson and Muthen 1989) and the alignment method (Asparouhov and Muthen 2014; Muthen and Asparouhov 2014)---are discussed in detail and illustrated using a sociologically relevant substantive example. I demonstrate that the former approach is vulnerable to an identification problem that arbitrarily impacts substantive conclusions. I conclude that the alignment method is built on model assumptions that are consistent with theoretical understandings of cross-national comparability and provides an approach to measurement modeling and construct development that is uniquely suited for cross-national research. The dissertation makes three major contributions: First, it provides theoretical justification for a new cross-national measurement model and explicates a link between theoretical conceptions of cross-national comparability and a statistical method. Second, it provides a clear and detailed discussion of model identification in multiple-group confirmatory factor analysis that is missing from the literature. This discussion sets the stage for the introduction of the identification problem within multiple-group confirmatory factor analysis with partial measurement invariance and the alternative approach to model identification employed by the alignment method. Third, it offers the first pedagogical presentation of the alignment method using a sociologically relevant example.

BiPACE 2D--graph-based multiple alignment for comprehensive 2D gas chromatography-mass spectrometry.

PubMed

Hoffmann, Nils; Wilhelm, Mathias; Doebbe, Anja; Niehaus, Karsten; Stoye, Jens

2014-04-01

Comprehensive 2D gas chromatography-mass spectrometry is an established method for the analysis of complex mixtures in analytical chemistry and metabolomics. It produces large amounts of data that require semiautomatic, but preferably automatic handling. This involves the location of significant signals (peaks) and their matching and alignment across different measurements. To date, there exist only a few openly available algorithms for the retention time alignment of peaks originating from such experiments that scale well with increasing sample and peak numbers, while providing reliable alignment results. We describe BiPACE 2D, an automated algorithm for retention time alignment of peaks from 2D gas chromatography-mass spectrometry experiments and evaluate it on three previously published datasets against the mSPA, SWPA and Guineu algorithms. We also provide a fourth dataset from an experiment studying the H2 production of two different strains of Chlamydomonas reinhardtii that is available from the MetaboLights database together with the experimental protocol, peak-detection results and manually curated multiple peak alignment for future comparability with newly developed algorithms. BiPACE 2D is contained in the freely available Maltcms framework, version 1.3, hosted at http://maltcms.sf.net, under the terms of the L-GPL v3 or Eclipse Open Source licenses. The software used for the evaluation along with the underlying datasets is available at the same location. The C.reinhardtii dataset is freely available at http://www.ebi.ac.uk/metabolights/MTBLS37.

A greedy, graph-based algorithm for the alignment of multiple homologous gene lists.

PubMed

Fostier, Jan; Proost, Sebastian; Dhoedt, Bart; Saeys, Yvan; Demeester, Piet; Van de Peer, Yves; Vandepoele, Klaas

2011-03-15

Many comparative genomics studies rely on the correct identification of homologous genomic regions using accurate alignment tools. In such case, the alphabet of the input sequences consists of complete genes, rather than nucleotides or amino acids. As optimal multiple sequence alignment is computationally impractical, a progressive alignment strategy is often employed. However, such an approach is susceptible to the propagation of alignment errors in early pairwise alignment steps, especially when dealing with strongly diverged genomic regions. In this article, we present a novel accurate and efficient greedy, graph-based algorithm for the alignment of multiple homologous genomic segments, represented as ordered gene lists. Based on provable properties of the graph structure, several heuristics are developed to resolve local alignment conflicts that occur due to gene duplication and/or rearrangement events on the different genomic segments. The performance of the algorithm is assessed by comparing the alignment results of homologous genomic segments in Arabidopsis thaliana to those obtained by using both a progressive alignment method and an earlier graph-based implementation. Especially for datasets that contain strongly diverged segments, the proposed method achieves a substantially higher alignment accuracy, and proves to be sufficiently fast for large datasets including a few dozens of eukaryotic genomes. http://bioinformatics.psb.ugent.be/software. The algorithm is implemented as a part of the i-ADHoRe 3.0 package.

CombAlign: a code for generating a one-to-many sequence alignment from a set of pairwise structure-based sequence alignments.

PubMed

Zhou, Carol L Ecale

2015-01-01

In order to better define regions of similarity among related protein structures, it is useful to identify the residue-residue correspondences among proteins. Few codes exist for constructing a one-to-many multiple sequence alignment derived from a set of structure or sequence alignments, and a need was evident for creating such a tool for combining pairwise structure alignments that would allow for insertion of gaps in the reference structure. This report describes a new Python code, CombAlign, which takes as input a set of pairwise sequence alignments (which may be structure based) and generates a one-to-many, gapped, multiple structure- or sequence-based sequence alignment (MSSA). The use and utility of CombAlign was demonstrated by generating gapped MSSAs using sets of pairwise structure-based sequence alignments between structure models of the matrix protein (VP40) and pre-small/secreted glycoprotein (sGP) of Reston Ebolavirus and the corresponding proteins of several other filoviruses. The gapped MSSAs revealed structure-based residue-residue correspondences, which enabled identification of structurally similar versus differing regions in the Reston proteins compared to each of the other corresponding proteins. CombAlign is a new Python code that generates a one-to-many, gapped, multiple structure- or sequence-based sequence alignment (MSSA) given a set of pairwise sequence alignments (which may be structure based). CombAlign has utility in assisting the user in distinguishing structurally conserved versus divergent regions on a reference protein structure relative to other closely related proteins. CombAlign was developed in Python 2.6, and the source code is available for download from the GitHub code repository.

COACH: profile-profile alignment of protein families using hidden Markov models.

PubMed

Edgar, Robert C; Sjölander, Kimmen

2004-05-22

Alignments of two multiple-sequence alignments, or statistical models of such alignments (profiles), have important applications in computational biology. The increased amount of information in a profile versus a single sequence can lead to more accurate alignments and more sensitive homolog detection in database searches. Several profile-profile alignment methods have been proposed and have been shown to improve sensitivity and alignment quality compared with sequence-sequence methods (such as BLAST) and profile-sequence methods (e.g. PSI-BLAST). Here we present a new approach to profile-profile alignment we call Comparison of Alignments by Constructing Hidden Markov Models (HMMs) (COACH). COACH aligns two multiple sequence alignments by constructing a profile HMM from one alignment and aligning the other to that HMM. We compare the alignment accuracy of COACH with two recently published methods: Yona and Levitt's prof_sim and Sadreyev and Grishin's COMPASS. On two sets of reference alignments selected from the FSSP database, we find that COACH is able, on average, to produce alignments giving the best coverage or the fewest errors, depending on the chosen parameter settings. COACH is freely available from www.drive5.com/lobster

High-speed multiple sequence alignment on a reconfigurable platform.

PubMed

Oliver, Tim; Schmidt, Bertil; Maskell, Douglas; Nathan, Darran; Clemens, Ralf

2006-01-01

Progressive alignment is a widely used approach to compute multiple sequence alignments (MSAs). However, aligning several hundred sequences by popular progressive alignment tools requires hours on sequential computers. Due to the rapid growth of sequence databases biologists have to compute MSAs in a far shorter time. In this paper we present a new approach to MSA on reconfigurable hardware platforms to gain high performance at low cost. We have constructed a linear systolic array to perform pairwise sequence distance computations using dynamic programming. This results in an implementation with significant runtime savings on a standard FPGA.

PASTA: Ultra-Large Multiple Sequence Alignment for Nucleotide and Amino-Acid Sequences

PubMed Central

Mirarab, Siavash; Nguyen, Nam; Guo, Sheng; Wang, Li-San; Kim, Junhyong

2015-01-01

Abstract We introduce PASTA, a new multiple sequence alignment algorithm. PASTA uses a new technique to produce an alignment given a guide tree that enables it to be both highly scalable and very accurate. We present a study on biological and simulated data with up to 200,000 sequences, showing that PASTA produces highly accurate alignments, improving on the accuracy and scalability of the leading alignment methods (including SATé). We also show that trees estimated on PASTA alignments are highly accurate—slightly better than SATé trees, but with substantial improvements relative to other methods. Finally, PASTA is faster than SATé, highly parallelizable, and requires relatively little memory. PMID:25549288

Aligning the unalignable: bacteriophage whole genome alignments.

PubMed

Bérard, Sèverine; Chateau, Annie; Pompidor, Nicolas; Guertin, Paul; Bergeron, Anne; Swenson, Krister M

2016-01-13

In recent years, many studies focused on the description and comparison of large sets of related bacteriophage genomes. Due to the peculiar mosaic structure of these genomes, few informative approaches for comparing whole genomes exist: dot plots diagrams give a mostly qualitative assessment of the similarity/dissimilarity between two or more genomes, and clustering techniques are used to classify genomes. Multiple alignments are conspicuously absent from this scene. Indeed, whole genome aligners interpret lack of similarity between sequences as an indication of rearrangements, insertions, or losses. This behavior makes them ill-prepared to align bacteriophage genomes, where even closely related strains can accomplish the same biological function with highly dissimilar sequences. In this paper, we propose a multiple alignment strategy that exploits functional collinearity shared by related strains of bacteriophages, and uses partial orders to capture mosaicism of sets of genomes. As classical alignments do, the computed alignments can be used to predict that genes have the same biological function, even in the absence of detectable similarity. The Alpha aligner implements these ideas in visual interactive displays, and is used to compute several examples of alignments of Staphylococcus aureus and Mycobacterium bacteriophages, involving up to 29 genomes. Using these datasets, we prove that Alpha alignments are at least as good as those computed by standard aligners. Comparison with the progressive Mauve aligner - which implements a partial order strategy, but whose alignments are linearized - shows a greatly improved interactive graphic display, while avoiding misalignments. Multiple alignments of whole bacteriophage genomes work, and will become an important conceptual and visual tool in comparative genomics of sets of related strains. A python implementation of Alpha, along with installation instructions for Ubuntu and OSX, is available on bitbucket (https://bitbucket.org/thekswenson/alpha).

Evolutionary profiles from the QR factorization of multiple sequence alignments

PubMed Central

Sethi, Anurag; O'Donoghue, Patrick; Luthey-Schulten, Zaida

2005-01-01

We present an algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of the homologous group. The method, based on the multidimensional QR factorization of numerically encoded multiple sequence alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. We observe a general trend that these smaller, more evolutionarily balanced profiles have comparable and, in many cases, better performance in database searches than conventional profiles containing hundreds of sequences, constructed in an iterative and computationally intensive procedure. For more diverse families or superfamilies, with sequence identity <30%, structural alignments, based purely on the geometry of the protein structures, provide better alignments than pure sequence-based methods. Merging the structure and sequence information allows the construction of accurate profiles for distantly related groups. These structure-based profiles outperformed other sequence-based methods for finding distant homologs and were used to identify a putative class II cysteinyl-tRNA synthetase (CysRS) in several archaea that eluded previous annotation studies. Phylogenetic analysis showed the putative class II CysRSs to be a monophyletic group and homology modeling revealed a constellation of active site residues similar to that in the known class I CysRS. PMID:15741270

SATCHMO-JS: a webserver for simultaneous protein multiple sequence alignment and phylogenetic tree construction.

PubMed

Hagopian, Raffi; Davidson, John R; Datta, Ruchira S; Samad, Bushra; Jarvis, Glen R; Sjölander, Kimmen

2010-07-01

We present the jump-start simultaneous alignment and tree construction using hidden Markov models (SATCHMO-JS) web server for simultaneous estimation of protein multiple sequence alignments (MSAs) and phylogenetic trees. The server takes as input a set of sequences in FASTA format, and outputs a phylogenetic tree and MSA; these can be viewed online or downloaded from the website. SATCHMO-JS is an extension of the SATCHMO algorithm, and employs a divide-and-conquer strategy to jump-start SATCHMO at a higher point in the phylogenetic tree, reducing the computational complexity of the progressive all-versus-all HMM-HMM scoring and alignment. Results on a benchmark dataset of 983 structurally aligned pairs from the PREFAB benchmark dataset show that SATCHMO-JS provides a statistically significant improvement in alignment accuracy over MUSCLE, Multiple Alignment using Fast Fourier Transform (MAFFT), ClustalW and the original SATCHMO algorithm. The SATCHMO-JS webserver is available at http://phylogenomics.berkeley.edu/satchmo-js. The datasets used in these experiments are available for download at http://phylogenomics.berkeley.edu/satchmo-js/supplementary/.

Hartman Testing of X-Ray Telescopes

NASA Technical Reports Server (NTRS)

Saha, Timo T.; Biskasch, Michael; Zhang, William W.

2013-01-01

Hartmann testing of x-ray telescopes is a simple test method to retrieve and analyze alignment errors and low-order circumferential errors of x-ray telescopes and their components. A narrow slit is scanned along the circumference of the telescope in front of the mirror and the centroids of the images are calculated. From the centroid data, alignment errors, radius variation errors, and cone-angle variation errors can be calculated. Mean cone angle, mean radial height (average radius), and the focal length of the telescope can also be estimated if the centroid data is measured at multiple focal plane locations. In this paper we present the basic equations that are used in the analysis process. These equations can be applied to full circumference or segmented x-ray telescopes. We use the Optical Surface Analysis Code (OSAC) to model a segmented x-ray telescope and show that the derived equations and accompanying analysis retrieves the alignment errors and low order circumferential errors accurately.

PVT: an efficient computational procedure to speed up next-generation sequence analysis.

PubMed

Maji, Ranjan Kumar; Sarkar, Arijita; Khatua, Sunirmal; Dasgupta, Subhasis; Ghosh, Zhumur

2014-06-04

High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat's serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during 'spliced alignment' and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system.

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments.

PubMed

Robinson, Mark D; De Souza, David P; Keen, Woon Wai; Saunders, Eleanor C; McConville, Malcolm J; Speed, Terence P; Likić, Vladimir A

2007-10-29

Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies. A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites. We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.

Mechanical design of multiple zone plates precision alignment apparatus for hard X-ray focusing in twenty-nanometer scale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shu, Deming; Liu, Jie; Gleber, Sophie C.

An enhanced mechanical design of multiple zone plates precision alignment apparatus for hard x-ray focusing in a twenty-nanometer scale is provided. The precision alignment apparatus includes a zone plate alignment base frame; a plurality of zone plates; and a plurality of zone plate holders, each said zone plate holder for mounting and aligning a respective zone plate for hard x-ray focusing. At least one respective positioning stage drives and positions each respective zone plate holder. Each respective positioning stage is mounted on the zone plate alignment base frame. A respective linkage component connects each respective positioning stage and the respectivemore » zone plate holder. The zone plate alignment base frame, each zone plate holder and each linkage component is formed of a selected material for providing thermal expansion stability and positioning stability for the precision alignment apparatus.« less

Plastid: nucleotide-resolution analysis of next-generation sequencing and genomics data.

PubMed

Dunn, Joshua G; Weissman, Jonathan S

2016-11-22

Next-generation sequencing (NGS) informs many biological questions with unprecedented depth and nucleotide resolution. These assays have created a need for analytical tools that enable users to manipulate data nucleotide-by-nucleotide robustly and easily. Furthermore, because many NGS assays encode information jointly within multiple properties of read alignments - for example, in ribosome profiling, the locations of ribosomes are jointly encoded in alignment coordinates and length - analytical tools are often required to extract the biological meaning from the alignments before analysis. Many assay-specific pipelines exist for this purpose, but there remains a need for user-friendly, generalized, nucleotide-resolution tools that are not limited to specific experimental regimes or analytical workflows. Plastid is a Python library designed specifically for nucleotide-resolution analysis of genomics and NGS data. As such, Plastid is designed to extract assay-specific information from read alignments while retaining generality and extensibility to novel NGS assays. Plastid represents NGS and other biological data as arrays of values associated with genomic or transcriptomic positions, and contains configurable tools to convert data from a variety of sources to such arrays. Plastid also includes numerous tools to manipulate even discontinuous genomic features, such as spliced transcripts, with nucleotide precision. Plastid automatically handles conversion between genomic and feature-centric coordinates, accounting for splicing and strand, freeing users of burdensome accounting. Finally, Plastid's data models use consistent and familiar biological idioms, enabling even beginners to develop sophisticated analytical workflows with minimal effort. Plastid is a versatile toolkit that has been used to analyze data from multiple NGS assays, including RNA-seq, ribosome profiling, and DMS-seq. It forms the genomic engine of our ORF annotation tool, ORF-RATER, and is readily adapted to novel NGS assays. Examples, tutorials, and extensive documentation can be found at https://plastid.readthedocs.io .

MultiSETTER: web server for multiple RNA structure comparison.

PubMed

Čech, Petr; Hoksza, David; Svozil, Daniel

2015-08-12

Understanding the architecture and function of RNA molecules requires methods for comparing and analyzing their tertiary and quaternary structures. While structural superposition of short RNAs is achievable in a reasonable time, large structures represent much bigger challenge. Therefore, we have developed a fast and accurate algorithm for RNA pairwise structure superposition called SETTER and implemented it in the SETTER web server. However, though biological relationships can be inferred by a pairwise structure alignment, key features preserved by evolution can be identified only from a multiple structure alignment. Thus, we extended the SETTER algorithm to the alignment of multiple RNA structures and developed the MultiSETTER algorithm. In this paper, we present the updated version of the SETTER web server that implements a user friendly interface to the MultiSETTER algorithm. The server accepts RNA structures either as the list of PDB IDs or as user-defined PDB files. After the superposition is computed, structures are visualized in 3D and several reports and statistics are generated. To the best of our knowledge, the MultiSETTER web server is the first publicly available tool for a multiple RNA structure alignment. The MultiSETTER server offers the visual inspection of an alignment in 3D space which may reveal structural and functional relationships not captured by other multiple alignment methods based either on a sequence or on secondary structure motifs.

Evolutionary profiles derived from the QR factorization of multiple structural alignments gives an economy of information.

PubMed

O'Donoghue, Patrick; Luthey-Schulten, Zaida

2005-02-25

We present a new algorithm, based on the multidimensional QR factorization, to remove redundancy from a multiple structural alignment by choosing representative protein structures that best preserve the phylogenetic tree topology of the homologous group. The classical QR factorization with pivoting, developed as a fast numerical solution to eigenvalue and linear least-squares problems of the form Ax=b, was designed to re-order the columns of A by increasing linear dependence. Removing the most linear dependent columns from A leads to the formation of a minimal basis set which well spans the phase space of the problem at hand. By recasting the problem of redundancy in multiple structural alignments into this framework, in which the matrix A now describes the multiple alignment, we adapted the QR factorization to produce a minimal basis set of protein structures which best spans the evolutionary (phase) space. The non-redundant and representative profiles obtained from this procedure, termed evolutionary profiles, are shown in initial results to outperform well-tested profiles in homology detection searches over a large sequence database. A measure of structural similarity between homologous proteins, Q(H), is presented. By properly accounting for the effect and presence of gaps, a phylogenetic tree computed using this metric is shown to be congruent with the maximum-likelihood sequence-based phylogeny. The results indicate that evolutionary information is indeed recoverable from the comparative analysis of protein structure alone. Applications of the QR ordering and this structural similarity metric to analyze the evolution of structure among key, universally distributed proteins involved in translation, and to the selection of representatives from an ensemble of NMR structures are also discussed.

Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis

PubMed Central

Iijima, Hirotaka; Fukutani, Naoto; Fukumoto, Takahiko; Uritani, Daisuke; Kaneda, Eishi; Ota, Kazuo; Kuroki, Hiroshi; Matsuda, Shuichi

2015-01-01

Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. PMID:26017348

Hydra multiple head star sensor and its in-flight self-calibration of optical heads alignment

NASA Astrophysics Data System (ADS)

Majewski, L.; Blarre, L.; Perrimon, N.; Kocher, Y.; Martinez, P. E.; Dussy, S.

2017-11-01

HYDRA is EADS SODERN new product line of APS-based autonomous star trackers. The baseline is a multiple head sensor made of three separated optical heads and one electronic unit. Actually the concept which was chosen offers more than three single-head star trackers working independently. Since HYDRA merges all fields of view the result is a more accurate, more robust and completely autonomous multiple-head sensor, releasing the AOCS from the need to manage the outputs of independent single-head star trackers. Specific to the multiple head architecture and the underlying data fusion, is the calibration of the relative alignments between the sensor optical heads. The performance of the sensor is related to its estimation of such alignments. HYDRA design is first reminded in this paper along with simplification it can bring at system level (AOCS). Then self-calibration of optical heads alignment is highlighted through descriptions and simulation results, thus demonstrating the performances of a key part of HYDRA multiple-head concept.

Dynamics and allostery of the ionotropic glutamate receptors and the ligand binding domain.

PubMed

Tobi, Dror

2016-02-01

The dynamics of the ligand-binding domain (LBD) and the intact ionotropic glutamate receptor (iGluR) were studied using Gaussian Network Model (GNM) analysis. The dynamics of LBDs with various allosteric modulators is compared using a novel method of multiple alignment of GNM modes of motion. The analysis reveals that allosteric effectors change the dynamics of amino acids at the upper lobe interface of the LBD dimer as well as at the hinge region between the upper- and lower- lobes. For the intact glutamate receptor the analysis show that the clamshell-like movement of the LBD upper and lower lobes is coupled to the bending of the trans-membrane domain (TMD) helices which may open the channel pore. The results offer a new insight on the mechanism of action of allosteric modulators on the iGluR and support the notion of TMD helices bending as a possible mechanism for channel opening. In addition, the study validates the methodology of multiple GNM modes alignment as a useful tool to study allosteric effect and its relation to proteins dynamics. © 2015 Wiley Periodicals, Inc.

gmos: Rapid Detection of Genome Mosaicism over Short Evolutionary Distances.

PubMed

Domazet-Lošo, Mirjana; Domazet-Lošo, Tomislav

2016-01-01

Prokaryotic and viral genomes are often altered by recombination and horizontal gene transfer. The existing methods for detecting recombination are primarily aimed at viral genomes or sets of loci, since the expensive computation of underlying statistical models often hinders the comparison of complete prokaryotic genomes. As an alternative, alignment-free solutions are more efficient, but cannot map (align) a query to subject genomes. To address this problem, we have developed gmos (Genome MOsaic Structure), a new program that determines the mosaic structure of query genomes when compared to a set of closely related subject genomes. The program first computes local alignments between query and subject genomes and then reconstructs the query mosaic structure by choosing the best local alignment for each query region. To accomplish the analysis quickly, the program mostly relies on pairwise alignments and constructs multiple sequence alignments over short overlapping subject regions only when necessary. This fine-tuned implementation achieves an efficiency comparable to an alignment-free tool. The program performs well for simulated and real data sets of closely related genomes and can be used for fast recombination detection; for instance, when a new prokaryotic pathogen is discovered. As an example, gmos was used to detect genome mosaicism in a pathogenic Enterococcus faecium strain compared to seven closely related genomes. The analysis took less than two minutes on a single 2.1 GHz processor. The output is available in fasta format and can be visualized using an accessory program, gmosDraw (freely available with gmos).

gmos: Rapid Detection of Genome Mosaicism over Short Evolutionary Distances

PubMed Central

Domazet-Lošo, Mirjana; Domazet-Lošo, Tomislav

2016-01-01

Prokaryotic and viral genomes are often altered by recombination and horizontal gene transfer. The existing methods for detecting recombination are primarily aimed at viral genomes or sets of loci, since the expensive computation of underlying statistical models often hinders the comparison of complete prokaryotic genomes. As an alternative, alignment-free solutions are more efficient, but cannot map (align) a query to subject genomes. To address this problem, we have developed gmos (Genome MOsaic Structure), a new program that determines the mosaic structure of query genomes when compared to a set of closely related subject genomes. The program first computes local alignments between query and subject genomes and then reconstructs the query mosaic structure by choosing the best local alignment for each query region. To accomplish the analysis quickly, the program mostly relies on pairwise alignments and constructs multiple sequence alignments over short overlapping subject regions only when necessary. This fine-tuned implementation achieves an efficiency comparable to an alignment-free tool. The program performs well for simulated and real data sets of closely related genomes and can be used for fast recombination detection; for instance, when a new prokaryotic pathogen is discovered. As an example, gmos was used to detect genome mosaicism in a pathogenic Enterococcus faecium strain compared to seven closely related genomes. The analysis took less than two minutes on a single 2.1 GHz processor. The output is available in fasta format and can be visualized using an accessory program, gmosDraw (freely available with gmos). PMID:27846272

Evaluation of sequence alignments and oligonucleotide probes with respect to three-dimensional structure of ribosomal RNA using ARB software package

PubMed Central

Kumar, Yadhu; Westram, Ralf; Kipfer, Peter; Meier, Harald; Ludwig, Wolfgang

2006-01-01

Background Availability of high-resolution RNA crystal structures for the 30S and 50S ribosomal subunits and the subsequent validation of comparative secondary structure models have prompted the biologists to use three-dimensional structure of ribosomal RNA (rRNA) for evaluating sequence alignments of rRNA genes. Furthermore, the secondary and tertiary structural features of rRNA are highly useful and successfully employed in designing rRNA targeted oligonucleotide probes intended for in situ hybridization experiments. RNA3D, a program to combine sequence alignment information with three-dimensional structure of rRNA was developed. Integration into ARB software package, which is used extensively by the scientific community for phylogenetic analysis and molecular probe designing, has substantially extended the functionality of ARB software suite with 3D environment. Results Three-dimensional structure of rRNA is visualized in OpenGL 3D environment with the abilities to change the display and overlay information onto the molecule, dynamically. Phylogenetic information derived from the multiple sequence alignments can be overlaid onto the molecule structure in a real time. Superimposition of both statistical and non-statistical sequence associated information onto the rRNA 3D structure can be done using customizable color scheme, which is also applied to a textual sequence alignment for reference. Oligonucleotide probes designed by ARB probe design tools can be mapped onto the 3D structure along with the probe accessibility models for evaluation with respect to secondary and tertiary structural conformations of rRNA. Conclusion Visualization of three-dimensional structure of rRNA in an intuitive display provides the biologists with the greater possibilities to carry out structure based phylogenetic analysis. Coupled with secondary structure models of rRNA, RNA3D program aids in validating the sequence alignments of rRNA genes and evaluating probe target sites. Superimposition of the information derived from the multiple sequence alignment onto the molecule dynamically allows the researchers to observe any sequence inherited characteristics (phylogenetic information) in real-time environment. The extended ARB software package is made freely available for the scientific community via . PMID:16672074

Global Alignment of Pairwise Protein Interaction Networks for Maximal Common Conserved Patterns

DOE PAGES

Tian, Wenhong; Samatova, Nagiza F.

2013-01-01

A number of tools for the alignment of protein-protein interaction (PPI) networks have laid the foundation for PPI network analysis. Most of alignment tools focus on finding conserved interaction regions across the PPI networks through either local or global mapping of similar sequences. Researchers are still trying to improve the speed, scalability, and accuracy of network alignment. In view of this, we introduce a connected-components based fast algorithm, HopeMap, for network alignment. Observing that the size of true orthologs across species is small comparing to the total number of proteins in all species, we take a different approach based onmore » a precompiled list of homologs identified by KO terms. Applying this approach to S. cerevisiae (yeast) and D. melanogaster (fly), E. coli K12 and S. typhimurium , E. coli K12 and C. crescenttus , we analyze all clusters identified in the alignment. The results are evaluated through up-to-date known gene annotations, gene ontology (GO), and KEGG ortholog groups (KO). Comparing to existing tools, our approach is fast with linear computational cost, highly accurate in terms of KO and GO terms specificity and sensitivity, and can be extended to multiple alignments easily.« less

Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue.

PubMed

Kowalski, William J; Yuan, Fangping; Nakane, Takeichiro; Masumoto, Hidetoshi; Dwenger, Marc; Ye, Fei; Tinney, Joseph P; Keller, Bradley B

2017-08-01

Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter, κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

What to do When Scalar Invariance Fails: The Extended Alignment Method for Multi-Group Factor Analysis Comparison of Latent Means Across Many Groups.

PubMed

Marsh, Herbert W; Guo, Jiesi; Parker, Philip D; Nagengast, Benjamin; Asparouhov, Tihomir; Muthén, Bengt; Dicke, Theresa

2017-01-12

Scalar invariance is an unachievable ideal that in practice can only be approximated; often using potentially questionable approaches such as partial invariance based on a stepwise selection of parameter estimates with large modification indices. Study 1 demonstrates an extension of the power and flexibility of the alignment approach for comparing latent factor means in large-scale studies (30 OECD countries, 8 factors, 44 items, N = 249,840), for which scalar invariance is typically not supported in the traditional confirmatory factor analysis approach to measurement invariance (CFA-MI). Importantly, we introduce an alignment-within-CFA (AwC) approach, transforming alignment from a largely exploratory tool into a confirmatory tool, and enabling analyses that previously have not been possible with alignment (testing the invariance of uniquenesses and factor variances/covariances; multiple-group MIMIC models; contrasts on latent means) and structural equation models more generally. Specifically, it also allowed a comparison of gender differences in a 30-country MIMIC AwC (i.e., a SEM with gender as a covariate) and a 60-group AwC CFA (i.e., 30 countries × 2 genders) analysis. Study 2, a simulation study following up issues raised in Study 1, showed that latent means were more accurately estimated with alignment than with the scalar CFA-MI, and particularly with partial invariance scalar models based on the heavily criticized stepwise selection strategy. In summary, alignment augmented by AwC provides applied researchers from diverse disciplines considerable flexibility to address substantively important issues when the traditional CFA-MI scalar model does not fit the data. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fitting in and feeling good: the relationships among peer alignment, instructor connectedness, and self-efficacy in undergraduate satisfaction with engineering

NASA Astrophysics Data System (ADS)

Micari, Marina; Pazos, Pilar

2016-07-01

This study examined the relationships among peer alignment (the feeling that one is similar in important ways to one's engineering peers), instructor connectedness (the sense that one knows and looks up to academic staff/faculty members in the department), self-efficacy for engineering class work (confidence in one's ability to successfully complete engineering class work), and engineering students' satisfaction with the major. A total of 135 sophomore (second-year university students) and junior (third-year students) engineering students were surveyed to measure these three variables. A multiple regression analysis showed that self-efficacy, peer alignment, and instructor connectedness predicted student satisfaction with the major, and that self-efficacy acted as a mediator between both peer alignment and instructor connectedness on the one hand, and satisfaction on the other. The authors offer suggestions for practice based on the results.

DNAAlignEditor: DNA alignment editor tool

PubMed Central

Sanchez-Villeda, Hector; Schroeder, Steven; Flint-Garcia, Sherry; Guill, Katherine E; Yamasaki, Masanori; McMullen, Michael D

2008-01-01

Background With advances in DNA re-sequencing methods and Next-Generation parallel sequencing approaches, there has been a large increase in genomic efforts to define and analyze the sequence variability present among individuals within a species. For very polymorphic species such as maize, this has lead to a need for intuitive, user-friendly software that aids the biologist, often with naïve programming capability, in tracking, editing, displaying, and exporting multiple individual sequence alignments. To fill this need we have developed a novel DNA alignment editor. Results We have generated a nucleotide sequence alignment editor (DNAAlignEditor) that provides an intuitive, user-friendly interface for manual editing of multiple sequence alignments with functions for input, editing, and output of sequence alignments. The color-coding of nucleotide identity and the display of associated quality score aids in the manual alignment editing process. DNAAlignEditor works as a client/server tool having two main components: a relational database that collects the processed alignments and a user interface connected to database through universal data access connectivity drivers. DNAAlignEditor can be used either as a stand-alone application or as a network application with multiple users concurrently connected. Conclusion We anticipate that this software will be of general interest to biologists and population genetics in editing DNA sequence alignments and analyzing natural sequence variation regardless of species, and will be particularly useful for manual alignment editing of sequences in species with high levels of polymorphism. PMID:18366684

Purification, developmental expression, and in silico characterization of α-amylase inhibitor from Echinochloa frumentacea.

PubMed

Panwar, Priyankar; Verma, A K; Dubey, Ashutosh

2018-05-01

Barnyard ( Echinochloa frumentacea ) and finger ( Eleusine coracana ) millet growing at northwestern Himalaya were explored for the α-amylase inhibitor (α-AI). The mature seeds of barnyard millet variety PRJ1 had maximum α-AI activity which increases in different developmental stage. α-AI was purified up to 22.25-fold from barnyard millet variety PRJ1. Semi-quantitative PCR of different developmental stages of barnyard millet seeds showed increased levels of the transcript from 7 to 28 days. Sequence analysis revealed that it contained 315 bp nucleotide which encodes 104 amino acid sequence with molecular weight 10.72 kDa. The predicted 3D structure of α-AI was 86.73% similar to a bifunctional inhibitor of ragi. In silico analysis of 71 α-AI protein sequences were carried out for biochemical features, homology search, multiple sequence alignment, phylogenetic tree construction, motif, and superfamily distribution of protein sequences. Analysis of multiple sequence alignment revealed the existence of conserved regions NPLP[S/G]CRWYVV[S/Q][Q/R]TCG[V/I] throughout sequences. Superfam analysis revealed that α-AI protein sequences were distributed among seven different superfamilies.

Accelerated probabilistic inference of RNA structure evolution

PubMed Central

Holmes, Ian

2005-01-01

Background Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered. Results We demonstrate how flexible classes of constraint can be imposed, greatly reducing the computational costs while maintaining a high quality of structural homology prediction. Any score-attributed context-free grammar (e.g. energy-based scoring schemes, or conditionally normalized Pair SCFGs) is amenable to this treatment. It is now possible to combine independent structural and alignment constraints of unprecedented general flexibility in Pair SCFG alignment algorithms. We outline several applications to the bioinformatics of RNA sequence and structure, including Waterman-Eggert N-best alignments and progressive multiple alignment. We evaluate the performance of the algorithm on test examples from the RFAM database. Conclusion A program, Stemloc, that implements these algorithms for efficient RNA sequence alignment and structure prediction is available under the GNU General Public License. PMID:15790387

Simple chained guide trees give high-quality protein multiple sequence alignments

PubMed Central

Boyce, Kieran; Sievers, Fabian; Higgins, Desmond G.

2014-01-01

Guide trees are used to decide the order of sequence alignment in the progressive multiple sequence alignment heuristic. These guide trees are often the limiting factor in making large alignments, and considerable effort has been expended over the years in making these quickly or accurately. In this article we show that, at least for protein families with large numbers of sequences that can be benchmarked with known structures, simple chained guide trees give the most accurate alignments. These also happen to be the fastest and simplest guide trees to construct, computationally. Such guide trees have a striking effect on the accuracy of alignments produced by some of the most widely used alignment packages. There is a marked increase in accuracy and a marked decrease in computational time, once the number of sequences goes much above a few hundred. This is true, even if the order of sequences in the guide tree is random. PMID:25002495

Parallel seed-based approach to multiple protein structure similarities detection

DOE PAGES

Chapuis, Guillaume; Le Boudic-Jamin, Mathilde; Andonov, Rumen; ...

2015-01-01

Finding similarities between protein structures is a crucial task in molecular biology. Most of the existing tools require proteins to be aligned in order-preserving way and only find single alignments even when multiple similar regions exist. We propose a new seed-based approach that discovers multiple pairs of similar regions. Its computational complexity is polynomial and it comes with a quality guarantee—the returned alignments have both root mean squared deviations (coordinate-based as well as internal-distances based) lower than a given threshold, if such exist. We do not require the alignments to be order preserving (i.e., we consider nonsequential alignments), which makesmore » our algorithm suitable for detecting similar domains when comparing multidomain proteins as well as to detect structural repetitions within a single protein. Because the search space for nonsequential alignments is much larger than for sequential ones, the computational burden is addressed by extensive use of parallel computing techniques: a coarse-grain level parallelism making use of available CPU cores for computation and a fine-grain level parallelism exploiting bit-level concurrency as well as vector instructions.« less

Iterative pass optimization of sequence data

NASA Technical Reports Server (NTRS)

Wheeler, Ward C.

2003-01-01

The problem of determining the minimum-cost hypothetical ancestral sequences for a given cladogram is known to be NP-complete. This "tree alignment" problem has motivated the considerable effort placed in multiple sequence alignment procedures. Wheeler in 1996 proposed a heuristic method, direct optimization, to calculate cladogram costs without the intervention of multiple sequence alignment. This method, though more efficient in time and more effective in cladogram length than many alignment-based procedures, greedily optimizes nodes based on descendent information only. In their proposal of an exact multiple alignment solution, Sankoff et al. in 1976 described a heuristic procedure--the iterative improvement method--to create alignments at internal nodes by solving a series of median problems. The combination of a three-sequence direct optimization with iterative improvement and a branch-length-based cladogram cost procedure, provides an algorithm that frequently results in superior (i.e., lower) cladogram costs. This iterative pass optimization is both computation and memory intensive, but economies can be made to reduce this burden. An example in arthropod systematics is discussed. c2003 The Willi Hennig Society. Published by Elsevier Science (USA). All rights reserved.

Analysis of multiple internal reflections in a parallel aligned liquid crystal on silicon SLM.

PubMed

Martínez, José Luis; Moreno, Ignacio; del Mar Sánchez-López, María; Vargas, Asticio; García-Martínez, Pascuala

2014-10-20

Multiple internal reflection effects on the optical modulation of a commercial reflective parallel-aligned liquid-crystal on silicon (PAL-LCoS) spatial light modulator (SLM) are analyzed. The display is illuminated with different wavelengths and different angles of incidence. Non-negligible Fabry-Perot (FP) effect is observed due to the sandwiched LC layer structure. A simplified physical model that quantitatively accounts for the observed phenomena is proposed. It is shown how the expected pure phase modulation response is substantially modified in the following aspects: 1) a coupled amplitude modulation, 2) a non-linear behavior of the phase modulation, 3) some amount of unmodulated light, and 4) a reduction of the effective phase modulation as the angle of incidence increases. Finally, it is shown that multiple reflections can be useful since the effect of a displayed diffraction grating is doubled on a beam that is reflected twice through the LC layer, thus rendering gratings with doubled phase modulation depth.

Base-By-Base: single nucleotide-level analysis of whole viral genome alignments.

PubMed

Brodie, Ryan; Smith, Alex J; Roper, Rachel L; Tcherepanov, Vasily; Upton, Chris

2004-07-14

With ever increasing numbers of closely related virus genomes being sequenced, it has become desirable to be able to compare two genomes at a level more detailed than gene content because two strains of an organism may share the same set of predicted genes but still differ in their pathogenicity profiles. For example, detailed comparison of multiple isolates of the smallpox virus genome (each approximately 200 kb, with 200 genes) is not feasible without new bioinformatics tools. A software package, Base-By-Base, has been developed that provides visualization tools to enable researchers to 1) rapidly identify and correct alignment errors in large, multiple genome alignments; and 2) generate tabular and graphical output of differences between the genomes at the nucleotide level. Base-By-Base uses detailed annotation information about the aligned genomes and can list each predicted gene with nucleotide differences, display whether variations occur within promoter regions or coding regions and whether these changes result in amino acid substitutions. Base-By-Base can connect to our mySQL database (Virus Orthologous Clusters; VOCs) to retrieve detailed annotation information about the aligned genomes or use information from text files. Base-By-Base enables users to quickly and easily compare large viral genomes; it highlights small differences that may be responsible for important phenotypic differences such as virulence. It is available via the Internet using Java Web Start and runs on Macintosh, PC and Linux operating systems with the Java 1.4 virtual machine.

Multiple network alignment via multiMAGNA+.

PubMed

Vijayan, Vipin; Milenkovic, Tijana

2017-08-21

Network alignment (NA) aims to find a node mapping that identifies topologically or functionally similar network regions between molecular networks of different species. Analogous to genomic sequence alignment, NA can be used to transfer biological knowledge from well- to poorly-studied species between aligned network regions. Pairwise NA (PNA) finds similar regions between two networks while multiple NA (MNA) can align more than two networks. We focus on MNA. Existing MNA methods aim to maximize total similarity over all aligned nodes (node conservation). Then, they evaluate alignment quality by measuring the amount of conserved edges, but only after the alignment is constructed. Directly optimizing edge conservation during alignment construction in addition to node conservation may result in superior alignments. Thus, we present a novel MNA method called multiMAGNA++ that can achieve this. Indeed, multiMAGNA++ outperforms or is on par with existing MNA methods, while often completing faster than existing methods. That is, multiMAGNA++ scales well to larger network data and can be parallelized effectively. During method evaluation, we also introduce new MNA quality measures to allow for more fair MNA method comparison compared to the existing alignment quality measures. MultiMAGNA++ code is available on the method's web page at http://nd.edu/~cone/multiMAGNA++/.

SubVis: an interactive R package for exploring the effects of multiple substitution matrices on pairwise sequence alignment

PubMed Central

Coan, Heather B.; Youker, Robert T.

2017-01-01

Understanding how proteins mutate is critical to solving a host of biological problems. Mutations occur when an amino acid is substituted for another in a protein sequence. The set of likelihoods for amino acid substitutions is stored in a matrix and input to alignment algorithms. The quality of the resulting alignment is used to assess the similarity of two or more sequences and can vary according to assumptions modeled by the substitution matrix. Substitution strategies with minor parameter variations are often grouped together in families. For example, the BLOSUM and PAM matrix families are commonly used because they provide a standard, predefined way of modeling substitutions. However, researchers often do not know if a given matrix family or any individual matrix within a family is the most suitable. Furthermore, predefined matrix families may inaccurately reflect a particular hypothesis that a researcher wishes to model or otherwise result in unsatisfactory alignments. In these cases, the ability to compare the effects of one or more custom matrices may be needed. This laborious process is often performed manually because the ability to simultaneously load multiple matrices and then compare their effects on alignments is not readily available in current software tools. This paper presents SubVis, an interactive R package for loading and applying multiple substitution matrices to pairwise alignments. Users can simultaneously explore alignments resulting from multiple predefined and custom substitution matrices. SubVis utilizes several of the alignment functions found in R, a common language among protein scientists. Functions are tied together with the Shiny platform which allows the modification of input parameters. Information regarding alignment quality and individual amino acid substitutions is displayed with the JavaScript language which provides interactive visualizations for revealing both high-level and low-level alignment information. PMID:28674656

Curation of microarray oligonucleotides and corresponding ESTs/cDNAs used for gene expression analysis in zebra finches.

PubMed

Lovell, Peter V; Huizinga, Nicole A; Getachew, Abel; Mees, Brianna; Friedrich, Samantha R; Wirthlin, Morgan; Mello, Claudio V

2018-05-18

Zebra finches are a major model organism for investigating mechanisms of vocal learning, a trait that enables spoken language in humans. The development of cDNA collections with expressed sequence tags (ESTs) and microarrays has allowed for extensive molecular characterizations of circuitry underlying vocal learning and production. However, poor database curation can lead to errors in transcriptome and bioinformatics analyses, limiting the impact of these resources. Here we used genomic alignments and synteny analysis for orthology verification to curate and reannotate ~ 35% of the oligonucleotides and corresponding ESTs/cDNAs that make-up Agilent microarrays for gene expression analysis in finches. We found that: (1) 5475 out of 43,084 oligos (a) failed to align to the zebra finch genome, (b) aligned to multiple loci, or (c) aligned to Chr_un only, and thus need to be flagged until a better genome assembly is available, or (d) reflect cloning artifacts; (2) Out of 9635 valid oligos examined further, 3120 were incorrectly named, including 1533 with no known orthologs; and (3) 2635 oligos required name update. The resulting curated dataset provides a reference for correcting gene identification errors in previous finch microarrays studies, and avoiding such errors in future studies.

Diffeomorphic functional brain surface alignment: Functional demons.

PubMed

Nenning, Karl-Heinz; Liu, Hesheng; Ghosh, Satrajit S; Sabuncu, Mert R; Schwartz, Ernst; Langs, Georg

2017-08-01

Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolutionary distances in the twilight zone--a rational kernel approach.

PubMed

Schwarz, Roland F; Fletcher, William; Förster, Frank; Merget, Benjamin; Wolf, Matthias; Schultz, Jörg; Markowetz, Florian

2010-12-31

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.

AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

PubMed

Di Pietro, C; Di Pietro, V; Emmanuele, G; Ferro, A; Maugeri, T; Modica, E; Pigola, G; Pulvirenti, A; Purrello, M; Ragusa, M; Scalia, M; Shasha, D; Travali, S; Zimmitti, V

2003-01-01

In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

Desorption Kinetics of Ar, Kr, Xe, N2, O2, CO, Methane, Ethane, and Propane from Graphene and Amorphous Solid Water Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, R. Scott; May, Robert A.; Kay, Bruce D.

2016-03-03

The desorption kinetics for Ar, Kr, Xe, N2, O2, CO, methane, ethane, and propane from grapheme covered Pt(111) and amorphous solid water (ASW) surfaces are investigated using temperature programmed desorption (TPD). The TPD spectra for all of the adsorbates from graphene have well-resolved first, second, third, and multi- layer desorption peaks. The alignment of the leading edges is consistent the zero-order desorption for all of the adsorbates. An Arrhenius analysis is used to obtain desorption energies and prefactors for desorption from graphene for all of the adsorbates. In contrast, the leading desorption edges for the adsorbates from ASW do notmore » align (for coverages < 2 ML). The non-alignment of TPD leading edges suggests that there are multiple desorption binding sites on the ASW surface. Inversion analysis is used to obtain the coverage dependent desorption energies and prefactors for desorption from ASW for all of the adsorbates.« less

Statistical discovery of site inter-dependencies in sub-molecular hierarchical protein structuring

PubMed Central

2012-01-01

Background Much progress has been made in understanding the 3D structure of proteins using methods such as NMR and X-ray crystallography. The resulting 3D structures are extremely informative, but do not always reveal which sites and residues within the structure are of special importance. Recently, there are indications that multiple-residue, sub-domain structural relationships within the larger 3D consensus structure of a protein can be inferred from the analysis of the multiple sequence alignment data of a protein family. These intra-dependent clusters of associated sites are used to indicate hierarchical inter-residue relationships within the 3D structure. To reveal the patterns of associations among individual amino acids or sub-domain components within the structure, we apply a k-modes attribute (aligned site) clustering algorithm to the ubiquitin and transthyretin families in order to discover associations among groups of sites within the multiple sequence alignment. We then observe what these associations imply within the 3D structure of these two protein families. Results The k-modes site clustering algorithm we developed maximizes the intra-group interdependencies based on a normalized mutual information measure. The clusters formed correspond to sub-structural components or binding and interface locations. Applying this data-directed method to the ubiquitin and transthyretin protein family multiple sequence alignments as a test bed, we located numerous interesting associations of interdependent sites. These clusters were then arranged into cluster tree diagrams which revealed four structural sub-domains within the single domain structure of ubiquitin and a single large sub-domain within transthyretin associated with the interface among transthyretin monomers. In addition, several clusters of mutually interdependent sites were discovered for each protein family, each of which appear to play an important role in the molecular structure and/or function. Conclusions Our results demonstrate that the method we present here using a k-modes site clustering algorithm based on interdependency evaluation among sites obtained from a sequence alignment of homologous proteins can provide significant insights into the complex, hierarchical inter-residue structural relationships within the 3D structure of a protein family. PMID:22793672

Statistical discovery of site inter-dependencies in sub-molecular hierarchical protein structuring.

PubMed

Durston, Kirk K; Chiu, David Ky; Wong, Andrew Kc; Li, Gary Cl

2012-07-13

Much progress has been made in understanding the 3D structure of proteins using methods such as NMR and X-ray crystallography. The resulting 3D structures are extremely informative, but do not always reveal which sites and residues within the structure are of special importance. Recently, there are indications that multiple-residue, sub-domain structural relationships within the larger 3D consensus structure of a protein can be inferred from the analysis of the multiple sequence alignment data of a protein family. These intra-dependent clusters of associated sites are used to indicate hierarchical inter-residue relationships within the 3D structure. To reveal the patterns of associations among individual amino acids or sub-domain components within the structure, we apply a k-modes attribute (aligned site) clustering algorithm to the ubiquitin and transthyretin families in order to discover associations among groups of sites within the multiple sequence alignment. We then observe what these associations imply within the 3D structure of these two protein families. The k-modes site clustering algorithm we developed maximizes the intra-group interdependencies based on a normalized mutual information measure. The clusters formed correspond to sub-structural components or binding and interface locations. Applying this data-directed method to the ubiquitin and transthyretin protein family multiple sequence alignments as a test bed, we located numerous interesting associations of interdependent sites. These clusters were then arranged into cluster tree diagrams which revealed four structural sub-domains within the single domain structure of ubiquitin and a single large sub-domain within transthyretin associated with the interface among transthyretin monomers. In addition, several clusters of mutually interdependent sites were discovered for each protein family, each of which appear to play an important role in the molecular structure and/or function. Our results demonstrate that the method we present here using a k-modes site clustering algorithm based on interdependency evaluation among sites obtained from a sequence alignment of homologous proteins can provide significant insights into the complex, hierarchical inter-residue structural relationships within the 3D structure of a protein family.

ExScalibur: A High-Performance Cloud-Enabled Suite for Whole Exome Germline and Somatic Mutation Identification.

PubMed

Bao, Riyue; Hernandez, Kyle; Huang, Lei; Kang, Wenjun; Bartom, Elizabeth; Onel, Kenan; Volchenboum, Samuel; Andrade, Jorge

2015-01-01

Whole exome sequencing has facilitated the discovery of causal genetic variants associated with human diseases at deep coverage and low cost. In particular, the detection of somatic mutations from tumor/normal pairs has provided insights into the cancer genome. Although there is an abundance of publicly-available software for the detection of germline and somatic variants, concordance is generally limited among variant callers and alignment algorithms. Successful integration of variants detected by multiple methods requires in-depth knowledge of the software, access to high-performance computing resources, and advanced programming techniques. We present ExScalibur, a set of fully automated, highly scalable and modulated pipelines for whole exome data analysis. The suite integrates multiple alignment and variant calling algorithms for the accurate detection of germline and somatic mutations with close to 99% sensitivity and specificity. ExScalibur implements streamlined execution of analytical modules, real-time monitoring of pipeline progress, robust handling of errors and intuitive documentation that allows for increased reproducibility and sharing of results and workflows. It runs on local computers, high-performance computing clusters and cloud environments. In addition, we provide a data analysis report utility to facilitate visualization of the results that offers interactive exploration of quality control files, read alignment and variant calls, assisting downstream customization of potential disease-causing mutations. ExScalibur is open-source and is also available as a public image on Amazon cloud.

New Challenges of the Computation of Multiple Sequence Alignments in the High-Throughput Era (2010 JGI/ANL HPC Workshop)

ScienceCinema

Notredame, Cedric

2018-05-02

Cedric Notredame from the Centre for Genomic Regulation gives a presentation on New Challenges of the Computation of Multiple Sequence Alignments in the High-Throughput Era at the JGI/Argonne HPC Workshop on January 26, 2010.

[Analyzing and tracking preoperative and intraoperative astigmatism].

PubMed

Perez, M

2012-03-01

Precise evaluation of preoperative astigmatism is the first step optimizing outcomes. This begins with office-based evaluation of astigmatism; corneal astigmatism is evaluated by keratometry, traditionally by Javal keratometry, but now including topography, whether Placido- or elevation-based, which allows for detailed analysis of even irregular astigmatism, including the corneal periphery, which is invaluable. Aberrometers, essentially "super-auto refractors", allow the incorporation of additional data into the qualitative analysis of astigmatism. The correlation between these multiple preoperative data helps to differentiate between corneal and total astigmatism, to infer the lenticular astigmatism, and to integrate all of these data into the clinical decision-making process. Immediately preoperatively, the 0 and 180° axes are marked; then, with the aid of a special marker, the axis of alignment for the toric IOL is also marked. Once the cataract is removed, the toric IOL is injected and pre-aligned; the viscoelastic is carefully removed, particularly from between the IOL and posterior capsule, with the toric IOL being definitively aligned at this point. These alignment techniques represent a major advance, soon to be indispensible for toric IOL surgery, which will certainly continue to grow in the future. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Two Simple and Efficient Algorithms to Compute the SP-Score Objective Function of a Multiple Sequence Alignment.

PubMed

Ranwez, Vincent

2016-01-01

Multiple sequence alignment (MSA) is a crucial step in many molecular analyses and many MSA tools have been developed. Most of them use a greedy approach to construct a first alignment that is then refined by optimizing the sum of pair score (SP-score). The SP-score estimation is thus a bottleneck for most MSA tools since it is repeatedly required and is time consuming. Given an alignment of n sequences and L sites, I introduce here optimized solutions reaching O(nL) time complexity for affine gap cost, instead of O(n2L), which are easy to implement.

Combining peak- and chromatogram-based retention time alignment algorithms for multiple chromatography-mass spectrometry datasets.

PubMed

Hoffmann, Nils; Keck, Matthias; Neuweger, Heiko; Wilhelm, Mathias; Högy, Petra; Niehaus, Karsten; Stoye, Jens

2012-08-27

Modern analytical methods in biology and chemistry use separation techniques coupled to sensitive detectors, such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These hyphenated methods provide high-dimensional data. Comparing such data manually to find corresponding signals is a laborious task, as each experiment usually consists of thousands of individual scans, each containing hundreds or even thousands of distinct signals. In order to allow for successful identification of metabolites or proteins within such data, especially in the context of metabolomics and proteomics, an accurate alignment and matching of corresponding features between two or more experiments is required. Such a matching algorithm should capture fluctuations in the chromatographic system which lead to non-linear distortions on the time axis, as well as systematic changes in recorded intensities. Many different algorithms for the retention time alignment of GC-MS and LC-MS data have been proposed and published, but all of them focus either on aligning previously extracted peak features or on aligning and comparing the complete raw data containing all available features. In this paper we introduce two algorithms for retention time alignment of multiple GC-MS datasets: multiple alignment by bidirectional best hits peak assignment and cluster extension (BIPACE) and center-star multiple alignment by pairwise partitioned dynamic time warping (CeMAPP-DTW). We show how the similarity-based peak group matching method BIPACE may be used for multiple alignment calculation individually and how it can be used as a preprocessing step for the pairwise alignments performed by CeMAPP-DTW. We evaluate the algorithms individually and in combination on a previously published small GC-MS dataset studying the Leishmania parasite and on a larger GC-MS dataset studying grains of wheat (Triticum aestivum). We have shown that BIPACE achieves very high precision and recall and a very low number of false positive peak assignments on both evaluation datasets. CeMAPP-DTW finds a high number of true positives when executed on its own, but achieves even better results when BIPACE is used to constrain its search space. The source code of both algorithms is included in the OpenSource software framework Maltcms, which is available from http://maltcms.sf.net. The evaluation scripts of the present study are available from the same source.

Combining peak- and chromatogram-based retention time alignment algorithms for multiple chromatography-mass spectrometry datasets

PubMed Central

2012-01-01

Background Modern analytical methods in biology and chemistry use separation techniques coupled to sensitive detectors, such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These hyphenated methods provide high-dimensional data. Comparing such data manually to find corresponding signals is a laborious task, as each experiment usually consists of thousands of individual scans, each containing hundreds or even thousands of distinct signals. In order to allow for successful identification of metabolites or proteins within such data, especially in the context of metabolomics and proteomics, an accurate alignment and matching of corresponding features between two or more experiments is required. Such a matching algorithm should capture fluctuations in the chromatographic system which lead to non-linear distortions on the time axis, as well as systematic changes in recorded intensities. Many different algorithms for the retention time alignment of GC-MS and LC-MS data have been proposed and published, but all of them focus either on aligning previously extracted peak features or on aligning and comparing the complete raw data containing all available features. Results In this paper we introduce two algorithms for retention time alignment of multiple GC-MS datasets: multiple alignment by bidirectional best hits peak assignment and cluster extension (BIPACE) and center-star multiple alignment by pairwise partitioned dynamic time warping (CeMAPP-DTW). We show how the similarity-based peak group matching method BIPACE may be used for multiple alignment calculation individually and how it can be used as a preprocessing step for the pairwise alignments performed by CeMAPP-DTW. We evaluate the algorithms individually and in combination on a previously published small GC-MS dataset studying the Leishmania parasite and on a larger GC-MS dataset studying grains of wheat (Triticum aestivum). Conclusions We have shown that BIPACE achieves very high precision and recall and a very low number of false positive peak assignments on both evaluation datasets. CeMAPP-DTW finds a high number of true positives when executed on its own, but achieves even better results when BIPACE is used to constrain its search space. The source code of both algorithms is included in the OpenSource software framework Maltcms, which is available from http://maltcms.sf.net. The evaluation scripts of the present study are available from the same source. PMID:22920415

PVT: An Efficient Computational Procedure to Speed up Next-generation Sequence Analysis

PubMed Central

2014-01-01

Background High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat’s serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. Results We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during ‘spliced alignment’ and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. Conclusions PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system. PMID:24894600

aLeaves facilitates on-demand exploration of metazoan gene family trees on MAFFT sequence alignment server with enhanced interactivity.

PubMed

Kuraku, Shigehiro; Zmasek, Christian M; Nishimura, Osamu; Katoh, Kazutaka

2013-07-01

We report a new web server, aLeaves (http://aleaves.cdb.riken.jp/), for homologue collection from diverse animal genomes. In molecular comparative studies involving multiple species, orthology identification is the basis on which most subsequent biological analyses rely. It can be achieved most accurately by explicit phylogenetic inference. More and more species are subjected to large-scale sequencing, but the resultant resources are scattered in independent project-based, and multi-species, but separate, web sites. This complicates data access and is becoming a serious barrier to the comprehensiveness of molecular phylogenetic analysis. aLeaves, launched to overcome this difficulty, collects sequences similar to an input query sequence from various data sources. The collected sequences can be passed on to the MAFFT sequence alignment server (http://mafft.cbrc.jp/alignment/server/), which has been significantly improved in interactivity. This update enables to switch between (i) sequence selection using the Archaeopteryx tree viewer, (ii) multiple sequence alignment and (iii) tree inference. This can be performed as a loop until one reaches a sensible data set, which minimizes redundancy for better visibility and handling in phylogenetic inference while covering relevant taxa. The work flow achieved by the seamless link between aLeaves and MAFFT provides a convenient online platform to address various questions in zoology and evolutionary biology.

Case-related factors affecting cutting errors of the proximal tibia in total knee arthroplasty assessed by computer navigation.

PubMed

Tsukeoka, Tadashi; Tsuneizumi, Yoshikazu; Yoshino, Kensuke; Suzuki, Mashiko

2018-05-01

The aim of this study was to determine factors that contribute to bone cutting errors of conventional instrumentation for tibial resection in total knee arthroplasty (TKA) as assessed by an image-free navigation system. The hypothesis is that preoperative varus alignment is a significant contributory factor to tibial bone cutting errors. This was a prospective study of a consecutive series of 72 TKAs. The amount of the tibial first-cut errors with reference to the planned cutting plane in both coronal and sagittal planes was measured by an image-free computer navigation system. Multiple regression models were developed with the amount of tibial cutting error in the coronal and sagittal planes as dependent variables and sex, age, disease, height, body mass index, preoperative alignment, patellar height (Insall-Salvati ratio) and preoperative flexion angle as independent variables. Multiple regression analysis showed that sex (male gender) (R = 0.25 p = 0.047) and preoperative varus alignment (R = 0.42, p = 0.001) were positively associated with varus tibial cutting errors in the coronal plane. In the sagittal plane, none of the independent variables was significant. When performing TKA in varus deformity, careful confirmation of the bone cutting surface should be performed to avoid varus alignment. The results of this study suggest technical considerations that can help a surgeon achieve more accurate component placement. IV.

aLeaves facilitates on-demand exploration of metazoan gene family trees on MAFFT sequence alignment server with enhanced interactivity

PubMed Central

Kuraku, Shigehiro; Zmasek, Christian M.; Nishimura, Osamu; Katoh, Kazutaka

2013-01-01

We report a new web server, aLeaves (http://aleaves.cdb.riken.jp/), for homologue collection from diverse animal genomes. In molecular comparative studies involving multiple species, orthology identification is the basis on which most subsequent biological analyses rely. It can be achieved most accurately by explicit phylogenetic inference. More and more species are subjected to large-scale sequencing, but the resultant resources are scattered in independent project-based, and multi-species, but separate, web sites. This complicates data access and is becoming a serious barrier to the comprehensiveness of molecular phylogenetic analysis. aLeaves, launched to overcome this difficulty, collects sequences similar to an input query sequence from various data sources. The collected sequences can be passed on to the MAFFT sequence alignment server (http://mafft.cbrc.jp/alignment/server/), which has been significantly improved in interactivity. This update enables to switch between (i) sequence selection using the Archaeopteryx tree viewer, (ii) multiple sequence alignment and (iii) tree inference. This can be performed as a loop until one reaches a sensible data set, which minimizes redundancy for better visibility and handling in phylogenetic inference while covering relevant taxa. The work flow achieved by the seamless link between aLeaves and MAFFT provides a convenient online platform to address various questions in zoology and evolutionary biology. PMID:23677614

Protein alignment algorithms with an efficient backtracking routine on multiple GPUs.

PubMed

Blazewicz, Jacek; Frohmberg, Wojciech; Kierzynka, Michal; Pesch, Erwin; Wojciechowski, Pawel

2011-05-20

Pairwise sequence alignment methods are widely used in biological research. The increasing number of sequences is perceived as one of the upcoming challenges for sequence alignment methods in the nearest future. To overcome this challenge several GPU (Graphics Processing Unit) computing approaches have been proposed lately. These solutions show a great potential of a GPU platform but in most cases address the problem of sequence database scanning and computing only the alignment score whereas the alignment itself is omitted. Thus, the need arose to implement the global and semiglobal Needleman-Wunsch, and Smith-Waterman algorithms with a backtracking procedure which is needed to construct the alignment. In this paper we present the solution that performs the alignment of every given sequence pair, which is a required step for progressive multiple sequence alignment methods, as well as for DNA recognition at the DNA assembly stage. Performed tests show that the implementation, with performance up to 6.3 GCUPS on a single GPU for affine gap penalties, is very efficient in comparison to other CPU and GPU-based solutions. Moreover, multiple GPUs support with load balancing makes the application very scalable. The article shows that the backtracking procedure of the sequence alignment algorithms may be designed to fit in with the GPU architecture. Therefore, our algorithm, apart from scores, is able to compute pairwise alignments. This opens a wide range of new possibilities, allowing other methods from the area of molecular biology to take advantage of the new computational architecture. Performed tests show that the efficiency of the implementation is excellent. Moreover, the speed of our GPU-based algorithms can be almost linearly increased when using more than one graphics card.

Optimizing multiple sequence alignments using a genetic algorithm based on three objectives: structural information, non-gaps percentage and totally conserved columns.

PubMed

Ortuño, Francisco M; Valenzuela, Olga; Rojas, Fernando; Pomares, Hector; Florido, Javier P; Urquiza, Jose M; Rojas, Ignacio

2013-09-01

Multiple sequence alignments (MSAs) are widely used approaches in bioinformatics to carry out other tasks such as structure predictions, biological function analyses or phylogenetic modeling. However, current tools usually provide partially optimal alignments, as each one is focused on specific biological features. Thus, the same set of sequences can produce different alignments, above all when sequences are less similar. Consequently, researchers and biologists do not agree about which is the most suitable way to evaluate MSAs. Recent evaluations tend to use more complex scores including further biological features. Among them, 3D structures are increasingly being used to evaluate alignments. Because structures are more conserved in proteins than sequences, scores with structural information are better suited to evaluate more distant relationships between sequences. The proposed multiobjective algorithm, based on the non-dominated sorting genetic algorithm, aims to jointly optimize three objectives: STRIKE score, non-gaps percentage and totally conserved columns. It was significantly assessed on the BAliBASE benchmark according to the Kruskal-Wallis test (P < 0.01). This algorithm also outperforms other aligners, such as ClustalW, Multiple Sequence Alignment Genetic Algorithm (MSA-GA), PRRP, DIALIGN, Hidden Markov Model Training (HMMT), Pattern-Induced Multi-sequence Alignment (PIMA), MULTIALIGN, Sequence Alignment Genetic Algorithm (SAGA), PILEUP, Rubber Band Technique Genetic Algorithm (RBT-GA) and Vertical Decomposition Genetic Algorithm (VDGA), according to the Wilcoxon signed-rank test (P < 0.05), whereas it shows results not significantly different to 3D-COFFEE (P > 0.05) with the advantage of being able to use less structures. Structural information is included within the objective function to evaluate more accurately the obtained alignments. The source code is available at http://www.ugr.es/~fortuno/MOSAStrE/MO-SAStrE.zip.

Sequence harmony: detecting functional specificity from alignments

PubMed Central

Feenstra, K. Anton; Pirovano, Walter; Krab, Klaas; Heringa, Jaap

2007-01-01

Multiple sequence alignments are often used for the identification of key specificity-determining residues within protein families. We present a web server implementation of the Sequence Harmony (SH) method previously introduced. SH accurately detects subfamily specific positions from a multiple alignment by scoring compositional differences between subfamilies, without imposing conservation. The SH web server allows a quick selection of subtype specific sites from a multiple alignment given a subfamily grouping. In addition, it allows the predicted sites to be directly mapped onto a protein structure and displayed. We demonstrate the use of the SH server using the family of plant mitochondrial alternative oxidases (AOX). In addition, we illustrate the usefulness of combining sequence and structural information by showing that the predicted sites are clustered into a few distinct regions in an AOX homology model. The SH web server can be accessed at www.ibi.vu.nl/programs/seqharmwww. PMID:17584793

Fourier transform power spectrum is a potential measure of tissue alignment in standard MRI: A multiple sclerosis study.

PubMed

Sharma, Shrushrita; Zhang, Yunyan

2017-01-01

Loss of tissue coherency in brain white matter is found in many neurological diseases such as multiple sclerosis (MS). While several approaches have been proposed to evaluate white matter coherency including fractional anisotropy and fiber tracking in diffusion-weighted imaging, few are available for standard magnetic resonance imaging (MRI). Here we present an image post-processing method for this purpose based on Fourier transform (FT) power spectrum. T2-weighted images were collected from 19 patients (10 relapsing-remitting and 9 secondary progressive MS) and 19 age- and gender-matched controls. Image processing steps included: computation, normalization, and thresholding of FT power spectrum; determination of tissue alignment profile and dominant alignment direction; and calculation of alignment complexity using a new measure named angular entropy. To test the validity of this method, we used a highly organized brain white matter structure, corpus callosum. Six regions of interest were examined from the left, central and right aspects of both genu and splenium. We found that the dominant orientation of each ROI derived from our method was significantly correlated with the predicted directions based on anatomy. There was greater angular entropy in patients than controls, and a trend to be greater in secondary progressive MS patients. These findings suggest that it is possible to detect tissue alignment and anisotropy using traditional MRI, which are routinely acquired in clinical practice. Analysis of FT power spectrum may become a new approach for advancing the evaluation and management of patients with MS and similar disorders. Further confirmation is warranted.

Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis.

PubMed

Aniba, Mohamed Radhouene; Siguenza, Sophie; Friedrich, Anne; Plewniak, Frédéric; Poch, Olivier; Marchler-Bauer, Aron; Thompson, Julie Dawn

2009-01-01

The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented.

Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis

PubMed Central

Aniba, Mohamed Radhouene; Siguenza, Sophie; Friedrich, Anne; Plewniak, Frédéric; Poch, Olivier; Marchler-Bauer, Aron

2009-01-01

The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented. PMID:18971242

YAHA: fast and flexible long-read alignment with optimal breakpoint detection.

PubMed

Faust, Gregory G; Hall, Ira M

2012-10-01

With improved short-read assembly algorithms and the recent development of long-read sequencers, split mapping will soon be the preferred method for structural variant (SV) detection. Yet, current alignment tools are not well suited for this. We present YAHA, a fast and flexible hash-based aligner. YAHA is as fast and accurate as BWA-SW at finding the single best alignment per query and is dramatically faster and more sensitive than both SSAHA2 and MegaBLAST at finding all possible alignments. Unlike other aligners that report all, or one, alignment per query, or that use simple heuristics to select alignments, YAHA uses a directed acyclic graph to find the optimal set of alignments that cover a query using a biologically relevant breakpoint penalty. YAHA can also report multiple mappings per defined segment of the query. We show that YAHA detects more breakpoints in less time than BWA-SW across all SV classes, and especially excels at complex SVs comprising multiple breakpoints. YAHA is currently supported on 64-bit Linux systems. Binaries and sample data are freely available for download from http://faculty.virginia.edu/irahall/YAHA. imh4y@virginia.edu.

Understanding Selective Downregulation of c-Myc Expression through Inhibition of General Transcription Regulators in Multiple Myeloma

DTIC Science & Technology

2014-06-01

AUTHOR(S) 5d. PROJECT NUMBER Dr. Charles Lin 5e. TASK NUMBER E-Mail: Charles_lin@dfci.harvard.edu 5f. WORK UNIT NUMBER 7...landscape of Multiple Myeloma (MM), this project has endeavored to provide an explanatory mechanism for how treatment with inhibitors of chromatin...category: 1472-1), BRD4 (Epitomics, category: 5716-1) or b-actin ( Sigma , clone AC-15, A5441). Data Analysis All ChIP-seq data sets were aligned using

The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures.

PubMed

Goldenberg, Ofir; Erez, Elana; Nimrod, Guy; Ben-Tal, Nir

2009-01-01

ConSurf-DB is a repository for evolutionary conservation analysis of the proteins of known structures in the Protein Data Bank (PDB). Sequence homologues of each of the PDB entries were collected and aligned using standard methods. The evolutionary conservation of each amino acid position in the alignment was calculated using the Rate4Site algorithm, implemented in the ConSurf web server. The algorithm takes into account the phylogenetic relations between the aligned proteins and the stochastic nature of the evolutionary process explicitly. Rate4Site assigns a conservation level for each position in the multiple sequence alignment using an empirical Bayesian inference. Visual inspection of the conservation patterns on the 3D structure often enables the identification of key residues that comprise the functionally important regions of the protein. The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il/

The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures

PubMed Central

Goldenberg, Ofir; Erez, Elana; Nimrod, Guy; Ben-Tal, Nir

2009-01-01

ConSurf-DB is a repository for evolutionary conservation analysis of the proteins of known structures in the Protein Data Bank (PDB). Sequence homologues of each of the PDB entries were collected and aligned using standard methods. The evolutionary conservation of each amino acid position in the alignment was calculated using the Rate4Site algorithm, implemented in the ConSurf web server. The algorithm takes into account the phylogenetic relations between the aligned proteins and the stochastic nature of the evolutionary process explicitly. Rate4Site assigns a conservation level for each position in the multiple sequence alignment using an empirical Bayesian inference. Visual inspection of the conservation patterns on the 3D structure often enables the identification of key residues that comprise the functionally important regions of the protein. The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il/ PMID:18971256

Solving the problem of Trans-Genomic Query with alignment tables.

PubMed

Parker, Douglass Stott; Hsiao, Ruey-Lung; Xing, Yi; Resch, Alissa M; Lee, Christopher J

2008-01-01

The trans-genomic query (TGQ) problem--enabling the free query of biological information, even across genomes--is a central challenge facing bioinformatics. Solutions to this problem can alter the nature of the field, moving it beyond the jungle of data integration and expanding the number and scope of questions that can be answered. An alignment table is a binary relationship on locations (sequence segments). An important special case of alignment tables are hit tables ? tables of pairs of highly similar segments produced by alignment tools like BLAST. However, alignment tables also include general binary relationships, and can represent any useful connection between sequence locations. They can be curated, and provide a high-quality queryable backbone of connections between biological information. Alignment tables thus can be a natural foundation for TGQ, as they permit a central part of the TGQ problem to be reduced to purely technical problems involving tables of locations.Key challenges in implementing alignment tables include efficient representation and indexing of sequence locations. We define a location datatype that can be incorporated naturally into common off-the-shelf database systems. We also describe an implementation of alignment tables in BLASTGRES, an extension of the open-source POSTGRESQL database system that provides indexing and operators on locations required for querying alignment tables. This paper also reviews several successful large-scale applications of alignment tables for Trans-Genomic Query. Tables with millions of alignments have been used in queries about alternative splicing, an area of genomic analysis concerning the way in which a single gene can yield multiple transcripts. Comparative genomics is a large potential application area for TGQ and alignment tables.

Structural phylogeny by profile extraction and multiple superimposition using electrostatic congruence as a discriminator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, Sandeep; Rao, Basuthkar J.; Baker, Nathan A.

2013-04-01

Phylogenetic analysis of proteins using multiple sequence alignment (MSA) assumes an underlying evolutionary relationship in these proteins which occasionally remains undetected due to considerable sequence divergence. Structural alignment programs have been developed to unravel such fuzzy relationships. However, none of these structure based methods have used electrostatic properties to discriminate between spatially equivalent residues. We present a methodology for MSA of a set of related proteins with known structures using electrostatic properties as an additional discriminator (STEEP). STEEP first extracts a profile, then generates a multiple structural superimposition providing a consolidated spatial framework for comparing residues and finally emits themore » MSA. Residues that are aligned differently by including or excluding electrostatic properties can be targeted by directed evolution experiments to transform the enzymatic properties of one protein into another. We have compared STEEP results to those obtained from a MSA program (ClustalW) and a structural alignment method (MUSTANG) for chymotrypsin serine proteases. Subsequently, we used PhyML to generate phylogenetic trees for the serine and metallo-β-lactamase superfamilies from the STEEP generated MSA, and corroborated the accepted relationships in these superfamilies. We have observed that STEEP acts as a functional classifier when electrostatic congruence is used as a discriminator, and thus identifies potential targets for directed evolution experiments. In summary, STEEP is unique among phylogenetic methods for its ability to use electrostatic congruence to specify mutations that might be the source of the functional divergence in a protein family. Based on our results, we also hypothesize that the active site and its close vicinity contains enough information to infer the correct phylogeny for related proteins.« less

ExprAlign - the identification of ESTs in non-model species by alignment of cDNA microarray expression profiles

PubMed Central

2009-01-01

Background Sequence identification of ESTs from non-model species offers distinct challenges particularly when these species have duplicated genomes and when they are phylogenetically distant from sequenced model organisms. For the common carp, an environmental model of aquacultural interest, large numbers of ESTs remained unidentified using BLAST sequence alignment. We have used the expression profiles from large-scale microarray experiments to suggest gene identities. Results Expression profiles from ~700 cDNA microarrays describing responses of 7 major tissues to multiple environmental stressors were used to define a co-expression landscape. This was based on the Pearsons correlation coefficient relating each gene with all other genes, from which a network description provided clusters of highly correlated genes as 'mountains'. We show that these contain genes with known identities and genes with unknown identities, and that the correlation constitutes evidence of identity in the latter. This procedure has suggested identities to 522 of 2701 unknown carp ESTs sequences. We also discriminate several common carp genes and gene isoforms that were not discriminated by BLAST sequence alignment alone. Precision in identification was substantially improved by use of data from multiple tissues and treatments. Conclusion The detailed analysis of co-expression landscapes is a sensitive technique for suggesting an identity for the large number of BLAST unidentified cDNAs generated in EST projects. It is capable of detecting even subtle changes in expression profiles, and thereby of distinguishing genes with a common BLAST identity into different identities. It benefits from the use of multiple treatments or contrasts, and from the large-scale microarray data. PMID:19939286

Design of multiple sequence alignment algorithms on parallel, distributed memory supercomputers.

PubMed

Church, Philip C; Goscinski, Andrzej; Holt, Kathryn; Inouye, Michael; Ghoting, Amol; Makarychev, Konstantin; Reumann, Matthias

2011-01-01

The challenge of comparing two or more genomes that have undergone recombination and substantial amounts of segmental loss and gain has recently been addressed for small numbers of genomes. However, datasets of hundreds of genomes are now common and their sizes will only increase in the future. Multiple sequence alignment of hundreds of genomes remains an intractable problem due to quadratic increases in compute time and memory footprint. To date, most alignment algorithms are designed for commodity clusters without parallelism. Hence, we propose the design of a multiple sequence alignment algorithm on massively parallel, distributed memory supercomputers to enable research into comparative genomics on large data sets. Following the methodology of the sequential progressiveMauve algorithm, we design data structures including sequences and sorted k-mer lists on the IBM Blue Gene/P supercomputer (BG/P). Preliminary results show that we can reduce the memory footprint so that we can potentially align over 250 bacterial genomes on a single BG/P compute node. We verify our results on a dataset of E.coli, Shigella and S.pneumoniae genomes. Our implementation returns results matching those of the original algorithm but in 1/2 the time and with 1/4 the memory footprint for scaffold building. In this study, we have laid the basis for multiple sequence alignment of large-scale datasets on a massively parallel, distributed memory supercomputer, thus enabling comparison of hundreds instead of a few genome sequences within reasonable time.

Self-aligned quadruple patterning using spacer on spacer integration optimization for N5

NASA Astrophysics Data System (ADS)

Thibaut, Sophie; Raley, Angélique; Mohanty, Nihar; Kal, Subhadeep; Liu, Eric; Ko, Akiteru; O'Meara, David; Tapily, Kandabara; Biolsi, Peter

2017-04-01

To meet scaling requirements, the semiconductor industry has extended 193nm immersion lithography beyond its minimum pitch limitation using multiple patterning schemes such as self-aligned double patterning, self-aligned quadruple patterning and litho-etch / litho etch iterations. Those techniques have been declined in numerous options in the last few years. Spacer on spacer pitch splitting integration has been proven to show multiple advantages compared to conventional pitch splitting approach. Reducing the number of pattern transfer steps associated with sacrificial layers resulted in significant decrease of cost and an overall simplification of the double pitch split technique. While demonstrating attractive aspects, SAQP spacer on spacer flow brings challenges of its own. Namely, material set selections and etch chemistry development for adequate selectivities, mandrel shape and spacer shape engineering to improve edge placement error (EPE). In this paper we follow up and extend upon our previous learning and proceed into more details on the robustness of the integration in regards to final pattern transfer and full wafer critical dimension uniformity. Furthermore, since the number of intermediate steps is reduced, one will expect improved uniformity and pitch walking control. This assertion will be verified through a thorough pitch walking analysis.

Prediction of β-turns in proteins from multiple alignment using neural network

PubMed Central

Kaur, Harpreet; Raghava, Gajendra Pal Singh

2003-01-01

A neural network-based method has been developed for the prediction of β-turns in proteins by using multiple sequence alignment. Two feed-forward back-propagation networks with a single hidden layer are used where the first-sequence structure network is trained with the multiple sequence alignment in the form of PSI-BLAST–generated position-specific scoring matrices. The initial predictions from the first network and PSIPRED-predicted secondary structure are used as input to the second structure-structure network to refine the predictions obtained from the first net. A significant improvement in prediction accuracy has been achieved by using evolutionary information contained in the multiple sequence alignment. The final network yields an overall prediction accuracy of 75.5% when tested by sevenfold cross-validation on a set of 426 nonhomologous protein chains. The corresponding Qpred, Qobs, and Matthews correlation coefficient values are 49.8%, 72.3%, and 0.43, respectively, and are the best among all the previously published β-turn prediction methods. The Web server BetaTPred2 (http://www.imtech.res.in/raghava/betatpred2/) has been developed based on this approach. PMID:12592033

CAB-Align: A Flexible Protein Structure Alignment Method Based on the Residue-Residue Contact Area.

PubMed

Terashi, Genki; Takeda-Shitaka, Mayuko

2015-01-01

Proteins are flexible, and this flexibility has an essential functional role. Flexibility can be observed in loop regions, rearrangements between secondary structure elements, and conformational changes between entire domains. However, most protein structure alignment methods treat protein structures as rigid bodies. Thus, these methods fail to identify the equivalences of residue pairs in regions with flexibility. In this study, we considered that the evolutionary relationship between proteins corresponds directly to the residue-residue physical contacts rather than the three-dimensional (3D) coordinates of proteins. Thus, we developed a new protein structure alignment method, contact area-based alignment (CAB-align), which uses the residue-residue contact area to identify regions of similarity. The main purpose of CAB-align is to identify homologous relationships at the residue level between related protein structures. The CAB-align procedure comprises two main steps: First, a rigid-body alignment method based on local and global 3D structure superposition is employed to generate a sufficient number of initial alignments. Then, iterative dynamic programming is executed to find the optimal alignment. We evaluated the performance and advantages of CAB-align based on four main points: (1) agreement with the gold standard alignment, (2) alignment quality based on an evolutionary relationship without 3D coordinate superposition, (3) consistency of the multiple alignments, and (4) classification agreement with the gold standard classification. Comparisons of CAB-align with other state-of-the-art protein structure alignment methods (TM-align, FATCAT, and DaliLite) using our benchmark dataset showed that CAB-align performed robustly in obtaining high-quality alignments and generating consistent multiple alignments with high coverage and accuracy rates, and it performed extremely well when discriminating between homologous and nonhomologous pairs of proteins in both single and multi-domain comparisons. The CAB-align software is freely available to academic users as stand-alone software at http://www.pharm.kitasato-u.ac.jp/bmd/bmd/Publications.html.

Inter-trial alignment of EEG data and phase-locking

NASA Astrophysics Data System (ADS)

Testorf, M. E.; Horak, P.; Connolly, A.; Holmes, G. L.; Jobst, B. C.

2015-09-01

Neuro-scientific studies are often aimed at imaging brain activity, which is time-locked to external stimuli. This provides the possibility to use statistical methods to extract even weak signal components, which occur with each stimulus. For electroencephalographic recordings this concept is limited by inevitable time jitter, which cannot be controlled in all cases. Our study is based on a cross-correlation analysis of trials to alignment trials based on the recorded data. This is demonstrated both with simulated signals and with clinical EEG data, which were recorded intracranially. Special attention is given to the evaluation of the time-frequency resolved phase-locking across multiple trails.

Is multiple-sequence alignment required for accurate inference of phylogeny?

PubMed

Höhl, Michael; Ragan, Mark A

2007-04-01

The process of inferring phylogenetic trees from molecular sequences almost always starts with a multiple alignment of these sequences but can also be based on methods that do not involve multiple sequence alignment. Very little is known about the accuracy with which such alignment-free methods recover the correct phylogeny or about the potential for increasing their accuracy. We conducted a large-scale comparison of ten alignment-free methods, among them one new approach that does not calculate distances and a faster variant of our pattern-based approach; all distance-based alignment-free methods are freely available from http://www.bioinformatics.org.au (as Python package decaf+py). We show that most methods exhibit a higher overall reconstruction accuracy in the presence of high among-site rate variation. Under all conditions that we considered, variants of the pattern-based approach were significantly better than the other alignment-free methods. The new pattern-based variant achieved a speed-up of an order of magnitude in the distance calculation step, accompanied by a small loss of tree reconstruction accuracy. A method of Bayesian inference from k-mers did not improve on classical alignment-free (and distance-based) methods but may still offer other advantages due to its Bayesian nature. We found the optimal word length k of word-based methods to be stable across various data sets, and we provide parameter ranges for two different alphabets. The influence of these alphabets was analyzed to reveal a trade-off in reconstruction accuracy between long and short branches. We have mapped the phylogenetic accuracy for many alignment-free methods, among them several recently introduced ones, and increased our understanding of their behavior in response to biologically important parameters. In all experiments, the pattern-based approach emerged as superior, at the expense of higher resource consumption. Nonetheless, no alignment-free method that we examined recovers the correct phylogeny as accurately as does an approach based on maximum-likelihood distance estimates of multiply aligned sequences.

SATe-II: very fast and accurate simultaneous estimation of multiple sequence alignments and phylogenetic trees.

PubMed

Liu, Kevin; Warnow, Tandy J; Holder, Mark T; Nelesen, Serita M; Yu, Jiaye; Stamatakis, Alexandros P; Linder, C Randal

2012-01-01

Highly accurate estimation of phylogenetic trees for large data sets is difficult, in part because multiple sequence alignments must be accurate for phylogeny estimation methods to be accurate. Coestimation of alignments and trees has been attempted but currently only SATé estimates reasonably accurate trees and alignments for large data sets in practical time frames (Liu K., Raghavan S., Nelesen S., Linder C.R., Warnow T. 2009b. Rapid and accurate large-scale coestimation of sequence alignments and phylogenetic trees. Science. 324:1561-1564). Here, we present a modification to the original SATé algorithm that improves upon SATé (which we now call SATé-I) in terms of speed and of phylogenetic and alignment accuracy. SATé-II uses a different divide-and-conquer strategy than SATé-I and so produces smaller more closely related subsets than SATé-I; as a result, SATé-II produces more accurate alignments and trees, can analyze larger data sets, and runs more efficiently than SATé-I. Generally, SATé is a metamethod that takes an existing multiple sequence alignment method as an input parameter and boosts the quality of that alignment method. SATé-II-boosted alignment methods are significantly more accurate than their unboosted versions, and trees based upon these improved alignments are more accurate than trees based upon the original alignments. Because SATé-I used maximum likelihood (ML) methods that treat gaps as missing data to estimate trees and because we found a correlation between the quality of tree/alignment pairs and ML scores, we explored the degree to which SATé's performance depends on using ML with gaps treated as missing data to determine the best tree/alignment pair. We present two lines of evidence that using ML with gaps treated as missing data to optimize the alignment and tree produces very poor results. First, we show that the optimization problem where a set of unaligned DNA sequences is given and the output is the tree and alignment of those sequences that maximize likelihood under the Jukes-Cantor model is uninformative in the worst possible sense. For all inputs, all trees optimize the likelihood score. Second, we show that a greedy heuristic that uses GTR+Gamma ML to optimize the alignment and the tree can produce very poor alignments and trees. Therefore, the excellent performance of SATé-II and SATé-I is not because ML is used as an optimization criterion for choosing the best tree/alignment pair but rather due to the particular divide-and-conquer realignment techniques employed.

Protein Sectors: Statistical Coupling Analysis versus Conservation

PubMed Central

Teşileanu, Tiberiu; Colwell, Lucy J.; Leibler, Stanislas

2015-01-01

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed “sectors”. The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation. It has been asserted that the protein sectors identified by SCA are functionally significant, with different sectors controlling different biochemical properties of the protein. Here we reconsider the available experimental data and note that it involves almost exclusively proteins with a single sector. We show that in this case sequence conservation is the dominating factor in SCA, and can alone be used to make statistically equivalent functional predictions. Therefore, we suggest shifting the experimental focus to proteins for which SCA identifies several sectors. Correlations in protein alignments, which have been shown to be informative in a number of independent studies, would then be less dominated by sequence conservation. PMID:25723535

NetCoffee: a fast and accurate global alignment approach to identify functionally conserved proteins in multiple networks.

PubMed

Hu, Jialu; Kehr, Birte; Reinert, Knut

2014-02-15

Owing to recent advancements in high-throughput technologies, protein-protein interaction networks of more and more species become available in public databases. The question of how to identify functionally conserved proteins across species attracts a lot of attention in computational biology. Network alignments provide a systematic way to solve this problem. However, most existing alignment tools encounter limitations in tackling this problem. Therefore, the demand for faster and more efficient alignment tools is growing. We present a fast and accurate algorithm, NetCoffee, which allows to find a global alignment of multiple protein-protein interaction networks. NetCoffee searches for a global alignment by maximizing a target function using simulated annealing on a set of weighted bipartite graphs that are constructed using a triplet approach similar to T-Coffee. To assess its performance, NetCoffee was applied to four real datasets. Our results suggest that NetCoffee remedies several limitations of previous algorithms, outperforms all existing alignment tools in terms of speed and nevertheless identifies biologically meaningful alignments. The source code and data are freely available for download under the GNU GPL v3 license at https://code.google.com/p/netcoffee/.

ExScalibur: A High-Performance Cloud-Enabled Suite for Whole Exome Germline and Somatic Mutation Identification

PubMed Central

Huang, Lei; Kang, Wenjun; Bartom, Elizabeth; Onel, Kenan; Volchenboum, Samuel; Andrade, Jorge

2015-01-01

Whole exome sequencing has facilitated the discovery of causal genetic variants associated with human diseases at deep coverage and low cost. In particular, the detection of somatic mutations from tumor/normal pairs has provided insights into the cancer genome. Although there is an abundance of publicly-available software for the detection of germline and somatic variants, concordance is generally limited among variant callers and alignment algorithms. Successful integration of variants detected by multiple methods requires in-depth knowledge of the software, access to high-performance computing resources, and advanced programming techniques. We present ExScalibur, a set of fully automated, highly scalable and modulated pipelines for whole exome data analysis. The suite integrates multiple alignment and variant calling algorithms for the accurate detection of germline and somatic mutations with close to 99% sensitivity and specificity. ExScalibur implements streamlined execution of analytical modules, real-time monitoring of pipeline progress, robust handling of errors and intuitive documentation that allows for increased reproducibility and sharing of results and workflows. It runs on local computers, high-performance computing clusters and cloud environments. In addition, we provide a data analysis report utility to facilitate visualization of the results that offers interactive exploration of quality control files, read alignment and variant calls, assisting downstream customization of potential disease-causing mutations. ExScalibur is open-source and is also available as a public image on Amazon cloud. PMID:26271043

Protein contact prediction by integrating deep multiple sequence alignments, coevolution and machine learning.

PubMed

Adhikari, Badri; Hou, Jie; Cheng, Jianlin

2018-03-01

In this study, we report the evaluation of the residue-residue contacts predicted by our three different methods in the CASP12 experiment, focusing on studying the impact of multiple sequence alignment, residue coevolution, and machine learning on contact prediction. The first method (MULTICOM-NOVEL) uses only traditional features (sequence profile, secondary structure, and solvent accessibility) with deep learning to predict contacts and serves as a baseline. The second method (MULTICOM-CONSTRUCT) uses our new alignment algorithm to generate deep multiple sequence alignment to derive coevolution-based features, which are integrated by a neural network method to predict contacts. The third method (MULTICOM-CLUSTER) is a consensus combination of the predictions of the first two methods. We evaluated our methods on 94 CASP12 domains. On a subset of 38 free-modeling domains, our methods achieved an average precision of up to 41.7% for top L/5 long-range contact predictions. The comparison of the three methods shows that the quality and effective depth of multiple sequence alignments, coevolution-based features, and machine learning integration of coevolution-based features and traditional features drive the quality of predicted protein contacts. On the full CASP12 dataset, the coevolution-based features alone can improve the average precision from 28.4% to 41.6%, and the machine learning integration of all the features further raises the precision to 56.3%, when top L/5 predicted long-range contacts are evaluated. And the correlation between the precision of contact prediction and the logarithm of the number of effective sequences in alignments is 0.66. © 2017 Wiley Periodicals, Inc.

High-throughput sequence alignment using Graphics Processing Units

PubMed Central

Schatz, Michael C; Trapnell, Cole; Delcher, Arthur L; Varshney, Amitabh

2007-01-01

Background The recent availability of new, less expensive high-throughput DNA sequencing technologies has yielded a dramatic increase in the volume of sequence data that must be analyzed. These data are being generated for several purposes, including genotyping, genome resequencing, metagenomics, and de novo genome assembly projects. Sequence alignment programs such as MUMmer have proven essential for analysis of these data, but researchers will need ever faster, high-throughput alignment tools running on inexpensive hardware to keep up with new sequence technologies. Results This paper describes MUMmerGPU, an open-source high-throughput parallel pairwise local sequence alignment program that runs on commodity Graphics Processing Units (GPUs) in common workstations. MUMmerGPU uses the new Compute Unified Device Architecture (CUDA) from nVidia to align multiple query sequences against a single reference sequence stored as a suffix tree. By processing the queries in parallel on the highly parallel graphics card, MUMmerGPU achieves more than a 10-fold speedup over a serial CPU version of the sequence alignment kernel, and outperforms the exact alignment component of MUMmer on a high end CPU by 3.5-fold in total application time when aligning reads from recent sequencing projects using Solexa/Illumina, 454, and Sanger sequencing technologies. Conclusion MUMmerGPU is a low cost, ultra-fast sequence alignment program designed to handle the increasing volume of data produced by new, high-throughput sequencing technologies. MUMmerGPU demonstrates that even memory-intensive applications can run significantly faster on the relatively low-cost GPU than on the CPU. PMID:18070356

MUSCLE: multiple sequence alignment with high accuracy and high throughput.

PubMed

Edgar, Robert C

2004-01-01

We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.

Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains.

PubMed Central

Sivasankar, S; Gumbiner, B; Leckband, D

2001-01-01

Direct measurements of the interactions between antiparallel, oriented monolayers of the complete extracellular region of C-cadherin demonstrate that, rather than binding in a single unique orientation, the cadherins adhere in three distinct alignments. The strongest adhesion is observed when the opposing extracellular fragments are completely interdigitated. A second adhesive alignment forms when the interdigitated proteins separate by 70 +/- 10 A. A third complex forms at a bilayer separation commensurate with the approximate overlap of cadherin extracellular domains 1 and 2 (CEC1-2). The locations of the energy minima are independent of both the surface density of bound cadherin and the stiffness of the force transducer. Using surface element integration, we show that two flat surfaces that interact through an oscillatory potential will exhibit discrete minima at the same locations in the force profile measured between hemicylinders covered with identical materials. The measured interaction profiles, therefore, reflect the relative separations at which the antiparallel proteins adhere, and are unaffected by the curvature of the underlying substrate. The successive formation and rupture of multiple protein contacts during detachment can explain the observed sluggish unbinding of cadherin monolayers. Velocity-distance profiles, obtained by quantitative video analysis of the unbinding trajectory, exhibit three velocity regimes, the transitions between which coincide with the positions of the adhesive minima. These findings suggest that cadherins undergo multiple stage unbinding, which may function to impede adhesive failure under force. PMID:11259289

Designing universal primers for the isolation of DNA sequences encoding Proanthocyanidins biosynthetic enzymes in Crataegus aronia

PubMed Central

2012-01-01

Background Hawthorn is the common name of all plant species in the genus Crataegus, which belongs to the Rosaceae family. Crataegus are considered useful medicinal plants because of their high content of proanthocyanidins (PAs) and other related compounds. To improve PAs production in Crataegus tissues, the sequences of genes encoding PAs biosynthetic enzymes are required. Findings Different bioinformatics tools, including BLAST, multiple sequence alignment and alignment PCR analysis were used to design primers suitable for the amplification of DNA fragments from 10 candidate genes encoding enzymes involved in PAs biosynthesis in C. aronia. DNA sequencing results proved the utility of the designed primers. The primers were used successfully to amplify DNA fragments of different PAs biosynthesis genes in different Rosaceae plants. Conclusion To the best of our knowledge, this is the first use of the alignment PCR approach to isolate DNA sequences encoding PAs biosynthetic enzymes in Rosaceae plants. PMID:22883984

Designing universal primers for the isolation of DNA sequences encoding Proanthocyanidins biosynthetic enzymes in Crataegus aronia.

PubMed

Zuiter, Afnan Saeid; Sawwan, Jammal; Al Abdallat, Ayed

2012-08-10

Hawthorn is the common name of all plant species in the genus Crataegus, which belongs to the Rosaceae family. Crataegus are considered useful medicinal plants because of their high content of proanthocyanidins (PAs) and other related compounds. To improve PAs production in Crataegus tissues, the sequences of genes encoding PAs biosynthetic enzymes are required. Different bioinformatics tools, including BLAST, multiple sequence alignment and alignment PCR analysis were used to design primers suitable for the amplification of DNA fragments from 10 candidate genes encoding enzymes involved in PAs biosynthesis in C. aronia. DNA sequencing results proved the utility of the designed primers. The primers were used successfully to amplify DNA fragments of different PAs biosynthesis genes in different Rosaceae plants. To the best of our knowledge, this is the first use of the alignment PCR approach to isolate DNA sequences encoding PAs biosynthetic enzymes in Rosaceae plants.

Biclustering as a method for RNA local multiple sequence alignment.

PubMed

Wang, Shu; Gutell, Robin R; Miranker, Daniel P

2007-12-15

Biclustering is a clustering method that simultaneously clusters both the domain and range of a relation. A challenge in multiple sequence alignment (MSA) is that the alignment of sequences is often intended to reveal groups of conserved functional subsequences. Simultaneously, the grouping of the sequences can impact the alignment; precisely the kind of dual situation biclustering is intended to address. We define a representation of the MSA problem enabling the application of biclustering algorithms. We develop a computer program for local MSA, BlockMSA, that combines biclustering with divide-and-conquer. BlockMSA simultaneously finds groups of similar sequences and locally aligns subsequences within them. Further alignment is accomplished by dividing both the set of sequences and their contents. The net result is both a multiple sequence alignment and a hierarchical clustering of the sequences. BlockMSA was tested on the subsets of the BRAliBase 2.1 benchmark suite that display high variability and on an extension to that suite to larger problem sizes. Also, alignments were evaluated of two large datasets of current biological interest, T box sequences and Group IC1 Introns. The results were compared with alignments computed by ClustalW, MAFFT, MUCLE and PROBCONS alignment programs using Sum of Pairs (SPS) and Consensus Count. Results for the benchmark suite are sensitive to problem size. On problems of 15 or greater sequences, BlockMSA is consistently the best. On none of the problems in the test suite are there appreciable differences in scores among BlockMSA, MAFFT and PROBCONS. On the T box sequences, BlockMSA does the most faithful job of reproducing known annotations. MAFFT and PROBCONS do not. On the Intron sequences, BlockMSA, MAFFT and MUSCLE are comparable at identifying conserved regions. BlockMSA is implemented in Java. Source code and supplementary datasets are available at http://aug.csres.utexas.edu/msa/

Vertical decomposition with Genetic Algorithm for Multiple Sequence Alignment

PubMed Central

2011-01-01

Background Many Bioinformatics studies begin with a multiple sequence alignment as the foundation for their research. This is because multiple sequence alignment can be a useful technique for studying molecular evolution and analyzing sequence structure relationships. Results In this paper, we have proposed a Vertical Decomposition with Genetic Algorithm (VDGA) for Multiple Sequence Alignment (MSA). In VDGA, we divide the sequences vertically into two or more subsequences, and then solve them individually using a guide tree approach. Finally, we combine all the subsequences to generate a new multiple sequence alignment. This technique is applied on the solutions of the initial generation and of each child generation within VDGA. We have used two mechanisms to generate an initial population in this research: the first mechanism is to generate guide trees with randomly selected sequences and the second is shuffling the sequences inside such trees. Two different genetic operators have been implemented with VDGA. To test the performance of our algorithm, we have compared it with existing well-known methods, namely PRRP, CLUSTALX, DIALIGN, HMMT, SB_PIMA, ML_PIMA, MULTALIGN, and PILEUP8, and also other methods, based on Genetic Algorithms (GA), such as SAGA, MSA-GA and RBT-GA, by solving a number of benchmark datasets from BAliBase 2.0. Conclusions The experimental results showed that the VDGA with three vertical divisions was the most successful variant for most of the test cases in comparison to other divisions considered with VDGA. The experimental results also confirmed that VDGA outperformed the other methods considered in this research. PMID:21867510

Reliability of lower limb alignment measures using an established landmark-based method with a customized computer software program

PubMed Central

Sled, Elizabeth A.; Sheehy, Lisa M.; Felson, David T.; Costigan, Patrick A.; Lam, Miu; Cooke, T. Derek V.

2010-01-01

The objective of the study was to evaluate the reliability of frontal plane lower limb alignment measures using a landmark-based method by (1) comparing inter- and intra-reader reliability between measurements of alignment obtained manually with those using a computer program, and (2) determining inter- and intra-reader reliability of computer-assisted alignment measures from full-limb radiographs. An established method for measuring alignment was used, involving selection of 10 femoral and tibial bone landmarks. 1) To compare manual and computer methods, we used digital images and matching paper copies of five alignment patterns simulating healthy and malaligned limbs drawn using AutoCAD. Seven readers were trained in each system. Paper copies were measured manually and repeat measurements were performed daily for 3 days, followed by a similar routine with the digital images using the computer. 2) To examine the reliability of computer-assisted measures from full-limb radiographs, 100 images (200 limbs) were selected as a random sample from 1,500 full-limb digital radiographs which were part of the Multicenter Osteoarthritis (MOST) Study. Three trained readers used the software program to measure alignment twice from the batch of 100 images, with two or more weeks between batch handling. Manual and computer measures of alignment showed excellent agreement (intraclass correlations [ICCs] 0.977 – 0.999 for computer analysis; 0.820 – 0.995 for manual measures). The computer program applied to full-limb radiographs produced alignment measurements with high inter- and intra-reader reliability (ICCs 0.839 – 0.998). In conclusion, alignment measures using a bone landmark-based approach and a computer program were highly reliable between multiple readers. PMID:19882339

From Principal Component to Direct Coupling Analysis of Coevolution in Proteins: Low-Eigenvalue Modes are Needed for Structure Prediction

PubMed Central

Cocco, Simona; Monasson, Remi; Weigt, Martin

2013-01-01

Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the most correlated groups of residues, and direct coupling analysis (DCA), a global inference method based on the maximum entropy principle, which aims at predicting residue-residue contacts. In this paper, inspired by the statistical physics of disordered systems, we introduce the Hopfield-Potts model to naturally interpolate between these two approaches. The Hopfield-Potts model allows us to identify relevant ‘patterns’ of residues from the knowledge of the eigenmodes and eigenvalues of the residue-residue correlation matrix. We show how the computation of such statistical patterns makes it possible to accurately predict residue-residue contacts with a much smaller number of parameters than DCA. This dimensional reduction allows us to avoid overfitting and to extract contact information from multiple-sequence alignments of reduced size. In addition, we show that low-eigenvalue correlation modes, discarded by PCA, are important to recover structural information: the corresponding patterns are highly localized, that is, they are concentrated in few sites, which we find to be in close contact in the three-dimensional protein fold. PMID:23990764

Multi-resolution Shape Analysis via Non-Euclidean Wavelets: Applications to Mesh Segmentation and Surface Alignment Problems.

PubMed

Kim, Won Hwa; Chung, Moo K; Singh, Vikas

2013-01-01

The analysis of 3-D shape meshes is a fundamental problem in computer vision, graphics, and medical imaging. Frequently, the needs of the application require that our analysis take a multi-resolution view of the shape's local and global topology, and that the solution is consistent across multiple scales. Unfortunately, the preferred mathematical construct which offers this behavior in classical image/signal processing, Wavelets, is no longer applicable in this general setting (data with non-uniform topology). In particular, the traditional definition does not allow writing out an expansion for graphs that do not correspond to the uniformly sampled lattice (e.g., images). In this paper, we adapt recent results in harmonic analysis, to derive Non-Euclidean Wavelets based algorithms for a range of shape analysis problems in vision and medical imaging. We show how descriptors derived from the dual domain representation offer native multi-resolution behavior for characterizing local/global topology around vertices. With only minor modifications, the framework yields a method for extracting interest/key points from shapes, a surprisingly simple algorithm for 3-D shape segmentation (competitive with state of the art), and a method for surface alignment (without landmarks). We give an extensive set of comparison results on a large shape segmentation benchmark and derive a uniqueness theorem for the surface alignment problem.

Rail-RNA: scalable analysis of RNA-seq splicing and coverage.

PubMed

Nellore, Abhinav; Collado-Torres, Leonardo; Jaffe, Andrew E; Alquicira-Hernández, José; Wilks, Christopher; Pritt, Jacob; Morton, James; Leek, Jeffrey T; Langmead, Ben

2017-12-15

RNA sequencing (RNA-seq) experiments now span hundreds to thousands of samples. Current spliced alignment software is designed to analyze each sample separately. Consequently, no information is gained from analyzing multiple samples together, and it requires extra work to obtain analysis products that incorporate data from across samples. We describe Rail-RNA, a cloud-enabled spliced aligner that analyzes many samples at once. Rail-RNA eliminates redundant work across samples, making it more efficient as samples are added. For many samples, Rail-RNA is more accurate than annotation-assisted aligners. We use Rail-RNA to align 667 RNA-seq samples from the GEUVADIS project on Amazon Web Services in under 16 h for US$0.91 per sample. Rail-RNA outputs alignments in SAM/BAM format; but it also outputs (i) base-level coverage bigWigs for each sample; (ii) coverage bigWigs encoding normalized mean and median coverages at each base across samples analyzed; and (iii) exon-exon splice junctions and indels (features) in columnar formats that juxtapose coverages in samples in which a given feature is found. Supplementary outputs are ready for use with downstream packages for reproducible statistical analysis. We use Rail-RNA to identify expressed regions in the GEUVADIS samples and show that both annotated and unannotated (novel) expressed regions exhibit consistent patterns of variation across populations and with respect to known confounding variables. Rail-RNA is open-source software available at http://rail.bio. anellore@gmail.com or langmea@cs.jhu.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Accuracy Estimation and Parameter Advising for Protein Multiple Sequence Alignment

PubMed Central

DeBlasio, Dan

2013-01-01

Abstract We develop a novel and general approach to estimating the accuracy of multiple sequence alignments without knowledge of a reference alignment, and use our approach to address a new task that we call parameter advising: the problem of choosing values for alignment scoring function parameters from a given set of choices to maximize the accuracy of a computed alignment. For protein alignments, we consider twelve independent features that contribute to a quality alignment. An accuracy estimator is learned that is a polynomial function of these features; its coefficients are determined by minimizing its error with respect to true accuracy using mathematical optimization. Compared to prior approaches for estimating accuracy, our new approach (a) introduces novel feature functions that measure nonlocal properties of an alignment yet are fast to evaluate, (b) considers more general classes of estimators beyond linear combinations of features, and (c) develops new regression formulations for learning an estimator from examples; in addition, for parameter advising, we (d) determine the optimal parameter set of a given cardinality, which specifies the best parameter values from which to choose. Our estimator, which we call Facet (for “feature-based accuracy estimator”), yields a parameter advisor that on the hardest benchmarks provides more than a 27% improvement in accuracy over the best default parameter choice, and for parameter advising significantly outperforms the best prior approaches to assessing alignment quality. PMID:23489379

GibbsCluster: unsupervised clustering and alignment of peptide sequences.

PubMed

Andreatta, Massimo; Alvarez, Bruno; Nielsen, Morten

2017-07-03

Receptor interactions with short linear peptide fragments (ligands) are at the base of many biological signaling processes. Conserved and information-rich amino acid patterns, commonly called sequence motifs, shape and regulate these interactions. Because of the properties of a receptor-ligand system or of the assay used to interrogate it, experimental data often contain multiple sequence motifs. GibbsCluster is a powerful tool for unsupervised motif discovery because it can simultaneously cluster and align peptide data. The GibbsCluster 2.0 presented here is an improved version incorporating insertion and deletions accounting for variations in motif length in the peptide input. In basic terms, the program takes as input a set of peptide sequences and clusters them into meaningful groups. It returns the optimal number of clusters it identified, together with the sequence alignment and sequence motif characterizing each cluster. Several parameters are available to customize cluster analysis, including adjustable penalties for small clusters and overlapping groups and a trash cluster to remove outliers. As an example application, we used the server to deconvolute multiple specificities in large-scale peptidome data generated by mass spectrometry. The server is available at http://www.cbs.dtu.dk/services/GibbsCluster-2.0. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Using a color-coded ambigraphic nucleic acid notation to visualize conserved palindromic motifs within and across genomes

PubMed Central

2014-01-01

Background Ambiscript is a graphically-designed nucleic acid notation that uses symbol symmetries to support sequence complementation, highlight biologically-relevant palindromes, and facilitate the analysis of consensus sequences. Although the original Ambiscript notation was designed to easily represent consensus sequences for multiple sequence alignments, the notation’s black-on-white ambiguity characters are unable to reflect the statistical distribution of nucleotides found at each position. We now propose a color-augmented ambigraphic notation to encode the frequency of positional polymorphisms in these consensus sequences. Results We have implemented this color-coding approach by creating an Adobe Flash® application ( http://www.ambiscript.org) that shades and colors modified Ambiscript characters according to the prevalence of the encoded nucleotide at each position in the alignment. The resulting graphic helps viewers perceive biologically-relevant patterns in multiple sequence alignments by uniquely combining color, shading, and character symmetries to highlight palindromes and inverted repeats in conserved DNA motifs. Conclusion Juxtaposing an intuitive color scheme over the deliberate character symmetries of an ambigraphic nucleic acid notation yields a highly-functional nucleic acid notation that maximizes information content and successfully embodies key principles of graphic excellence put forth by the statistician and graphic design theorist, Edward Tufte. PMID:24447494

Automated image alignment for 2D gel electrophoresis in a high-throughput proteomics pipeline.

PubMed

Dowsey, Andrew W; Dunn, Michael J; Yang, Guang-Zhong

2008-04-01

The quest for high-throughput proteomics has revealed a number of challenges in recent years. Whilst substantial improvements in automated protein separation with liquid chromatography and mass spectrometry (LC/MS), aka 'shotgun' proteomics, have been achieved, large-scale open initiatives such as the Human Proteome Organization (HUPO) Brain Proteome Project have shown that maximal proteome coverage is only possible when LC/MS is complemented by 2D gel electrophoresis (2-DE) studies. Moreover, both separation methods require automated alignment and differential analysis to relieve the bioinformatics bottleneck and so make high-throughput protein biomarker discovery a reality. The purpose of this article is to describe a fully automatic image alignment framework for the integration of 2-DE into a high-throughput differential expression proteomics pipeline. The proposed method is based on robust automated image normalization (RAIN) to circumvent the drawbacks of traditional approaches. These use symbolic representation at the very early stages of the analysis, which introduces persistent errors due to inaccuracies in modelling and alignment. In RAIN, a third-order volume-invariant B-spline model is incorporated into a multi-resolution schema to correct for geometric and expression inhomogeneity at multiple scales. The normalized images can then be compared directly in the image domain for quantitative differential analysis. Through evaluation against an existing state-of-the-art method on real and synthetically warped 2D gels, the proposed analysis framework demonstrates substantial improvements in matching accuracy and differential sensitivity. High-throughput analysis is established through an accelerated GPGPU (general purpose computation on graphics cards) implementation. Supplementary material, software and images used in the validation are available at http://www.proteomegrid.org/rain/.

Information Compression, Multiple Alignment, and the Representation and Processing of Knowledge in the Brain

PubMed Central

Wolff, J. Gerard

2016-01-01

The SP theory of intelligence, with its realization in the SP computer model, aims to simplify and integrate observations and concepts across artificial intelligence, mainstream computing, mathematics, and human perception and cognition, with information compression as a unifying theme. This paper describes how abstract structures and processes in the theory may be realized in terms of neurons, their interconnections, and the transmission of signals between neurons. This part of the SP theory—SP-neural—is a tentative and partial model for the representation and processing of knowledge in the brain. Empirical support for the SP theory—outlined in the paper—provides indirect support for SP-neural. In the abstract part of the SP theory (SP-abstract), all kinds of knowledge are represented with patterns, where a pattern is an array of atomic symbols in one or two dimensions. In SP-neural, the concept of a “pattern” is realized as an array of neurons called a pattern assembly, similar to Hebb's concept of a “cell assembly” but with important differences. Central to the processing of information in SP-abstract is information compression via the matching and unification of patterns (ICMUP) and, more specifically, information compression via the powerful concept of multiple alignment, borrowed and adapted from bioinformatics. Processes such as pattern recognition, reasoning and problem solving are achieved via the building of multiple alignments, while unsupervised learning is achieved by creating patterns from sensory information and also by creating patterns from multiple alignments in which there is a partial match between one pattern and another. It is envisaged that, in SP-neural, short-lived neural structures equivalent to multiple alignments will be created via an inter-play of excitatory and inhibitory neural signals. It is also envisaged that unsupervised learning will be achieved by the creation of pattern assemblies from sensory information and from the neural equivalents of multiple alignments, much as in the non-neural SP theory—and significantly different from the “Hebbian” kinds of learning which are widely used in the kinds of artificial neural network that are popular in computer science. The paper discusses several associated issues, with relevant empirical evidence. PMID:27857695

Information Compression, Multiple Alignment, and the Representation and Processing of Knowledge in the Brain.

PubMed

Wolff, J Gerard

2016-01-01

The SP theory of intelligence , with its realization in the SP computer model , aims to simplify and integrate observations and concepts across artificial intelligence, mainstream computing, mathematics, and human perception and cognition, with information compression as a unifying theme. This paper describes how abstract structures and processes in the theory may be realized in terms of neurons, their interconnections, and the transmission of signals between neurons. This part of the SP theory- SP-neural -is a tentative and partial model for the representation and processing of knowledge in the brain. Empirical support for the SP theory-outlined in the paper-provides indirect support for SP-neural. In the abstract part of the SP theory (SP-abstract), all kinds of knowledge are represented with patterns , where a pattern is an array of atomic symbols in one or two dimensions. In SP-neural, the concept of a "pattern" is realized as an array of neurons called a pattern assembly , similar to Hebb's concept of a "cell assembly" but with important differences. Central to the processing of information in SP-abstract is information compression via the matching and unification of patterns (ICMUP) and, more specifically, information compression via the powerful concept of multiple alignment , borrowed and adapted from bioinformatics. Processes such as pattern recognition, reasoning and problem solving are achieved via the building of multiple alignments, while unsupervised learning is achieved by creating patterns from sensory information and also by creating patterns from multiple alignments in which there is a partial match between one pattern and another. It is envisaged that, in SP-neural, short-lived neural structures equivalent to multiple alignments will be created via an inter-play of excitatory and inhibitory neural signals. It is also envisaged that unsupervised learning will be achieved by the creation of pattern assemblies from sensory information and from the neural equivalents of multiple alignments, much as in the non-neural SP theory-and significantly different from the "Hebbian" kinds of learning which are widely used in the kinds of artificial neural network that are popular in computer science. The paper discusses several associated issues, with relevant empirical evidence.

[Genetic variants of the Crimean-Congo hemorrhagic fever virus circulating in endemic areas of the southern Tajikistan in 2009].

PubMed

Petrova, I D; Kononova, Iu V; Chausov, E V; Shestopalov, A M; Tishkova, F Kh

2013-01-01

506 Hyalomma anatolicum ticks were collected and assayed in two Crimean-Congo hemorrhagic fever (CCHF) endemic regions of Tajikistan. Antigen and RNA of CCHF virus were detected in 3.4% of tick pools from Rudaki district using ELISA and RT-PCR tests. As of Tursunzade district, viral antigen was identified in 9.0% of samples and viral RNA was identified in 8.1% of samples. The multiple alignment of the obtained nucleotide sequences of CCHF virus genome S-segment 287-nt region (996-1282) and multiple alignment of deduced amino acid sequences of the samples, carried out to compare with CCHF virus strains from the GenBank database, as well as phylogenetic analysis, enabled us to conclude that Asia 1 and Asia 2 genotypes of CCHF virus are circulating in Tajikistan. It is important to note that the genotype Asia 1 virus was detected for the first time in Tajikistan.

Introducing difference recurrence relations for faster semi-global alignment of long sequences.

PubMed

Suzuki, Hajime; Kasahara, Masahiro

2018-02-19

The read length of single-molecule DNA sequencers is reaching 1 Mb. Popular alignment software tools widely used for analyzing such long reads often take advantage of single-instruction multiple-data (SIMD) operations to accelerate calculation of dynamic programming (DP) matrices in the Smith-Waterman-Gotoh (SWG) algorithm with a fixed alignment start position at the origin. Nonetheless, 16-bit or 32-bit integers are necessary for storing the values in a DP matrix when sequences to be aligned are long; this situation hampers the use of the full SIMD width of modern processors. We proposed a faster semi-global alignment algorithm, "difference recurrence relations," that runs more rapidly than the state-of-the-art algorithm by a factor of 2.1. Instead of calculating and storing all the values in a DP matrix directly, our algorithm computes and stores mainly the differences between the values of adjacent cells in the matrix. Although the SWG algorithm and our algorithm can output exactly the same result, our algorithm mainly involves 8-bit integer operations, enabling us to exploit the full width of SIMD operations (e.g., 32) on modern processors. We also developed a library, libgaba, so that developers can easily integrate our algorithm into alignment programs. Our novel algorithm and optimized library implementation will facilitate accelerating nucleotide long-read analysis algorithms that use pairwise alignment stages. The library is implemented in the C programming language and available at https://github.com/ocxtal/libgaba .

Extrinsic Factors as Component Positions to Bone and Intrinsic Factors Affecting Postoperative Rotational Limb Alignment in Total Knee Arthroplasty.

PubMed

Mochizuki, Tomoharu; Sato, Takashi; Tanifuji, Osamu; Watanabe, Satoshi; Kobayashi, Koichi; Endo, Naoto

2018-02-13

This study aimed to identify the factors affecting postoperative rotational limb alignment of the tibia relative to the femur. We hypothesized that not only component positions but also several intrinsic factors were associated with postoperative rotational limb alignment. This study included 99 knees (90 women and 9 men) with a mean age of 77 ± 6 years. A three-dimensional (3D) assessment system was applied under weight-bearing conditions to biplanar long-leg radiographs using 3D-to-2D image registration technique. The evaluation parameters were (1) component position; (2) preoperative and postoperative coronal, sagittal, and rotational limb alignment; (3) preoperative bony deformity, including femoral torsion, condylar twist angle, and tibial torsion; and (4) preoperative and postoperative range of motion (ROM). In multiple linear regression analysis using a stepwise procedure, postoperative rotational limb alignment was associated with the following: (1) rotation of the component position (tibia: β = 0.371, P < .0001; femur: β = -0.327, P < .0001), (2) preoperative rotational limb alignment (β = 0.253, P = .001), (3) postoperative flexion angle (β = 0.195, P = .007), and (4) tibial torsion (β = 0.193, P = .010). In addition to component positions, the intrinsic factors, such as preoperative rotational limb alignment, ROM, and tibial torsion, affected postoperative rotational limb alignment. On a premise of correct component positions, the intrinsic factors that can be controlled by surgeons should be taken care. In particular, ROM is necessary to be improved within the possible range to acquire better postoperative rotational limb alignment. Copyright © 2018 Elsevier Inc. All rights reserved.

An intuitive graphical webserver for multiple-choice protein sequence search.

PubMed

Banky, Daniel; Szalkai, Balazs; Grolmusz, Vince

2014-04-10

Every day tens of thousands of sequence searches and sequence alignment queries are submitted to webservers. The capitalized word "BLAST" becomes a verb, describing the act of performing sequence search and alignment. However, if one needs to search for sequences that contain, for example, two hydrophobic and three polar residues at five given positions, the query formation on the most frequently used webservers will be difficult. Some servers support the formation of queries with regular expressions, but most of the users are unfamiliar with their syntax. Here we present an intuitive, easily applicable webserver, the Protein Sequence Analysis server, that allows the formation of multiple choice queries by simply drawing the residues to their positions; if more than one residue are drawn to the same position, then they will be nicely stacked on the user interface, indicating the multiple choice at the given position. This computer-game-like interface is natural and intuitive, and the coloring of the residues makes possible to form queries requiring not just certain amino acids in the given positions, but also small nonpolar, negatively charged, hydrophobic, positively charged, or polar ones. The webserver is available at http://psa.pitgroup.org. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular systematics of terraranas (Anura: Brachycephaloidea) with an assessment of the effects of alignment and optimality criteria.

PubMed

Padial, José M; Grant, Taran; Frost, Darrel R

2014-06-26

Brachycephaloidea is a monophyletic group of frogs with more than 1000 species distributed throughout the New World tropics, subtropics, and Andean regions. Recently, the group has been the target of multiple molecular phylogenetic analyses, resulting in extensive changes in its taxonomy. Here, we test previous hypotheses of phylogenetic relationships for the group by combining available molecular evidence (sequences of 22 genes representing 431 ingroup and 25 outgroup terminals) and performing a tree-alignment analysis under the parsimony optimality criterion using the program POY. To elucidate the effects of alignment and optimality criterion on phylogenetic inferences, we also used the program MAFFT to obtain a similarity-alignment for analysis under both parsimony and maximum likelihood using the programs TNT and GARLI, respectively. Although all three analytical approaches agreed on numerous points, there was also extensive disagreement. Tree-alignment under parsimony supported the monophyly of the ingroup and the sister group relationship of the monophyletic marsupial frogs (Hemiphractidae), while maximum likelihood and parsimony analyses of the MAFFT similarity-alignment did not. All three methods differed with respect to the position of Ceuthomantis smaragdinus (Ceuthomantidae), with tree-alignment using parsimony recovering this species as the sister of Pristimantis + Yunganastes. All analyses rejected the monophyly of Strabomantidae and Strabomantinae as originally defined, and the tree-alignment analysis under parsimony further rejected the recently redefined Craugastoridae and Pristimantinae. Despite the greater emphasis in the systematics literature placed on the choice of optimality criterion for evaluating trees than on the choice of method for aligning DNA sequences, we found that the topological differences attributable to the alignment method were as great as those caused by the optimality criterion. Further, the optimal tree-alignment indicates that insertions and deletions occurred in twice as many aligned positions as implied by the optimal similarity-alignment, confirming previous findings that sequence turnover through insertion and deletion events plays a greater role in molecular evolution than indicated by similarity-alignments. Our results also provide a clear empirical demonstration of the different effects of wildcard taxa produced by missing data in parsimony and maximum likelihood analyses. Specifically, maximum likelihood analyses consistently (81% bootstrap frequency) provided spurious resolution despite a lack of evidence, whereas parsimony correctly depicted the ambiguity due to missing data by collapsing unsupported nodes. We provide a new taxonomy for the group that retains previously recognized Linnaean taxa except for Ceuthomantidae, Strabomantidae, and Strabomantinae. A phenotypically diagnosable superfamily is recognized formally as Brachycephaloidea, with the informal, unranked name terrarana retained as the standard common name for these frogs. We recognize three families within Brachycephaloidea that are currently diagnosable solely on molecular grounds (Brachycephalidae, Craugastoridae, and Eleutherodactylidae), as well as five subfamilies (Craugastorinae, Eleutherodactylinae, Holoadeninae, Phyzelaphryninae, and Pristimantinae) corresponding in large part to previous families and subfamilies. Our analyses upheld the monophyly of all tested genera, but we found numerous subgeneric taxa to be non-monophyletic and modified the taxonomy accordingly.

Generic accelerated sequence alignment in SeqAn using vectorization and multi-threading.

PubMed

Rahn, René; Budach, Stefan; Costanza, Pascal; Ehrhardt, Marcel; Hancox, Jonny; Reinert, Knut

2018-05-03

Pairwise sequence alignment is undoubtedly a central tool in many bioinformatics analyses. In this paper, we present a generically accelerated module for pairwise sequence alignments applicable for a broad range of applications. In our module, we unified the standard dynamic programming kernel used for pairwise sequence alignments and extended it with a generalized inter-sequence vectorization layout, such that many alignments can be computed simultaneously by exploiting SIMD (Single Instruction Multiple Data) instructions of modern processors. We then extended the module by adding two layers of thread-level parallelization, where we a) distribute many independent alignments on multiple threads and b) inherently parallelize a single alignment computation using a work stealing approach producing a dynamic wavefront progressing along the minor diagonal. We evaluated our alignment vectorization and parallelization on different processors, including the newest Intel® Xeon® (Skylake) and Intel® Xeon Phi™ (KNL) processors, and use cases. The instruction set AVX512-BW (Byte and Word), available on Skylake processors, can genuinely improve the performance of vectorized alignments. We could run single alignments 1600 times faster on the Xeon Phi™ and 1400 times faster on the Xeon® than executing them with our previous sequential alignment module. The module is programmed in C++ using the SeqAn (Reinert et al., 2017) library and distributed with version 2.4. under the BSD license. We support SSE4, AVX2, AVX512 instructions and included UME::SIMD, a SIMD-instruction wrapper library, to extend our module for further instruction sets. We thoroughly test all alignment components with all major C++ compilers on various platforms. rene.rahn@fu-berlin.de.

Parametric and non-parametric masking of randomness in sequence alignments can be improved and leads to better resolved trees.

PubMed

Kück, Patrick; Meusemann, Karen; Dambach, Johannes; Thormann, Birthe; von Reumont, Björn M; Wägele, Johann W; Misof, Bernhard

2010-03-31

Methods of alignment masking, which refers to the technique of excluding alignment blocks prior to tree reconstructions, have been successful in improving the signal-to-noise ratio in sequence alignments. However, the lack of formally well defined methods to identify randomness in sequence alignments has prevented a routine application of alignment masking. In this study, we compared the effects on tree reconstructions of the most commonly used profiling method (GBLOCKS) which uses a predefined set of rules in combination with alignment masking, with a new profiling approach (ALISCORE) based on Monte Carlo resampling within a sliding window, using different data sets and alignment methods. While the GBLOCKS approach excludes variable sections above a certain threshold which choice is left arbitrary, the ALISCORE algorithm is free of a priori rating of parameter space and therefore more objective. ALISCORE was successfully extended to amino acids using a proportional model and empirical substitution matrices to score randomness in multiple sequence alignments. A complex bootstrap resampling leads to an even distribution of scores of randomly similar sequences to assess randomness of the observed sequence similarity. Testing performance on real data, both masking methods, GBLOCKS and ALISCORE, helped to improve tree resolution. The sliding window approach was less sensitive to different alignments of identical data sets and performed equally well on all data sets. Concurrently, ALISCORE is capable of dealing with different substitution patterns and heterogeneous base composition. ALISCORE and the most relaxed GBLOCKS gap parameter setting performed best on all data sets. Correspondingly, Neighbor-Net analyses showed the most decrease in conflict. Alignment masking improves signal-to-noise ratio in multiple sequence alignments prior to phylogenetic reconstruction. Given the robust performance of alignment profiling, alignment masking should routinely be used to improve tree reconstructions. Parametric methods of alignment profiling can be easily extended to more complex likelihood based models of sequence evolution which opens the possibility of further improvements.

Sex differences in knee joint loading: Cross-sectional study in geriatric population.

PubMed

Ro, Du Hyun; Lee, Dong Yeon; Moon, Giho; Lee, Sahnghoon; Seo, Sang Gyo; Kim, Seong Hwan; Park, In Woong; Lee, Myung Chul

2017-06-01

This study investigated sex differences in knee biomechanics and investigated determinants for difference in a geriatric population. Age-matched healthy volunteers (42 males and 42 females, average age 65 years) without knee OA were included in the study. Subjects underwent physical examination on their knee and standing full-limb radiography for anthropometric measurements. Linear, kinetic, and kinematic parameters were compared using a three-dimensional, 12-camera motion capture system. Gait parameters were evaluated and determinants for sex difference were evaluated with multiple regression analysis. Females had a higher peak knee adduction moment (KAM) during gait (p = 0.004). Females had relatively wider pelvis and narrower step width (both p < 0.001). However, coronal knee alignment was not significantly different between the sexes. Multiple regression analysis revealed that coronal alignment (b = 0.014, p < 0.001), step width (b = -0.010, p = 0.011), and pelvic width/height ratio (b = 1.703, p = 0.046) were significant determinants of peak KAM. Because coronal alignment was not different between the sexes, narrow step width and high pelvic width/height ratio of female were the main contributors to higher peak KAM in females. Sex differences in knee biomechanics were present in the geriatric population. Increased mechanical loading on the female knee, which was associated with narrow step width and wide pelvis, may play an important role in future development and progression of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1283-1289, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Biosynthesis of extracellular and intracellular gold nanoparticles by Aspergillus fumigatus and A. flavus.

PubMed

Gupta, Saurabh; Bector, Shruti

2013-05-01

Green chemistry is a boon for the development of safe, stable and ecofriendly nanostructures using biological tools. The present study was carried out to explore the potential of selected fungal strains for biosynthesis of intra- and extracellular gold nanostructures. Out of the seven cultures, two fungal strains (SBS-3 and SBS-7) were selected on the basis of development of dark pink colour in cell free supernatant and fungal beads, respectively indicative of extra- and intracellular gold nanoparticles production. Both biomass associated and cell free gold nanoparticles were characterized using X-ray diffractogram (XRD) analysis and transmission electron microscopy (TEM). XRD analysis confirmed crystalline, face-centered cubic lattice of metallic gold nanoparticles along with average crystallite size. A marginal difference in average crystallite size of extracellular (17.76 nm) and intracellular (26 and 22 nm) Au-nanostructures was observed using Scherrer equation. In TEM, a variety of shapes (triangles, spherical, hexagonal) were observed in both extra- and intracellular nanoparticles. 18S rRNA gene sequence analysis by multiple sequence alignment (BLAST) indicated 99 % homology of SBS-3 to Aspergillus fumigatus with 99 % alignment coverage and 98 % homology of SBS-7 to Aspergillus flavus with 98 % alignment coverage respectively. Native-PAGE and activity staining further confirmed enzyme linked synthesis of gold nanoparticles.

System and method for 2D workpiece alignment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, William T.; Carlson, Charles T.; Smith, Scott A.

2015-07-14

A carrier capable of holding one or more workpieces is disclosed. The carrier includes movable projections located along the sides of each cell in the carrier. This carrier, in conjunction with a separate alignment apparatus, aligns each workpiece within its respective cell against several alignment pins, using a multiple step alignment process to guarantee proper positioning of the workpiece in the cell. First, the workpieces are moved toward one side of the cell. Once the workpieces have been aligned against this side, the workpieces are then moved toward an adjacent orthogonal side such that the workpieces are aligned to twomore » sides of the cell. Once aligned, the workpiece is held in place by the projections located along each side of each cell. In addition, the alignment pins are also used to align the associated mask, thereby guaranteeing that the mask is properly aligned to the workpiece.« less

Phylogenetic Characterization of Transport Protein Superfamilies: Superiority of SuperfamilyTree Programs over Those Based on Multiple Alignments

PubMed Central

Chen, Jonathan S.; Reddy, Vamsee; Chen, Joshua H.; Shlykov, Maksim A.; Zheng, Wei Hao; Cho, Jaehoon; Yen, Ming Ren; Saier, Milton H.

2012-01-01

Transport proteins function in the translocation of ions, solutes and macromolecules across cellular and organellar membranes. These integral membrane proteins fall into >600 families as tabulated in the Transporter Classification Database (www.tcdb.org). Recent studies, some of which are reported here, define distant phylogenetic relationships between families with the creation of superfamilies. Several of these are analyzed using a novel set of programs designed to allow reliable prediction of phylogenetic trees when sequence divergence is too great to allow the use of multiple alignments. These new programs, called SuperfamilyTree1 and 2 (SFT1 and 2), allow display of protein and family relationships, respectively, based on thousands of comparative BLAST scores rather than multiple alignments. Superfamilies analyzed include: (1) Aerolysins, (2) RTX Toxins, (3) Defensins, (4) Ion Transporters, (5) Bile/Arsenite/Riboflavin Transporters, (6) Cation: Proton Antiporters, and (7) the Glucose/Fructose/Lactose superfamily within the prokaryotic phosphoenol pyruvate-dependent Phosphotransferase System. In addition to defining the phylogenetic relationships of the proteins and families within these seven superfamilies, evidence is provided showing that the SFT programs outperform programs that are based on multiple alignments whenever sequence divergence of superfamily members is extensive. The SFT programs should be applicable to virtually any superfamily of proteins or nucleic acids. PMID:22286036

Phylogenetic relationships within the cyst-forming nematodes (Nematoda, Heteroderidae) based on analysis of sequences from the ITS regions of ribosomal DNA.

PubMed

Subbotin, S A; Vierstraete, A; De Ley, P; Rowe, J; Waeyenberge, L; Moens, M; Vanfleteren, J R

2001-10-01

The ITS1, ITS2, and 5.8S gene sequences of nuclear ribosomal DNA from 40 taxa of the family Heteroderidae (including the genera Afenestrata, Cactodera, Heterodera, Globodera, Punctodera, Meloidodera, Cryphodera, and Thecavermiculatus) were sequenced and analyzed. The ITS regions displayed high levels of sequence divergence within Heteroderinae and compared to outgroup taxa. Unlike recent findings in root knot nematodes, ITS sequence polymorphism does not appear to complicate phylogenetic analysis of cyst nematodes. Phylogenetic analyses with maximum-parsimony, minimum-evolution, and maximum-likelihood methods were performed with a range of computer alignments, including elision and culled alignments. All multiple alignments and phylogenetic methods yielded similar basic structure for phylogenetic relationships of Heteroderidae. The cyst-forming nematodes are represented by six main clades corresponding to morphological characters and host specialization, with certain clades assuming different positions depending on alignment procedure and/or method of phylogenetic inference. Hypotheses of monophyly of Punctoderinae and Heteroderinae are, respectively, strongly and moderately supported by the ITS data across most alignments. Close relationships were revealed between the Avenae and the Sacchari groups and between the Humuli group and the species H. salixophila within Heteroderinae. The Goettingiana group occupies a basal position within this subfamily. The validity of the genera Afenestrata and Bidera was tested and is discussed based on molecular data. We conclude that ITS sequence data are appropriate for studies of relationships within the different species groups and less so for recovery of more ancient speciations within Heteroderidae. Copyright 2001 Academic Press.

SWPhylo - A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees.

PubMed

Yu, Xiaoyu; Reva, Oleg N

2018-01-01

Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA.

SWPhylo – A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees

PubMed Central

Yu, Xiaoyu; Reva, Oleg N

2018-01-01

Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA. PMID:29511354

Automatic variance analysis of multistage care pathways.

PubMed

Li, Xiang; Liu, Haifeng; Zhang, Shilei; Mei, Jing; Xie, Guotong; Yu, Yiqin; Li, Jing; Lakshmanan, Geetika T

2014-01-01

A care pathway (CP) is a standardized process that consists of multiple care stages, clinical activities and their relations, aimed at ensuring and enhancing the quality of care. However, actual care may deviate from the planned CP, and analysis of these deviations can help clinicians refine the CP and reduce medical errors. In this paper, we propose a CP variance analysis method to automatically identify the deviations between actual patient traces in electronic medical records (EMR) and a multistage CP. As the care stage information is usually unavailable in EMR, we first align every trace with the CP using a hidden Markov model. From the aligned traces, we report three types of deviations for every care stage: additional activities, absent activities and violated constraints, which are identified by using the techniques of temporal logic and binomial tests. The method has been applied to a CP for the management of congestive heart failure and real world EMR, providing meaningful evidence for the further improvement of care quality.

Dcode.org anthology of comparative genomic tools.

PubMed

Loots, Gabriela G; Ovcharenko, Ivan

2005-07-01

Comparative genomics provides the means to demarcate functional regions in anonymous DNA sequences. The successful application of this method to identifying novel genes is currently shifting to deciphering the non-coding encryption of gene regulation across genomes. To facilitate the practical application of comparative sequence analysis to genetics and genomics, we have developed several analytical and visualization tools for the analysis of arbitrary sequences and whole genomes. These tools include two alignment tools, zPicture and Mulan; a phylogenetic shadowing tool, eShadow for identifying lineage- and species-specific functional elements; two evolutionary conserved transcription factor analysis tools, rVista and multiTF; a tool for extracting cis-regulatory modules governing the expression of co-regulated genes, Creme 2.0; and a dynamic portal to multiple vertebrate and invertebrate genome alignments, the ECR Browser. Here, we briefly describe each one of these tools and provide specific examples on their practical applications. All the tools are publicly available at the http://www.dcode.org/ website.

Modeling, Simulation, and Analysis of a Decoy State Enabled Quantum Key Distribution System

DTIC Science & Technology

2015-03-26

through the fiber , we assume Alice and Bob have correct basis alignment and timing control for reference frame correction and precise photon detection...optical components ( laser , polarization modulator, electronic variable optical attenuator, fixed optical attenuator, fiber channel, beamsplitter...generated by the laser in the CPG propagate through multiple optical components, each with a unique propagation delay before reaching the OPM. Timing

Effect of Capacitive and Resistive electric transfer on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise.

PubMed

Yokota, Yuki; Sonoda, Takuya; Tashiro, Yuto; Suzuki, Yusuke; Kajiwara, Yu; Zeidan, Hala; Nakayama, Yasuaki; Kawagoe, Mirei; Shimoura, Kanako; Tatsumi, Masataka; Nakai, Kengo; Nishida, Yuichi; Bito, Tsubasa; Yoshimi, Soyoka; Aoyama, Tomoki

2018-05-01

[Purpose] This study aimed to clarify the effects of Capacitive and Resistive electric transfer (CRet) on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise. [Subjects and Methods] Twenty-two healthy males were assigned into either the CRet (n=11) or control (n=11) group. Fatiguing exercise and CRet intervention were applied at the quadriceps muscle of the participants' dominant legs. The Ely test, pelvic tilt, lumbar lordosis, and superficial temperature were measured before and after exercise and for 30 minutes after intervention. Statistical analysis was performed using one-way analysis of variance, with Tukey's post-hoc multiple comparison test to clarify within-group changes and Student's t-test to clarify between-group differences. [Results] The Ely test and pelvic tilt were significantly different in both groups after exercise, but there was no difference in the CRet group after intervention. Superficial temperature significantly increased in the CRet group for 30 minutes after intervention, in contrast to after the exercise and intervention in the control group. There was no significant between-group difference at any timepoint, except in superficial temperature. [Conclusion] CRet could effectively improve muscle flexibility and lumbopelvic alignment after fatiguing exercise.

Effect of Capacitive and Resistive electric transfer on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise

PubMed Central

Yokota, Yuki; Sonoda, Takuya; Tashiro, Yuto; Suzuki, Yusuke; Kajiwara, Yu; Zeidan, Hala; Nakayama, Yasuaki; Kawagoe, Mirei; Shimoura, Kanako; Tatsumi, Masataka; Nakai, Kengo; Nishida, Yuichi; Bito, Tsubasa; Yoshimi, Soyoka; Aoyama, Tomoki

2018-01-01

[Purpose] This study aimed to clarify the effects of Capacitive and Resistive electric transfer (CRet) on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise. [Subjects and Methods] Twenty-two healthy males were assigned into either the CRet (n=11) or control (n=11) group. Fatiguing exercise and CRet intervention were applied at the quadriceps muscle of the participants’ dominant legs. The Ely test, pelvic tilt, lumbar lordosis, and superficial temperature were measured before and after exercise and for 30 minutes after intervention. Statistical analysis was performed using one-way analysis of variance, with Tukey’s post-hoc multiple comparison test to clarify within-group changes and Student’s t-test to clarify between-group differences. [Results] The Ely test and pelvic tilt were significantly different in both groups after exercise, but there was no difference in the CRet group after intervention. Superficial temperature significantly increased in the CRet group for 30 minutes after intervention, in contrast to after the exercise and intervention in the control group. There was no significant between-group difference at any timepoint, except in superficial temperature. [Conclusion] CRet could effectively improve muscle flexibility and lumbopelvic alignment after fatiguing exercise. PMID:29765189

Cellular and Nuclear Alignment Analysis for Determining Epithelial Cell Chirality

PubMed Central

Raymond, Michael J.; Ray, Poulomi; Kaur, Gurleen; Singh, Ajay V.; Wan, Leo Q.

2015-01-01

Left-right (LR) asymmetry is a biologically conserved property in living organisms that can be observed in the asymmetrical arrangement of organs and tissues and in tissue morphogenesis, such as the directional looping of the gastrointestinal tract and heart. The expression of LR asymmetry in embryonic tissues can be appreciated in biased cell alignment. Previously an in vitro chirality assay was reported by patterning multiple cells on microscale defined geometries and quantified the cell phenotype–dependent LR asymmetry, or cell chirality. However, morphology and chirality of individual cells on micropatterned surfaces has not been well characterized. Here, a Python-based algorithm was developed to identify and quantify immunofluorescence stained individual epithelial cells on multicellular patterns. This approach not only produces results similar to the image intensity gradient-based method reported previously, but also can capture properties of single cells such as area and aspect ratio. We also found that cell nuclei exhibited biased alignment. Around 35% cells were misaligned and were typically smaller and less elongated. This new imaging analysis approach is an effective tool for measuring single cell chirality inside multicellular structures and can potentially help unveil biophysical mechanisms underlying cellular chiral bias both in vitro and in vivo. PMID:26294010

Alignment method for solar collector arrays

DOEpatents

Driver, Jr., Richard B

2012-10-23

The present invention is directed to an improved method for establishing camera fixture location for aligning mirrors on a solar collector array (SCA) comprising multiple mirror modules. The method aligns the mirrors on a module by comparing the location of the receiver image in photographs with the predicted theoretical receiver image location. To accurately align an entire SCA, a common reference is used for all of the individual module images within the SCA. The improved method can use relative pixel location information in digital photographs along with alignment fixture inclinometer data to calculate relative locations of the fixture between modules. The absolute locations are determined by minimizing alignment asymmetry for the SCA. The method inherently aligns all of the mirrors in an SCA to the receiver, even with receiver position and module-to-module alignment errors.

Isolation and identification of multidrug-resistant Staphylococcus haemolyticus from a laboratory-breeding mouse.

PubMed

Huang, Fengying; Meng, Qiuping; Tan, Guanghong; Huang, Yonghao; Wang, Hua; Mei, Wenli; Dai, Haofu

2011-06-01

To analysis and identify a bacterium strain isolated from laboratory breeding mouse far away from a hospital. Phenotype of the isolate was investigated by conventional microbiological methods, including Gram-staining, colony morphology, tests for haemolysis, catalase, coagulase, and antimicrobial susceptibility test. The mecA and 16S rRNA genes were amplified by the polymerase chain reaction (PCR) and sequenced. The base sequence of the PCR product was compared with known 16S rRNA gene sequences in the GenBank database by phylogenetic analysis and multiple sequence alignment. The isolate in this study was a gram positive, coagulase negative, and catalase positive coccus. The isolate was resistant to oxacillin, methicillin, penicillin, ampicillin, cefazolin, ciprofloxacin erythromycin, et al. PCR results indicated that the isolate was mecA gene positive and its 16S rRNA was 1 465 bp. Phylogenetic analysis of the resultant 16S rRNA indicated the isolate belonged to genus Saphylococcus, and multiple sequence alignment showed that the isolate was Saphylococcus haemolyticus with only one base difference from the corresponding 16S rRNA deposited in the GenBank. 16S rRNA gene sequencing is a suitable technique for non-specialist researchers. Laboratory animals are possible sources of lethal pathogens, and researchers must adapt protective measures when they manipulate animals. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Is It Working? Distractor Analysis Results from the Test Of Astronomy STandards (TOAST) Assessment Instrument

NASA Astrophysics Data System (ADS)

Slater, Stephanie

2009-05-01

The Test Of Astronomy STandards (TOAST) assessment instrument is a multiple-choice survey tightly aligned to the consensus learning goals stated by the American Astronomical Society - Chair's Conference on ASTRO 101, the American Association of the Advancement of Science's Project 2061 Benchmarks, and the National Research Council's National Science Education Standards. Researchers from the Cognition in Astronomy, Physics and Earth sciences Research (CAPER) Team at the University of Wyoming's Science and Math Teaching Center (UWYO SMTC) have been conducting a question-by-question distractor analysis procedure to determine the sensitivity and effectiveness of each item. In brief, the frequency each possible answer choice, known as a foil or distractor on a multiple-choice test, is determined and compared to the existing literature on the teaching and learning of astronomy. In addition to having statistical difficulty and discrimination values, a well functioning assessment item will show students selecting distractors in the relative proportions to how we expect them to respond based on known misconceptions and reasoning difficulties. In all cases, our distractor analysis suggests that all items are functioning as expected. These results add weight to the validity of the Test Of Astronomy STandards (TOAST) assessment instrument, which is designed to help instructors and researchers measure the impact of course-length duration instructional strategies for undergraduate science survey courses with learning goals tightly aligned to the consensus goals of the astronomy education community.

TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics

PubMed Central

Röst, Hannes L.; Liu, Yansheng; D’Agostino, Giuseppe; Zanella, Matteo; Navarro, Pedro; Rosenberger, George; Collins, Ben C.; Gillet, Ludovic; Testa, Giuseppe; Malmström, Lars; Aebersold, Ruedi

2016-01-01

Large scale, quantitative proteomic studies have become essential for the analysis of clinical cohorts, large perturbation experiments and systems biology studies. While next-generation mass spectrometric techniques such as SWATH-MS have substantially increased throughput and reproducibility, ensuring consistent quantification of thousands of peptide analytes across multiple LC-MS/MS runs remains a challenging and laborious manual process. To produce highly consistent and quantitatively accurate proteomics data matrices in an automated fashion, we have developed the TRIC software which utilizes fragment ion data to perform cross-run alignment, consistent peak-picking and quantification for high throughput targeted proteomics. TRIC uses a graph-based alignment strategy based on non-linear retention time correction to integrate peak elution information from all LC-MS/MS runs acquired in a study. When compared to state-of-the-art SWATH-MS data analysis, the algorithm was able to reduce the identification error by more than 3-fold at constant recall, while correcting for highly non-linear chromatographic effects. On a pulsed-SILAC experiment performed on human induced pluripotent stem (iPS) cells, TRIC was able to automatically align and quantify thousands of light and heavy isotopic peak groups and substantially increased the quantitative completeness and biological information in the data, providing insights into protein dynamics of iPS cells. Overall, this study demonstrates the importance of consistent quantification in highly challenging experimental setups, and proposes an algorithm to automate this task, constituting the last missing piece in a pipeline for automated analysis of massively parallel targeted proteomics datasets. PMID:27479329

Phylogeny Reconstruction with Alignment-Free Method That Corrects for Horizontal Gene Transfer.

PubMed

Bromberg, Raquel; Grishin, Nick V; Otwinowski, Zbyszek

2016-06-01

Advances in sequencing have generated a large number of complete genomes. Traditionally, phylogenetic analysis relies on alignments of orthologs, but defining orthologs and separating them from paralogs is a complex task that may not always be suited to the large datasets of the future. An alternative to traditional, alignment-based approaches are whole-genome, alignment-free methods. These methods are scalable and require minimal manual intervention. We developed SlopeTree, a new alignment-free method that estimates evolutionary distances by measuring the decay of exact substring matches as a function of match length. SlopeTree corrects for horizontal gene transfer, for composition variation and low complexity sequences, and for branch-length nonlinearity caused by multiple mutations at the same site. We tested SlopeTree on 495 bacteria, 73 archaea, and 72 strains of Escherichia coli and Shigella. We compared our trees to the NCBI taxonomy, to trees based on concatenated alignments, and to trees produced by other alignment-free methods. The results were consistent with current knowledge about prokaryotic evolution. We assessed differences in tree topology over different methods and settings and found that the majority of bacteria and archaea have a core set of proteins that evolves by descent. In trees built from complete genomes rather than sets of core genes, we observed some grouping by phenotype rather than phylogeny, for instance with a cluster of sulfur-reducing thermophilic bacteria coming together irrespective of their phyla. The source-code for SlopeTree is available at: http://prodata.swmed.edu/download/pub/slopetree_v1/slopetree.tar.gz.

Phylogeny Reconstruction with Alignment-Free Method That Corrects for Horizontal Gene Transfer

PubMed Central

Grishin, Nick V.; Otwinowski, Zbyszek

2016-01-01

Advances in sequencing have generated a large number of complete genomes. Traditionally, phylogenetic analysis relies on alignments of orthologs, but defining orthologs and separating them from paralogs is a complex task that may not always be suited to the large datasets of the future. An alternative to traditional, alignment-based approaches are whole-genome, alignment-free methods. These methods are scalable and require minimal manual intervention. We developed SlopeTree, a new alignment-free method that estimates evolutionary distances by measuring the decay of exact substring matches as a function of match length. SlopeTree corrects for horizontal gene transfer, for composition variation and low complexity sequences, and for branch-length nonlinearity caused by multiple mutations at the same site. We tested SlopeTree on 495 bacteria, 73 archaea, and 72 strains of Escherichia coli and Shigella. We compared our trees to the NCBI taxonomy, to trees based on concatenated alignments, and to trees produced by other alignment-free methods. The results were consistent with current knowledge about prokaryotic evolution. We assessed differences in tree topology over different methods and settings and found that the majority of bacteria and archaea have a core set of proteins that evolves by descent. In trees built from complete genomes rather than sets of core genes, we observed some grouping by phenotype rather than phylogeny, for instance with a cluster of sulfur-reducing thermophilic bacteria coming together irrespective of their phyla. The source-code for SlopeTree is available at: http://prodata.swmed.edu/download/pub/slopetree_v1/slopetree.tar.gz. PMID:27336403

Combined process automation for large-scale EEG analysis.

PubMed

Sfondouris, John L; Quebedeaux, Tabitha M; Holdgraf, Chris; Musto, Alberto E

2012-01-01

Epileptogenesis is a dynamic process producing increased seizure susceptibility. Electroencephalography (EEG) data provides information critical in understanding the evolution of epileptiform changes throughout epileptic foci. We designed an algorithm to facilitate efficient large-scale EEG analysis via linked automation of multiple data processing steps. Using EEG recordings obtained from electrical stimulation studies, the following steps of EEG analysis were automated: (1) alignment and isolation of pre- and post-stimulation intervals, (2) generation of user-defined band frequency waveforms, (3) spike-sorting, (4) quantification of spike and burst data and (5) power spectral density analysis. This algorithm allows for quicker, more efficient EEG analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

ExoLocator--an online view into genetic makeup of vertebrate proteins.

PubMed

Khoo, Aik Aun; Ogrizek-Tomas, Mario; Bulovic, Ana; Korpar, Matija; Gürler, Ece; Slijepcevic, Ivan; Šikic, Mile; Mihalek, Ivana

2014-01-01

ExoLocator (http://exolocator.eopsf.org) collects in a single place information needed for comparative analysis of protein-coding exons from vertebrate species. The main source of data--the genomic sequences, and the existing exon and homology annotation--is the ENSEMBL database of completed vertebrate genomes. To these, ExoLocator adds the search for ostensibly missing exons in orthologous protein pairs across species, using an extensive computational pipeline to narrow down the search region for the candidate exons and find a suitable template in the other species, as well as state-of-the-art implementations of pairwise alignment algorithms. The resulting complements of exons are organized in a way currently unique to ExoLocator: multiple sequence alignments, both on the nucleotide and on the peptide levels, clearly indicating the exon boundaries. The alignments can be inspected in the web-embedded viewer, downloaded or used on the spot to produce an estimate of conservation within orthologous sets, or functional divergence across paralogues.

HAL: a hierarchical format for storing and analyzing multiple genome alignments.

PubMed

Hickey, Glenn; Paten, Benedict; Earl, Dent; Zerbino, Daniel; Haussler, David

2013-05-15

Large multiple genome alignments and inferred ancestral genomes are ideal resources for comparative studies of molecular evolution, and advances in sequencing and computing technology are making them increasingly obtainable. These structures can provide a rich understanding of the genetic relationships between all subsets of species they contain. Current formats for storing genomic alignments, such as XMFA and MAF, are all indexed or ordered using a single reference genome, however, which limits the information that can be queried with respect to other species and clades. This loss of information grows with the number of species under comparison, as well as their phylogenetic distance. We present HAL, a compressed, graph-based hierarchical alignment format for storing multiple genome alignments and ancestral reconstructions. HAL graphs are indexed on all genomes they contain. Furthermore, they are organized phylogenetically, which allows for modular and parallel access to arbitrary subclades without fragmentation because of rearrangements that have occurred in other lineages. HAL graphs can be created or read with a comprehensive C++ API. A set of tools is also provided to perform basic operations, such as importing and exporting data, identifying mutations and coordinate mapping (liftover). All documentation and source code for the HAL API and tools are freely available at http://github.com/glennhickey/hal. hickey@soe.ucsc.edu or haussler@soe.ucsc.edu Supplementary data are available at Bioinformatics online.

Resolving the multiple sequence alignment problem using biogeography-based optimization with multiple populations.

PubMed

Zemali, El-Amine; Boukra, Abdelmadjid

2015-08-01

The multiple sequence alignment (MSA) is one of the most challenging problems in bioinformatics, it involves discovering similarity between a set of protein or DNA sequences. This paper introduces a new method for the MSA problem called biogeography-based optimization with multiple populations (BBOMP). It is based on a recent metaheuristic inspired from the mathematics of biogeography named biogeography-based optimization (BBO). To improve the exploration ability of BBO, we have introduced a new concept allowing better exploration of the search space. It consists of manipulating multiple populations having each one its own parameters. These parameters are used to build up progressive alignments allowing more diversity. At each iteration, the best found solution is injected in each population. Moreover, to improve solution quality, six operators are defined. These operators are selected with a dynamic probability which changes according to the operators efficiency. In order to test proposed approach performance, we have considered a set of datasets from Balibase 2.0 and compared it with many recent algorithms such as GAPAM, MSA-GA, QEAMSA and RBT-GA. The results show that the proposed approach achieves better average score than the previously cited methods.

MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis.

PubMed

Kumar, Sudhir; Stecher, Glen; Peterson, Daniel; Tamura, Koichiro

2012-10-15

There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis. http://www.megasoftware.net/.

Characterization and functional analyses of a novel chicken CD8a variant X1 (CD8a1)

USDA-ARS?s Scientific Manuscript database

We provide the first description of cloning, as well as structural and functional analysis of a novel variant in the chicken CD8alpha family, termed the CD8-alpha X1 (CD8alpha1) gene. Multiple alignment of CD8alpha1 with known CD8alpha and beta sequences of other species revealed relatively low con...

Derivation of Multiple Covarying Material and Process Parameters Using Physics-Based Modeling of X-ray Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khaira, Gurdaman; Doxastakis, Manolis; Bowen, Alec

There is considerable interest in developing multimodal characterization frameworks capable of probing critical properties of complex materials by relying on distinct, complementary methods or tools. Any such framework should maximize the amount of information that is extracted from any given experiment and should be sufficiently powerful and efficient to enable on-the-fly analysis of multiple measurements in a self-consistent manner. Such a framework is demonstrated in this work in the context of self-assembling polymeric materials, where theory and simulations provide the language to seamlessly mesh experimental data from two different scattering measurements. Specifically, the samples considered here consist of diblock copolymersmore » (BCP) that are self-assembled on chemically nanopatterned surfaces. The copolymers microphase separate into ordered lamellae with characteristic dimensions on the scale of tens of nanometers that are perfectly aligned by the substrate over macroscopic areas. These aligned lamellar samples provide ideal standards with which to develop the formalism introduced in this work and, more generally, the concept of high-information-content, multimodal experimentation. The outcomes of the proposed analysis are then compared to images generated by 3D scanning electron microscopy tomography, serving to validate the merit of the framework and ideas proposed here.« less

Dinucleotide controlled null models for comparative RNA gene prediction.

PubMed

Gesell, Tanja; Washietl, Stefan

2008-05-27

Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak et al. [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. 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. 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. SISSIz is available as open source C code that can be compiled for every major platform and downloaded here: http://sourceforge.net/projects/sissiz.

MC64-ClustalWP2: A Highly-Parallel Hybrid Strategy to Align Multiple Sequences in Many-Core Architectures

PubMed Central

Díaz, David; Esteban, Francisco J.; Hernández, Pilar; Caballero, Juan Antonio; Guevara, Antonio

2014-01-01

We have developed the MC64-ClustalWP2 as a new implementation of the Clustal W algorithm, integrating a novel parallelization strategy and significantly increasing the performance when aligning long sequences in architectures with many cores. It must be stressed that in such a process, the detailed analysis of both the software and hardware features and peculiarities is of paramount importance to reveal key points to exploit and optimize the full potential of parallelism in many-core CPU systems. The new parallelization approach has focused into the most time-consuming stages of this algorithm. In particular, the so-called progressive alignment has drastically improved the performance, due to a fine-grained approach where the forward and backward loops were unrolled and parallelized. Another key approach has been the implementation of the new algorithm in a hybrid-computing system, integrating both an Intel Xeon multi-core CPU and a Tilera Tile64 many-core card. A comparison with other Clustal W implementations reveals the high-performance of the new algorithm and strategy in many-core CPU architectures, in a scenario where the sequences to align are relatively long (more than 10 kb) and, hence, a many-core GPU hardware cannot be used. Thus, the MC64-ClustalWP2 runs multiple alignments more than 18x than the original Clustal W algorithm, and more than 7x than the best x86 parallel implementation to date, being publicly available through a web service. Besides, these developments have been deployed in cost-effective personal computers and should be useful for life-science researchers, including the identification of identities and differences for mutation/polymorphism analyses, biodiversity and evolutionary studies and for the development of molecular markers for paternity testing, germplasm management and protection, to assist breeding, illegal traffic control, fraud prevention and for the protection of the intellectual property (identification/traceability), including the protected designation of origin, among other applications. PMID:24710354

Robust prediction of consensus secondary structures using averaged base pairing probability matrices.

PubMed

Kiryu, Hisanori; Kin, Taishin; Asai, Kiyoshi

2007-02-15

Recent transcriptomic studies have revealed the existence of a considerable number of non-protein-coding RNA transcripts in higher eukaryotic cells. To investigate the functional roles of these transcripts, it is of great interest to find conserved secondary structures from multiple alignments on a genomic scale. Since multiple alignments are often created using alignment programs that neglect the special conservation patterns of RNA secondary structures for computational efficiency, alignment failures can cause potential risks of overlooking conserved stem structures. We investigated the dependence of the accuracy of secondary structure prediction on the quality of alignments. We compared three algorithms that maximize the expected accuracy of secondary structures as well as other frequently used algorithms. We found that one of our algorithms, called McCaskill-MEA, was more robust against alignment failures than others. The McCaskill-MEA method first computes the base pairing probability matrices for all the sequences in the alignment and then obtains the base pairing probability matrix of the alignment by averaging over these matrices. The consensus secondary structure is predicted from this matrix such that the expected accuracy of the prediction is maximized. We show that the McCaskill-MEA method performs better than other methods, particularly when the alignment quality is low and when the alignment consists of many sequences. Our model has a parameter that controls the sensitivity and specificity of predictions. We discussed the uses of that parameter for multi-step screening procedures to search for conserved secondary structures and for assigning confidence values to the predicted base pairs. The C++ source code that implements the McCaskill-MEA algorithm and the test dataset used in this paper are available at http://www.ncrna.org/papers/McCaskillMEA/. Supplementary data are available at Bioinformatics online.

HAlign-II: efficient ultra-large multiple sequence alignment and phylogenetic tree reconstruction with distributed and parallel computing.

PubMed

Wan, Shixiang; Zou, Quan

2017-01-01

Multiple sequence alignment (MSA) plays a key role in biological sequence analyses, especially in phylogenetic tree construction. Extreme increase in next-generation sequencing results in shortage of efficient ultra-large biological sequence alignment approaches for coping with different sequence types. Distributed and parallel computing represents a crucial technique for accelerating ultra-large (e.g. files more than 1 GB) sequence analyses. Based on HAlign and Spark distributed computing system, we implement a highly cost-efficient and time-efficient HAlign-II tool to address ultra-large multiple biological sequence alignment and phylogenetic tree construction. The experiments in the DNA and protein large scale data sets, which are more than 1GB files, showed that HAlign II could save time and space. It outperformed the current software tools. HAlign-II can efficiently carry out MSA and construct phylogenetic trees with ultra-large numbers of biological sequences. HAlign-II shows extremely high memory efficiency and scales well with increases in computing resource. THAlign-II provides a user-friendly web server based on our distributed computing infrastructure. HAlign-II with open-source codes and datasets was established at http://lab.malab.cn/soft/halign.

QuickProbs 2: Towards rapid construction of high-quality alignments of large protein families

PubMed Central

Gudyś, Adam; Deorowicz, Sebastian

2017-01-01

The ever-increasing size of sequence databases caused by the development of high throughput sequencing, poses to multiple alignment algorithms one of the greatest challenges yet. As we show, well-established techniques employed for increasing alignment quality, i.e., refinement and consistency, are ineffective when large protein families are investigated. We present QuickProbs 2, an algorithm for multiple sequence alignment. Based on probabilistic models, equipped with novel column-oriented refinement and selective consistency, it offers outstanding accuracy. When analysing hundreds of sequences, Quick-Probs 2 is noticeably better than ClustalΩ and MAFFT, the previous leaders for processing numerous protein families. In the case of smaller sets, for which consistency-based methods are the best performing, QuickProbs 2 is also superior to the competitors. Due to low computational requirements of selective consistency and utilization of massively parallel architectures, presented algorithm has similar execution times to ClustalΩ, and is orders of magnitude faster than full consistency approaches, like MSAProbs or PicXAA. All these make QuickProbs 2 an excellent tool for aligning families ranging from few, to hundreds of proteins. PMID:28139687

Photovoltaic module and interlocked stack of photovoltaic modules

DOEpatents

Wares, Brian S.

2014-09-02

One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

CHROMA: consensus-based colouring of multiple alignments for publication.

PubMed

Goodstadt, L; Ponting, C P

2001-09-01

CHROMA annotates multiple protein sequence alignments by consensus to produce formatted and coloured text suitable for incorporation into other documents for publication. The package is designed to be flexible and reliable, and has a simple-to-use graphical user interface running under Microsoft Windows. Both the executables and source code for CHROMA running under Windows and Linux (portable command-line only) are freely available at http://www.lg.ndirect.co.uk/chroma. Software enquiries should be directed to CHROMA@lg.ndirect.co.uk.

ChromA: signal-based retention time alignment for chromatography-mass spectrometry data.

PubMed

Hoffmann, Nils; Stoye, Jens

2009-08-15

We describe ChromA, a web-based alignment tool for chromatography-mass spectrometry data from the metabolomics and proteomics domains. Users can supply their data in open and standardized file formats for retention time alignment using dynamic time warping with different configurable local distance and similarity functions. Additionally, user-defined anchors can be used to constrain and speedup the alignment. A neighborhood around each anchor can be added to increase the flexibility of the constrained alignment. ChromA offers different visualizations of the alignment for easier qualitative interpretation and comparison of the data. For the multiple alignment of more than two data files, the center-star approximation is applied to select a reference among input files to align to. ChromA is available at http://bibiserv.techfak.uni-bielefeld.de/chroma. Executables and source code under the L-GPL v3 license are provided for download at the same location.

Spatio-temporal alignment of multiple sensors

NASA Astrophysics Data System (ADS)

Zhang, Tinghua; Ni, Guoqiang; Fan, Guihua; Sun, Huayan; Yang, Biao

2018-01-01

Aiming to achieve the spatio-temporal alignment of multi sensor on the same platform for space target observation, a joint spatio-temporal alignment method is proposed. To calibrate the parameters and measure the attitude of cameras, an astronomical calibration method is proposed based on star chart simulation and collinear invariant features of quadrilateral diagonal between the observed star chart. In order to satisfy a temporal correspondence and spatial alignment similarity simultaneously, the method based on the astronomical calibration and attitude measurement in this paper formulates the video alignment to fold the spatial and temporal alignment into a joint alignment framework. The advantage of this method is reinforced by exploiting the similarities and prior knowledge of velocity vector field between adjacent frames, which is calculated by the SIFT Flow algorithm. The proposed method provides the highest spatio-temporal alignment accuracy compared to the state-of-the-art methods on sequences recorded from multi sensor at different times.

Non-lethal sampling for the detection of Myxobolus cerebralis in asymptomatic rainbow trout

USGS Publications Warehouse

Schill, Bane; Waldrop, Thomas; Densmore, Christine; Blazer, Vicki

1999-01-01

We have described in previous reports (Schill et al., 1998) the development of a polymerase chain reaction (PCR) amplification of 18S ribosomal RNA for the detection of Myxozoan parasites. Oligonucleotide primers were developed by multiple alignment of Myxozoan sequence information and analysis by a custom-written computer program (PRIM). Candidate pairs of primer sequences were then analyzed for specificity by BLAST (Basic Local Alignment Search Tool). From these, a set of promising primers (MYXFWD and MYXREV) was chosen for further testing. These were chosen because they should direct detection of a number of Myxozoan species (Table 1). PCR using MXYFWD and MYXREV proved to be robust and relatively free of artifact products. Further, we were able to routinely detect Myxobolus cerebralis in fish tissues (Figure 1).

The Saccharomyces Genome Database Variant Viewer

PubMed Central

Sheppard, Travis K.; Hitz, Benjamin C.; Engel, Stacia R.; Song, Giltae; Balakrishnan, Rama; Binkley, Gail; Costanzo, Maria C.; Dalusag, Kyla S.; Demeter, Janos; Hellerstedt, Sage T.; Karra, Kalpana; Nash, Robert S.; Paskov, Kelley M.; Skrzypek, Marek S.; Weng, Shuai; Wong, Edith D.; Cherry, J. Michael

2016-01-01

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer. PMID:26578556

Micro-scale and meso-scale architectural cues cooperate and compete to direct aligned tissue formation

PubMed Central

Gilchrist, Christopher L.; Ruch, David S.; Little, Dianne; Guilak, Farshid

2014-01-01

Tissue and biomaterial microenvironments provide architectural cues that direct important cell behaviors including cell shape, alignment, migration, and resulting tissue formation. These architectural features may be presented to cells across multiple length scales, from nanometers to millimeters in size. In this study, we examined how architectural cues at two distinctly different length scales, “micro-scale” cues on the order of ~1–2 μm, and “meso-scale” cues several orders of magnitude larger (>100 μm), interact to direct aligned neo-tissue formation. Utilizing a micro-photopatterning (μPP) model system to precisely arrange cell-adhesive patterns, we examined the effects of substrate architecture at these length scales on human mesenchymal stem cell (hMSC) organization, gene expression, and fibrillar collagen deposition. Both micro- and meso-scale architectures directed cell alignment and resulting tissue organization, and when combined, meso cues could enhance or compete against micro-scale cues. As meso boundary aspect ratios were increased, meso-scale cues overrode micro-scale cues and controlled tissue alignment, with a characteristic critical width (~500 μm) similar to boundary dimensions that exist in vivo in highly aligned tissues. Meso-scale cues acted via both lateral confinement (in a cell-density-dependent manner) and by permitting end-to-end cell arrangements that yielded greater fibrillar collagen deposition. Despite large differences in fibrillar collagen content and organization between μPP architectural conditions, these changes did not correspond with changes in gene expression of key matrix or tendon-related genes. These findings highlight the complex interplay between geometric cues at multiple length scales and may have implications for tissue engineering strategies, where scaffold designs that incorporate cues at multiple length scales could improve neo-tissue organization and resulting functional outcomes. PMID:25263687

MRI-based analysis of patellofemoral cartilage contact, thickness, and alignment in extension, and during moderate and deep flexion.

PubMed

Freedman, Benjamin R; Sheehan, Frances T; Lerner, Amy L

2015-10-01

Several factors are believed to contribute to patellofemoral joint function throughout knee flexion including patellofemoral (PF) kinematics, contact, and bone morphology. However, data evaluating the PF joint in this highly flexed state have been limited. Therefore, the purpose of this study was to evaluate patellofemoral contact and alignment in low (0°), moderate (60°), and deep (140°) knee flexion, and then correlate these parameters to each other, as well as to femoral morphology. Sagittal magnetic resonance images were acquired on 14 healthy female adult knees (RSRB approved) using a 1.5 T scanner with the knee in full extension, mid-flexion, and deep flexion. The patellofemoral cartilage contact area, lateral contact displacement (LCD), cartilage thickness, and lateral patellar displacement (LPD) throughout flexion were defined. Intra- and inter-rater repeatability measures were determined. Correlations between patellofemoral contact parameters, alignment, and sulcus morphology were calculated. Measurement repeatability ICCs ranged from 0.94 to 0.99. Patellofemoral cartilage contact area and thickness, LCD, and LPD were statistically different throughout all levels of flexion (p<0.001). The cartilage contact area was correlated to LPD, cartilage thickness, sulcus angle, and epicondylar width (r=0.47-0.72, p<0.05). This study provides a comprehensive analysis of the patellofemoral joint throughout its range of motion. This study agrees with past studies that investigated patellofemoral measures at a single flexion angle, and provides new insights into the relationship between patellofemoral contact and alignment at multiple flexion angles. The study provides a detailed analysis of the patellofemoral joint in vivo, and demonstrates the feasibility of using standard clinical magnetic resonance imaging scanners to image the knee joint in deep flexion. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved measurements of RNA structure conservation with generalized centroid estimators.

PubMed

Okada, Yohei; Saito, Yutaka; Sato, Kengo; Sakakibara, Yasubumi

2011-01-01

Identification of non-protein-coding RNAs (ncRNAs) in genomes is a crucial task for not only molecular cell biology but also bioinformatics. Secondary structures of ncRNAs are employed as a key feature of ncRNA analysis since biological functions of ncRNAs are deeply related to their secondary structures. Although the minimum free energy (MFE) structure of an RNA sequence is regarded as the most stable structure, MFE alone could not be an appropriate measure for identifying ncRNAs since the free energy is heavily biased by the nucleotide composition. Therefore, instead of MFE itself, several alternative measures for identifying ncRNAs have been proposed such as the structure conservation index (SCI) and the base pair distance (BPD), both of which employ MFE structures. However, these measurements are unfortunately not suitable for identifying ncRNAs in some cases including the genome-wide search and incur high false discovery rate. In this study, we propose improved measurements based on SCI and BPD, applying generalized centroid estimators to incorporate the robustness against low quality multiple alignments. Our experiments show that our proposed methods achieve higher accuracy than the original SCI and BPD for not only human-curated structural alignments but also low quality alignments produced by CLUSTAL W. Furthermore, the centroid-based SCI on CLUSTAL W alignments is more accurate than or comparable with that of the original SCI on structural alignments generated with RAF, a high quality structural aligner, for which twofold expensive computational time is required on average. We conclude that our methods are more suitable for genome-wide alignments which are of low quality from the point of view on secondary structures than the original SCI and BPD.

Alignment in the transverse plane, but not sagittal or coronal plane, affects the risk of recurrent patella dislocation.

PubMed

Takagi, Shigeru; Sato, Takashi; Watanabe, Satoshi; Tanifuji, Osamu; Mochizuki, Tomoharu; Omori, Go; Endo, Naoto

2017-11-17

Abnormalities of lower extremity alignment (LEA) in recurrent patella dislocation (RPD) have been studied mostly by two-dimensional (2D) procedures leaving three-dimensional (3D) factors unknown. This study aimed to three-dimensionally examine risk factors for RPD in lower extremity alignment under the weight-bearing conditions. The alignment of 21 limbs in 15 RPD subjects was compared to the alignment of 24 limbs of 12 healthy young control subjects by an our previously reported 2D-3D image-matching technique. The sagittal, coronal, and transverse alignment in full extension as well as the torsional position of the femur (anteversion) and tibia (tibial torsion) under weight-bearing standing conditions were assessed by our previously reported 3D technique. The correlations between lower extremity alignment and RPD were assessed using multiple logistic regression analysis. The difference of lower extremity alignment in RPD between under the weight-bearing conditions and under the non-weight-bearing conditions was assessed. In the sagittal and coronal planes, there was no relationship (statistically or by clinically important difference) between lower extremity alignment angle and RPD. However, in the transverse plane, increased external tibial rotation [odds ratio (OR) 1.819; 95% confidence interval (CI) 1.282-2.581], increased femoral anteversion (OR 1.183; 95% CI 1.029-1.360), and increased external tibial torsion (OR 0.880; 95% CI 0.782-0.991) were all correlated with RPD. The tibia was more rotated relative to femur at the knee joint in the RPD group under the weight-bearing conditions compared to under the non-weight-bearing conditions (p < 0.05). This study showed that during weight-bearing, alignment parameters in the transverse plane related to the risk of RPD, while in the sagittal and coronal plane alignment parameters did not correlate with RPD. The clinical importance of this study is that the 3D measurements more directly, precisely, and sensitively detect rotational parameters associated with RPD and hence predict risk of RPD. III.

Parallel multipoint recording of aligned and cultured neurons on corresponding Micro Channel Array toward on-chip cell analysis.

PubMed

Tonomura, W; Moriguchi, H; Jimbo, Y; Konishi, S

2008-01-01

This paper describes an advanced Micro Channel Array (MCA) so as to record neuronal network at multiple points simultaneously. Developed MCA is designed for neuronal network analysis which has been studied by co-authors using MEA (Micro Electrode Arrays) system. The MCA employs the principle of the extracellular recording. Presented MCA has the following advantages. First of all, the electrodes integrated around individual micro channels are electrically isolated for parallel multipoint recording. Sucking and clamping of cells through micro channels is expected to improve the cellular selectivity and S/N ratio. In this study, hippocampal neurons were cultured on the developed MCA. As a result, the spontaneous and evoked spike potential could be recorded by sucking and clamping the cells at multiple points. Herein, we describe the successful experimental results together with the design and fabrication of the advanced MCA toward on-chip analysis of neuronal network.

BEAUTY: an enhanced BLAST-based search tool that integrates multiple biological information resources into sequence similarity search results.

PubMed

Worley, K C; Wiese, B A; Smith, R F

1995-09-01

BEAUTY (BLAST enhanced alignment utility) is an enhanced version of the NCBI's BLAST data base search tool that facilitates identification of the functions of matched sequences. We have created new data bases of conserved regions and functional domains for protein sequences in NCBI's Entrez data base, and BEAUTY allows this information to be incorporated directly into BLAST search results. A Conserved Regions Data Base, containing the locations of conserved regions within Entrez protein sequences, was constructed by (1) clustering the entire data base into families, (2) aligning each family using our PIMA multiple sequence alignment program, and (3) scanning the multiple alignments to locate the conserved regions within each aligned sequence. A separate Annotated Domains Data Base was constructed by extracting the locations of all annotated domains and sites from sequences represented in the Entrez, PROSITE, BLOCKS, and PRINTS data bases. BEAUTY performs a BLAST search of those Entrez sequences with conserved regions and/or annotated domains. BEAUTY then uses the information from the Conserved Regions and Annotated Domains data bases to generate, for each matched sequence, a schematic display that allows one to directly compare the relative locations of (1) the conserved regions, (2) annotated domains and sites, and (3) the locally aligned regions matched in the BLAST search. In addition, BEAUTY search results include World-Wide Web hypertext links to a number of external data bases that provide a variety of additional types of information on the function of matched sequences. This convenient integration of protein families, conserved regions, annotated domains, alignment displays, and World-Wide Web resources greatly enhances the biological informativeness of sequence similarity searches. BEAUTY searches can be performed remotely on our system using the "BCM Search Launcher" World-Wide Web pages (URL is < http:/ /gc.bcm.tmc.edu:8088/ search-launcher/launcher.html > ).

Processing and population genetic analysis of multigenic datasets with ProSeq3 software.

PubMed

Filatov, Dmitry A

2009-12-01

The current tendency in molecular population genetics is to use increasing numbers of genes in the analysis. Here I describe a program for handling and population genetic analysis of DNA polymorphism data collected from multiple genes. The program includes a sequence/alignment editor and an internal relational database that simplify the preparation and manipulation of multigenic DNA polymorphism datasets. The most commonly used DNA polymorphism analyses are implemented in ProSeq3, facilitating population genetic analysis of large multigenic datasets. Extensive input/output options make ProSeq3 a convenient hub for sequence data processing and analysis. The program is available free of charge from http://dps.plants.ox.ac.uk/sequencing/proseq.htm.

Determining the Cost-Savings Threshold and Alignment Accuracy of Patient-Specific Instrumentation in Total Ankle Replacements.

PubMed

Hamid, Kamran S; Matson, Andrew P; Nwachukwu, Benedict U; Scott, Daniel J; Mather, Richard C; DeOrio, James K

2017-01-01

Traditional intraoperative referencing for total ankle replacements (TARs) involves multiple steps and fluoroscopic guidance to determine mechanical alignment. Recent adoption of patient-specific instrumentation (PSI) allows for referencing to be determined preoperatively, resulting in less steps and potentially decreased operative time. We hypothesized that usage of PSI would result in decreased operating room time that would offset the additional cost of PSI compared with standard referencing (SR). In addition, we aimed to compare postoperative radiographic alignment between PSI and SR. Between August 2014 and September 2015, 87 patients undergoing TAR were enrolled in a prospectively collected TAR database. Patients were divided into cohorts based on PSI vs SR, and operative times were reviewed. Radiographic alignment parameters were retrospectively measured at 6 weeks postoperatively. Time-driven activity-based costing (TDABC) was used to derive direct costs. Cost vs operative time-savings were examined via 2-way sensitivity analysis to determine cost-saving thresholds for PSI applicable to a range of institution types. Cost-saving thresholds defined the price of PSI below which PSI would be cost-saving. A total of 35 PSI and 52 SR cases were evaluated with no significant differences identified in patient characteristics. Operative time from incision to completion of casting in cases without adjunct procedures was 127 minutes with PSI and 161 minutes with SR ( P < .05). PSI demonstrated similar postoperative accuracy to SR in coronal tibial-plafond alignment (1.1 vs 0.3 degrees varus, P = .06), tibial-plafond alignment (0.3 ± 2.1 vs 1.1 ± 2.1 degrees varus, P = .06), and tibial component sagittal alignment (0.7 vs 0.9 degrees plantarflexion, P = .14). The TDABC method estimated a PSI cost-savings threshold range at our institution of $863 below which PSI pricing would provide net cost-savings. Two-way sensitivity analysis generated a globally applicable cost-savings threshold model based on institution-specific costs and surgeon-specific time-savings. This study demonstrated equivalent postoperative TAR alignment with PSI and SR referencing systems but with a significant decrease in operative time with PSI. Based on TDABC and associated sensitivity analysis, a cost-savings threshold of $863 was identified for PSI pricing at our institution below which PSI was less costly than SR. Similar internal cost accounting may benefit health care systems for identifying cost drivers and obtaining leverage during price negotiations. Level III, therapeutic study.

Sequence alignment visualization in HTML5 without Java.

PubMed

Gille, Christoph; Birgit, Weyand; Gille, Andreas

2014-01-01

Java has been extensively used for the visualization of biological data in the web. However, the Java runtime environment is an additional layer of software with an own set of technical problems and security risks. HTML in its new version 5 provides features that for some tasks may render Java unnecessary. Alignment-To-HTML is the first HTML-based interactive visualization for annotated multiple sequence alignments. The server side script interpreter can perform all tasks like (i) sequence retrieval, (ii) alignment computation, (iii) rendering, (iv) identification of a homologous structural models and (v) communication with BioDAS-servers. The rendered alignment can be included in web pages and is displayed in all browsers on all platforms including touch screen tablets. The functionality of the user interface is similar to legacy Java applets and includes color schemes, highlighting of conserved and variable alignment positions, row reordering by drag and drop, interlinked 3D visualization and sequence groups. Novel features are (i) support for multiple overlapping residue annotations, such as chemical modifications, single nucleotide polymorphisms and mutations, (ii) mechanisms to quickly hide residue annotations, (iii) export to MS-Word and (iv) sequence icons. Alignment-To-HTML, the first interactive alignment visualization that runs in web browsers without additional software, confirms that to some extend HTML5 is already sufficient to display complex biological data. The low speed at which programs are executed in browsers is still the main obstacle. Nevertheless, we envision an increased use of HTML and JavaScript for interactive biological software. Under GPL at: http://www.bioinformatics.org/strap/toHTML/.

eHive: an artificial intelligence workflow system for genomic analysis.

PubMed

Severin, Jessica; Beal, Kathryn; Vilella, Albert J; Fitzgerald, Stephen; Schuster, Michael; Gordon, Leo; Ureta-Vidal, Abel; Flicek, Paul; Herrero, Javier

2010-05-11

The Ensembl project produces updates to its comparative genomics resources with each of its several releases per year. During each release cycle approximately two weeks are allocated to generate all the genomic alignments and the protein homology predictions. The number of calculations required for this task grows approximately quadratically with the number of species. We currently support 50 species in Ensembl and we expect the number to continue to grow in the future. We present eHive, a new fault tolerant distributed processing system initially designed to support comparative genomic analysis, based on blackboard systems, network distributed autonomous agents, dataflow graphs and block-branch diagrams. In the eHive system a MySQL database serves as the central blackboard and the autonomous agent, a Perl script, queries the system and runs jobs as required. The system allows us to define dataflow and branching rules to suit all our production pipelines. We describe the implementation of three pipelines: (1) pairwise whole genome alignments, (2) multiple whole genome alignments and (3) gene trees with protein homology inference. Finally, we show the efficiency of the system in real case scenarios. eHive allows us to produce computationally demanding results in a reliable and efficient way with minimal supervision and high throughput. Further documentation is available at: http://www.ensembl.org/info/docs/eHive/.

CCD Camera Lens Interface for Real-Time Theodolite Alignment

NASA Technical Reports Server (NTRS)

Wake, Shane; Scott, V. Stanley, III

2012-01-01

Theodolites are a common instrument in the testing, alignment, and building of various systems ranging from a single optical component to an entire instrument. They provide a precise way to measure horizontal and vertical angles. They can be used to align multiple objects in a desired way at specific angles. They can also be used to reference a specific location or orientation of an object that has moved. Some systems may require a small margin of error in position of components. A theodolite can assist with accurately measuring and/or minimizing that error. The technology is an adapter for a CCD camera with lens to attach to a Leica Wild T3000 Theodolite eyepiece that enables viewing on a connected monitor, and thus can be utilized with multiple theodolites simultaneously. This technology removes a substantial part of human error by relying on the CCD camera and monitors. It also allows image recording of the alignment, and therefore provides a quantitative means to measure such error.

PSI/TM-Coffee: a web server for fast and accurate multiple sequence alignments of regular and transmembrane proteins using homology extension on reduced databases.

PubMed

Floden, Evan W; Tommaso, Paolo D; Chatzou, Maria; Magis, Cedrik; Notredame, Cedric; Chang, Jia-Ming

2016-07-08

The PSI/TM-Coffee web server performs multiple sequence alignment (MSA) of proteins by combining homology extension with a consistency based alignment approach. Homology extension is performed with Position Specific Iterative (PSI) BLAST searches against a choice of redundant and non-redundant databases. The main novelty of this server is to allow databases of reduced complexity to rapidly perform homology extension. This server also gives the possibility to use transmembrane proteins (TMPs) reference databases to allow even faster homology extension on this important category of proteins. Aside from an MSA, the server also outputs topological prediction of TMPs using the HMMTOP algorithm. Previous benchmarking of the method has shown this approach outperforms the most accurate alignment methods such as MSAProbs, Kalign, PROMALS, MAFFT, ProbCons and PRALINE™. The web server is available at http://tcoffee.crg.cat/tmcoffee. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Multi-Harmony: detecting functional specificity from sequence alignment

PubMed Central

Brandt, Bernd W.; Feenstra, K. Anton; Heringa, Jaap

2010-01-01

Many protein families contain sub-families with functional specialization, such as binding different ligands or being involved in different protein–protein interactions. A small number of amino acids generally determine functional specificity. The identification of these residues can aid the understanding of protein function and help finding targets for experimental analysis. Here, we present multi-Harmony, an interactive web sever for detecting sub-type-specific sites in proteins starting from a multiple sequence alignment. Combining our Sequence Harmony (SH) and multi-Relief (mR) methods in one web server allows simultaneous analysis and comparison of specificity residues; furthermore, both methods have been significantly improved and extended. SH has been extended to cope with more than two sub-groups. mR has been changed from a sampling implementation to a deterministic one, making it more consistent and user friendly. For both methods Z-scores are reported. The multi-Harmony web server produces a dynamic output page, which includes interactive connections to the Jalview and Jmol applets, thereby allowing interactive analysis of the results. Multi-Harmony is available at http://www.ibi.vu.nl/ programs/shmrwww. PMID:20525785

Population-based structural variation discovery with Hydra-Multi.

PubMed

Lindberg, Michael R; Hall, Ira M; Quinlan, Aaron R

2015-04-15

Current strategies for SNP and INDEL discovery incorporate sequence alignments from multiple individuals to maximize sensitivity and specificity. It is widely accepted that this approach also improves structural variant (SV) detection. However, multisample SV analysis has been stymied by the fundamental difficulties of SV calling, e.g. library insert size variability, SV alignment signal integration and detecting long-range genomic rearrangements involving disjoint loci. Extant tools suffer from poor scalability, which limits the number of genomes that can be co-analyzed and complicates analysis workflows. We have developed an approach that enables multisample SV analysis in hundreds to thousands of human genomes using commodity hardware. Here, we describe Hydra-Multi and measure its accuracy, speed and scalability using publicly available datasets provided by The 1000 Genomes Project and by The Cancer Genome Atlas (TCGA). Hydra-Multi is written in C++ and is freely available at https://github.com/arq5x/Hydra. aaronquinlan@gmail.com or ihall@genome.wustl.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

DCODE.ORG Anthology of Comparative Genomic Tools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loots, G G; Ovcharenko, I

2005-01-11

Comparative genomics provides the means to demarcate functional regions in anonymous DNA sequences. The successful application of this method to identifying novel genes is currently shifting to deciphering the noncoding encryption of gene regulation across genomes. To facilitate the use of comparative genomics to practical applications in genetics and genomics we have developed several analytical and visualization tools for the analysis of arbitrary sequences and whole genomes. These tools include two alignment tools: zPicture and Mulan; a phylogenetic shadowing tool: eShadow for identifying lineage- and species-specific functional elements; two evolutionary conserved transcription factor analysis tools: rVista and multiTF; a toolmore » for extracting cis-regulatory modules governing the expression of co-regulated genes, CREME; and a dynamic portal to multiple vertebrate and invertebrate genome alignments, the ECR Browser. Here we briefly describe each one of these tools and provide specific examples on their practical applications. All the tools are publicly available at the http://www.dcode.org/ web site.« less

Desorption Kinetics of Ar, Kr, Xe, N2, O2, CO, Methane, Ethane, and Propane from Graphene and Amorphous Solid Water Surfaces.

PubMed

Smith, R Scott; May, R Alan; Kay, Bruce D

2016-03-03

The desorption kinetics for Ar, Kr, Xe, N2, O2, CO, methane, ethane, and propane from graphene-covered Pt(111) and amorphous solid water (ASW) surfaces are investigated using temperature-programmed desorption (TPD). The TPD spectra for all of the adsorbates from graphene have well-resolved first, second, third, and multilayer desorption peaks. The alignment of the leading edges is consistent the zero-order desorption for all of the adsorbates. An Arrhenius analysis is used to obtain desorption energies and prefactors for desorption from graphene for all of the adsorbates. In contrast, the leading desorption edges for the adsorbates from ASW do not align (for coverages < 2 ML). The nonalignment of TPD leading edges suggests that there are multiple desorption binding sites on the ASW surface. Inversion analysis is used to obtain the coverage dependent desorption energies and prefactors for desorption from ASW for all of the adsorbates.

Unified Alignment of Protein-Protein Interaction Networks.

PubMed

Malod-Dognin, Noël; Ban, Kristina; Pržulj, Nataša

2017-04-19

Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.

GeneSilico protein structure prediction meta-server.

PubMed

Kurowski, Michal A; Bujnicki, Janusz M

2003-07-01

Rigorous assessments of protein structure prediction have demonstrated that fold recognition methods can identify remote similarities between proteins when standard sequence search methods fail. It has been shown that the accuracy of predictions is improved when refined multiple sequence alignments are used instead of single sequences and if different methods are combined to generate a consensus model. There are several meta-servers available that integrate protein structure predictions performed by various methods, but they do not allow for submission of user-defined multiple sequence alignments and they seldom offer confidentiality of the results. We developed a novel WWW gateway for protein structure prediction, which combines the useful features of other meta-servers available, but with much greater flexibility of the input. The user may submit an amino acid sequence or a multiple sequence alignment to a set of methods for primary, secondary and tertiary structure prediction. Fold-recognition results (target-template alignments) are converted into full-atom 3D models and the quality of these models is uniformly assessed. A consensus between different FR methods is also inferred. The results are conveniently presented on-line on a single web page over a secure, password-protected connection. The GeneSilico protein structure prediction meta-server is freely available for academic users at http://genesilico.pl/meta.

GeneSilico protein structure prediction meta-server

PubMed Central

Kurowski, Michal A.; Bujnicki, Janusz M.

2003-01-01

Rigorous assessments of protein structure prediction have demonstrated that fold recognition methods can identify remote similarities between proteins when standard sequence search methods fail. It has been shown that the accuracy of predictions is improved when refined multiple sequence alignments are used instead of single sequences and if different methods are combined to generate a consensus model. There are several meta-servers available that integrate protein structure predictions performed by various methods, but they do not allow for submission of user-defined multiple sequence alignments and they seldom offer confidentiality of the results. We developed a novel WWW gateway for protein structure prediction, which combines the useful features of other meta-servers available, but with much greater flexibility of the input. The user may submit an amino acid sequence or a multiple sequence alignment to a set of methods for primary, secondary and tertiary structure prediction. Fold-recognition results (target-template alignments) are converted into full-atom 3D models and the quality of these models is uniformly assessed. A consensus between different FR methods is also inferred. The results are conveniently presented on-line on a single web page over a secure, password-protected connection. The GeneSilico protein structure prediction meta-server is freely available for academic users at http://genesilico.pl/meta. PMID:12824313

Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

PubMed Central

Wang, Xu; Le, Anh-Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

2016-01-01

We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. A simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method. PMID:27025410

Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

NASA Astrophysics Data System (ADS)

Wang, Xu; Le, Anh-Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

2016-03-01

We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. A simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method.

Centroid stabilization in alignment of FOA corner cube: designing of a matched filter

NASA Astrophysics Data System (ADS)

Awwal, Abdul; Wilhelmsen, Karl; Roberts, Randy; Leach, Richard; Miller Kamm, Victoria; Ngo, Tony; Lowe-Webb, Roger

2015-02-01

The current automation of image-based alignment of NIF high energy laser beams is providing the capability of executing multiple target shots per day. An important aspect of performing multiple shots in a day is to reduce additional time spent aligning specific beams due to perturbations in those beam images. One such alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retro-reflecting corner cubes to represent the beam center. The FOA houses the frequency conversion crystals for third harmonic generation as the beams enters the target chamber. Beam-to-beam variations and systematic beam changes over time in the FOA corner-cube images can lead to a reduction in accuracy as well as increased convergence durations for the template based centroid detector. This work presents a systematic approach of maintaining FOA corner cube centroid templates so that stable position estimation is applied thereby leading to fast convergence of alignment control loops. In the matched filtering approach, a template is designed based on most recent images taken in the last 60 days. The results show that new filter reduces the divergence of the position estimation of FOA images.

GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters.

PubMed

Sela, Itamar; Ashkenazy, Haim; Katoh, Kazutaka; Pupko, Tal

2015-07-01

Inference of multiple sequence alignments (MSAs) is a critical part of phylogenetic and comparative genomics studies. However, from the same set of sequences different MSAs are often inferred, depending on the methodologies used and the assumed parameters. Much effort has recently been devoted to improving the ability to identify unreliable alignment regions. Detecting such unreliable regions was previously shown to be important for downstream analyses relying on MSAs, such as the detection of positive selection. Here we developed GUIDANCE2, a new integrative methodology that accounts for: (i) uncertainty in the process of indel formation, (ii) uncertainty in the assumed guide tree and (iii) co-optimal solutions in the pairwise alignments, used as building blocks in progressive alignment algorithms. We compared GUIDANCE2 with seven methodologies to detect unreliable MSA regions using extensive simulations and empirical benchmarks. We show that GUIDANCE2 outperforms all previously developed methodologies. Furthermore, GUIDANCE2 also provides a set of alternative MSAs which can be useful for downstream analyses. The novel algorithm is implemented as a web-server, available at: http://guidance.tau.ac.il. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analysis of Knee Joint Line Obliquity after High Tibial Osteotomy.

PubMed

Oh, Kwang-Jun; Ko, Young Bong; Bae, Ji Hoon; Yoon, Suk Tae; Kim, Jae Gyoon

2016-11-01

The aim of this study was to evaluate which lower extremity alignment (knee and ankle joint) parameters affect knee joint line obliquity (KJLO) in the coronal plane after open wedge high tibial osteotomy (OWHTO). Overall, 69 knees of patients that underwent OWHTO were evaluated using radiographs obtained preoperatively and from 6 weeks to 3 months postoperatively. We measured multiple parameters of knee and ankle joint alignment (hip-knee-ankle angle [HKA], joint line height [JLH], posterior tibial slope [PS], femoral condyle-tibial plateau angle [FCTP], medial proximal tibial angle [MPTA], mechanical lateral distal femoral angle [mLDFA], KJLO, talar tilt angle [TTA], ankle joint obliquity [AJO], and the lateral distal tibial ground surface angle [LDTGA]; preoperative [-pre], postoperative [-post], and the difference between -pre and -post values [-Δ]). We categorized patients into two groups according to the KJLO-post value (the normal group [within ± 4 degrees, 56 knees] and the abnormal group [greater than ± 4 degrees, 13 knees]), and compared their -pre parameters. Multiple logistic regression analysis was used to examine the contribution of the -pre parameters to abnormal KJLO-post. The mean HKA-Δ (-9.4 ± 4.7 degrees) was larger than the mean KJLO-Δ (-2.1 ± 3.2 degrees). The knee joint alignment parameters (the HKA-pre, FCTP-pre) differed significantly between the two groups ( p  < 0.05). In addition, the HKA-pre (odds ratio [OR] = 1.27, p  = 0.006) and FCTP-pre (OR = 2.13, p  = 0.006) were significant predictors of abnormal KJLO-post. However, -pre ankle joint parameters (TTA, AJO, and LDTGA) did not differ significantly between the two groups and were not significantly associated with the abnormal KJLO-post. The -pre knee joint alignment and knee joint convergence angle evaluated by HKA-pre and FCTP-pre angle, respectively, were significant predictors of abnormal KJLO after OWHTO. However, -pre ankle joint parameters were not significantly associated with abnormal KJLO after OWHTO. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

MultiSeq: unifying sequence and structure data for evolutionary analysis

PubMed Central

Roberts, Elijah; Eargle, John; Wright, Dan; Luthey-Schulten, Zaida

2006-01-01

Background Since the publication of the first draft of the human genome in 2000, bioinformatic data have been accumulating at an overwhelming pace. Currently, more than 3 million sequences and 35 thousand structures of proteins and nucleic acids are available in public databases. Finding correlations in and between these data to answer critical research questions is extremely challenging. This problem needs to be approached from several directions: information science to organize and search the data; information visualization to assist in recognizing correlations; mathematics to formulate statistical inferences; and biology to analyze chemical and physical properties in terms of sequence and structure changes. Results Here we present MultiSeq, a unified bioinformatics analysis environment that allows one to organize, display, align and analyze both sequence and structure data for proteins and nucleic acids. While special emphasis is placed on analyzing the data within the framework of evolutionary biology, the environment is also flexible enough to accommodate other usage patterns. The evolutionary approach is supported by the use of predefined metadata, adherence to standard ontological mappings, and the ability for the user to adjust these classifications using an electronic notebook. MultiSeq contains a new algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of a homologous group of distantly related proteins. The method, based on the multidimensional QR factorization of multiple sequence and structure alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. Conclusion MultiSeq is a major extension of the Multiple Alignment tool that is provided as part of VMD, a structural visualization program for analyzing molecular dynamics simulations. Both are freely distributed by the NIH Resource for Macromolecular Modeling and Bioinformatics and MultiSeq is included with VMD starting with version 1.8.5. The MultiSeq website has details on how to download and use the software: PMID:16914055

StructAlign, a Program for Alignment of Structures of DNA-Protein Complexes.

PubMed

Popov, Ya V; Galitsyna, A A; Alexeevski, A V; Karyagina, A S; Spirin, S A

2015-11-01

Comparative analysis of structures of complexes of homologous proteins with DNA is important in the analysis of DNA-protein recognition. Alignment is a necessary stage of the analysis. An alignment is a matching of amino acid residues and nucleotides of one complex to residues and nucleotides of the other. Currently, there are no programs available for aligning structures of DNA-protein complexes. We present the program StructAlign, which should fill this gap. The program inputs a pair of complexes of DNA double helix with proteins and outputs an alignment of DNA chains corresponding to the best spatial fit of the protein chains.

Multicolor microcontact printing of proteins on nanoporous surface for patterned immunoassay

NASA Astrophysics Data System (ADS)

Ng, Elaine; Gopal, Ashwini; Hoshino, Kazunori; Zhang, Xiaojing

2011-07-01

The large scale patterning of therapeutic proteins is a key to the efficient design, characterization, and production of biologics for cost effective, high throughput, and point-of-care detection and analysis system. We demonstrate an efficient method for protein deposition and adsorption on nanoporous silica substrates in specific patterns using a method called "micro-contact printing". Multiple color-tagged proteins can be printed through sequential application of such micro-patterning technique. Two groups of experiments were performed. In the first group, the protein stamp was aligned precisely with the printing sites, where the stamp was applied multiple times. Optimal conditions were identified for protein transfer and adsorption using the pore size of 4 nm and thickness of 30 nm porous silica thin film. In the second group, we demonstrate the patterning of two-color rabbit immunoglobin labeled with fluorescein isothiocyanate and tetramethyl rhodamine iso-thiocyanate on porous silica substrates that have a pore size 4 nm, porosity 57% and thickness of the porous layer 30 nm. A pair of protein stamps, with corresponding alignment markings and coupled patterns, were aligned and used to produce a two-colored stamp pattern of proteins on porous silica. Different colored proteins can be applied to exemplify the diverse protein composition within a sample. This method of multicolor microcontact printing can be used to perform a fluorescence-based patterned enzyme-linked immunosorbent assay to detect the presence of various proteins within a sample.

Dynamo Catalogue: Geometrical tools and data management for particle picking in subtomogram averaging of cryo-electron tomograms.

PubMed

Castaño-Díez, Daniel; Kudryashev, Mikhail; Stahlberg, Henning

2017-02-01

Cryo electron tomography allows macromolecular complexes within vitrified, intact, thin cells or sections thereof to be visualized, and structural analysis to be performed in situ by averaging over multiple copies of the same molecules. Image processing for subtomogram averaging is specific and cumbersome, due to the large amount of data and its three dimensional nature and anisotropic resolution. Here, we streamline data processing for subtomogram averaging by introducing an archiving system, Dynamo Catalogue. This system manages tomographic data from multiple tomograms and allows visual feedback during all processing steps, including particle picking, extraction, alignment and classification. The file structure of a processing project file structure includes logfiles of performed operations, and can be backed up and shared between users. Command line commands, database queries and a set of GUIs give the user versatile control over the process. Here, we introduce a set of geometric tools that streamline particle picking from simple (filaments, spheres, tubes, vesicles) and complex geometries (arbitrary 2D surfaces, rare instances on proteins with geometric restrictions, and 2D and 3D crystals). Advanced functionality, such as manual alignment and subboxing, is useful when initial templates are generated for alignment and for project customization. Dynamo Catalogue is part of the open source package Dynamo and includes tools to ensure format compatibility with the subtomogram averaging functionalities of other packages, such as Jsubtomo, PyTom, PEET, EMAN2, XMIPP and Relion. Copyright © 2016. Published by Elsevier Inc.

How do we deal with multiple goals for care within an individual patient trajectory? A document content analysis of health service research papers on goals for care

PubMed Central

Berntsen, G K R; Gammon, D; Steinsbekk, A; Salamonsen, A; Foss, N; Ruland, C; Fønnebø, V

2015-01-01

Objectives Patients with complex long-term needs experience multiple parallel care processes, which may have conflicting or competing goals, within their individual patient trajectory (iPT). The alignment of multiple goals is often implicit or non-existent, and has received little attention in the literature. Research questions: (1) What goals for care relevant for the iPT can be identified from the literature? (2) What goal typology can be proposed based on goal characteristics? (3) How can professionals negotiate a consistent set of goals for the iPT? Design Document content analysis of health service research papers, on the topic of ‘goals for care’. Setting With the increasing prevalence of multimorbidity, guidance regarding the identification and alignment of goals for care across organisations and disciplines is urgently needed. Participants 70 papers that describe ‘goals for care’, ‘health’ or ‘the good healthcare process’ relevant to a general iPT, identified in a step-wise structured search of MEDLINE, Web of Science and Google Scholar. Results We developed a goal typology with four categories. Three categories are professionally defined: (1) Functional, (2) Biological/Disease and (3) Adaptive goals. The fourth category is the patient's personally defined goals. Professional and personal goals may conflict, in which case goal prioritisation by creation of a goal hierarchy can be useful. We argue that the patient has the moral and legal right to determine the goals at the top of such a goal hierarchy. Professionals can then translate personal goals into realistic professional goals such as standardised health outcomes linked to evidence-based guidelines. Thereby, when goals are aligned with one another, the iPT will be truly patient centred, while care follows professional guidelines. Conclusions Personal goals direct professional goals and define the success criteria of the iPT. However, making personal goals count requires brave and wide-sweeping attitudinal, organisational and regulatory transformation of care delivery. PMID:26656243

Multiple nodes transfer alignment for airborne missiles based on inertial sensor network

NASA Astrophysics Data System (ADS)

Si, Fan; Zhao, Yan

2017-09-01

Transfer alignment is an important initialization method for airborne missiles because the alignment accuracy largely determines the performance of the missile. However, traditional alignment methods are limited by complicated and unknown flexure angle, and cannot meet the actual requirement when wing flexure deformation occurs. To address this problem, we propose a new method that uses the relative navigation parameters between the weapons and fighter to achieve transfer alignment. First, in the relative inertial navigation algorithm, the relative attitudes and positions are constantly computed in wing flexure deformation situations. Secondly, the alignment results of each weapon are processed using a data fusion algorithm to improve the overall performance. Finally, the feasibility and performance of the proposed method were evaluated under two typical types of deformation, and the simulation results demonstrated that the new transfer alignment method is practical and has high-precision.

Multiple-reflection optical gas cell

DOEpatents

Matthews, Thomas G.

1983-01-01

A multiple-reflection optical cell for Raman or fluorescence gas analysis consists of two spherical mirrors positioned transverse to a multiple-pass laser cell in a confronting plane-parallel alignment. The two mirrors are of equal diameter but possess different radii of curvature. The spacing between the mirrors is uniform and less than half of the radius of curvature of either mirror. The mirror of greater curvature possesses a small circular portal in its center which is the effective point source for conventional F1 double lens collection optics of a monochromator-detection system. Gas to be analyzed is flowed into the cell and irradiated by a multiply-reflected composite laser beam centered between the mirrors of the cell. Raman or fluorescence radiation originating from a large volume within the cell is (1) collected via multiple reflections with the cell mirrors, (2) partially collimated and (3) directed through the cell portal in a geometric array compatible with F1 collection optics.

Detecting and accounting for multiple sources of positional variance in peak list registration analysis and spin system grouping.

PubMed

Smelter, Andrey; Rouchka, Eric C; Moseley, Hunter N B

2017-08-01

Peak lists derived from nuclear magnetic resonance (NMR) spectra are commonly used as input data for a variety of computer assisted and automated analyses. These include automated protein resonance assignment and protein structure calculation software tools. Prior to these analyses, peak lists must be aligned to each other and sets of related peaks must be grouped based on common chemical shift dimensions. Even when programs can perform peak grouping, they require the user to provide uniform match tolerances or use default values. However, peak grouping is further complicated by multiple sources of variance in peak position limiting the effectiveness of grouping methods that utilize uniform match tolerances. In addition, no method currently exists for deriving peak positional variances from single peak lists for grouping peaks into spin systems, i.e. spin system grouping within a single peak list. Therefore, we developed a complementary pair of peak list registration analysis and spin system grouping algorithms designed to overcome these limitations. We have implemented these algorithms into an approach that can identify multiple dimension-specific positional variances that exist in a single peak list and group peaks from a single peak list into spin systems. The resulting software tools generate a variety of useful statistics on both a single peak list and pairwise peak list alignment, especially for quality assessment of peak list datasets. We used a range of low and high quality experimental solution NMR and solid-state NMR peak lists to assess performance of our registration analysis and grouping algorithms. Analyses show that an algorithm using a single iteration and uniform match tolerances approach is only able to recover from 50 to 80% of the spin systems due to the presence of multiple sources of variance. Our algorithm recovers additional spin systems by reevaluating match tolerances in multiple iterations. To facilitate evaluation of the algorithms, we developed a peak list simulator within our nmrstarlib package that generates user-defined assigned peak lists from a given BMRB entry or database of entries. In addition, over 100,000 simulated peak lists with one or two sources of variance were generated to evaluate the performance and robustness of these new registration analysis and peak grouping algorithms.

MRM-DIFF: data processing strategy for differential analysis in large scale MRM-based lipidomics studies.

PubMed

Tsugawa, Hiroshi; Ohta, Erika; Izumi, Yoshihiro; Ogiwara, Atsushi; Yukihira, Daichi; Bamba, Takeshi; Fukusaki, Eiichiro; Arita, Masanori

2014-01-01

Based on theoretically calculated comprehensive lipid libraries, in lipidomics as many as 1000 multiple reaction monitoring (MRM) transitions can be monitored for each single run. On the other hand, lipid analysis from each MRM chromatogram requires tremendous manual efforts to identify and quantify lipid species. Isotopic peaks differing by up to a few atomic masses further complicate analysis. To accelerate the identification and quantification process we developed novel software, MRM-DIFF, for the differential analysis of large-scale MRM assays. It supports a correlation optimized warping (COW) algorithm to align MRM chromatograms and utilizes quality control (QC) sample datasets to automatically adjust the alignment parameters. Moreover, user-defined reference libraries that include the molecular formula, retention time, and MRM transition can be used to identify target lipids and to correct peak abundances by considering isotopic peaks. Here, we demonstrate the software pipeline and introduce key points for MRM-based lipidomics research to reduce the mis-identification and overestimation of lipid profiles. The MRM-DIFF program, example data set and the tutorials are downloadable at the "Standalone software" section of the PRIMe (Platform for RIKEN Metabolomics, http://prime.psc.riken.jp/) database website.

MRM-DIFF: data processing strategy for differential analysis in large scale MRM-based lipidomics studies

PubMed Central

Tsugawa, Hiroshi; Ohta, Erika; Izumi, Yoshihiro; Ogiwara, Atsushi; Yukihira, Daichi; Bamba, Takeshi; Fukusaki, Eiichiro; Arita, Masanori

2015-01-01

Based on theoretically calculated comprehensive lipid libraries, in lipidomics as many as 1000 multiple reaction monitoring (MRM) transitions can be monitored for each single run. On the other hand, lipid analysis from each MRM chromatogram requires tremendous manual efforts to identify and quantify lipid species. Isotopic peaks differing by up to a few atomic masses further complicate analysis. To accelerate the identification and quantification process we developed novel software, MRM-DIFF, for the differential analysis of large-scale MRM assays. It supports a correlation optimized warping (COW) algorithm to align MRM chromatograms and utilizes quality control (QC) sample datasets to automatically adjust the alignment parameters. Moreover, user-defined reference libraries that include the molecular formula, retention time, and MRM transition can be used to identify target lipids and to correct peak abundances by considering isotopic peaks. Here, we demonstrate the software pipeline and introduce key points for MRM-based lipidomics research to reduce the mis-identification and overestimation of lipid profiles. The MRM-DIFF program, example data set and the tutorials are downloadable at the “Standalone software” section of the PRIMe (Platform for RIKEN Metabolomics, http://prime.psc.riken.jp/) database website. PMID:25688256

Cloud-Coffee: implementation of a parallel consistency-based multiple alignment algorithm in the T-Coffee package and its benchmarking on the Amazon Elastic-Cloud.

PubMed

Di Tommaso, Paolo; Orobitg, Miquel; Guirado, Fernando; Cores, Fernado; Espinosa, Toni; Notredame, Cedric

2010-08-01

We present the first parallel implementation of the T-Coffee consistency-based multiple aligner. We benchmark it on the Amazon Elastic Cloud (EC2) and show that the parallelization procedure is reasonably effective. We also conclude that for a web server with moderate usage (10K hits/month) the cloud provides a cost-effective alternative to in-house deployment. T-Coffee is a freeware open source package available from http://www.tcoffee.org/homepage.html

Introduction to bioinformatics.

PubMed

Can, Tolga

2014-01-01

Bioinformatics is an interdisciplinary field mainly involving molecular biology and genetics, computer science, mathematics, and statistics. Data intensive, large-scale biological problems are addressed from a computational point of view. The most common problems are modeling biological processes at the molecular level and making inferences from collected data. A bioinformatics solution usually involves the following steps: Collect statistics from biological data. Build a computational model. Solve a computational modeling problem. Test and evaluate a computational algorithm. This chapter gives a brief introduction to bioinformatics by first providing an introduction to biological terminology and then discussing some classical bioinformatics problems organized by the types of data sources. Sequence analysis is the analysis of DNA and protein sequences for clues regarding function and includes subproblems such as identification of homologs, multiple sequence alignment, searching sequence patterns, and evolutionary analyses. Protein structures are three-dimensional data and the associated problems are structure prediction (secondary and tertiary), analysis of protein structures for clues regarding function, and structural alignment. Gene expression data is usually represented as matrices and analysis of microarray data mostly involves statistics analysis, classification, and clustering approaches. Biological networks such as gene regulatory networks, metabolic pathways, and protein-protein interaction networks are usually modeled as graphs and graph theoretic approaches are used to solve associated problems such as construction and analysis of large-scale networks.

Multiple alignment-free sequence comparison

PubMed Central

Ren, Jie; Song, Kai; Sun, Fengzhu; Deng, Minghua; Reinert, Gesine

2013-01-01

Motivation: Recently, a range of new statistics have become available for the alignment-free comparison of two sequences based on k-tuple word content. Here, we extend these statistics to the simultaneous comparison of more than two sequences. Our suite of statistics contains, first, and , extensions of statistics for pairwise comparison of the joint k-tuple content of all the sequences, and second, , and , averages of sums of pairwise comparison statistics. The two tasks we consider are, first, to identify sequences that are similar to a set of target sequences, and, second, to measure the similarity within a set of sequences. Results: Our investigation uses both simulated data as well as cis-regulatory module data where the task is to identify cis-regulatory modules with similar transcription factor binding sites. We find that although for real data, all of our statistics show a similar performance, on simulated data the Shepp-type statistics are in some instances outperformed by star-type statistics. The multiple alignment-free statistics are more sensitive to contamination in the data than the pairwise average statistics. Availability: Our implementation of the five statistics is available as R package named ‘multiAlignFree’ at be http://www-rcf.usc.edu/∼fsun/Programs/multiAlignFree/multiAlignFreemain.html. Contact: reinert@stats.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23990418

An investigation into the alignment of a South African physiotherapy curriculum and the expectations of the healthcare system.

PubMed

Ramklass, Serela S

2009-09-01

Until 1994, physiotherapy education and training were aligned with the expectations of the South African healthcare system. Subsequent to policy shifts since 1994, the professional role of physiotherapists has expanded. In the absence of guiding strategies to support this change, physiotherapy curricula have remained relatively static. The paper examines the discrepancies between physiotherapy education and training at a South African university post apartheid and the expectations of the healthcare system. Located within critical feminist research framings and employing narrative inquiry as the selected methodology, data were produced through multiple methods to obtain multiple perspectives and orientations. This multisectorial data production approach involving student physiotherapists, physiotherapy academics and practising physiotherapists included in-depth focus group interviews, individual interviews, life-history biographies and open-ended questionnaires. The data were analysed separately for each group of research participants (physiotherapy students, practitioners and academics), followed by a cross-sector analysis. The analysis illustrated current disciplinary trends and shortcomings of the physiotherapy undergraduate curriculum, whilst highlighting that which is considered valuable and progressive in physiotherapy and health care. The dominant themes that emerged included issues relating to physiotherapy theory and practice, and issues that influenced the construction of relationships in the curriculum. The significance of this study lies in the value of student and practitioner feedback to inform curriculum and professional development in the light of sociopolitical changes and healthcare expectations.

Genetic Algorithm Phase Retrieval for the Systematic Image-Based Optical Alignment Testbed

NASA Technical Reports Server (NTRS)

Rakoczy, John; Steincamp, James; Taylor, Jaime

2003-01-01

A reduced surrogate, one point crossover genetic algorithm with random rank-based selection was used successfully to estimate the multiple phases of a segmented optical system modeled on the seven-mirror Systematic Image-Based Optical Alignment testbed located at NASA's Marshall Space Flight Center.

Multiple Frequency Audio Signal Communication as a Mechanism for Neurophysiology and Video Data Synchronization

PubMed Central

Topper, Nicholas C.; Burke, S.N.; Maurer, A.P.

2014-01-01

BACKGROUND Current methods for aligning neurophysiology and video data are either prepackaged, requiring the additional purchase of a software suite, or use a blinking LED with a stationary pulse-width and frequency. These methods lack significant user interface for adaptation, are expensive, or risk a misalignment of the two data streams. NEW METHOD A cost-effective means to obtain high-precision alignment of behavioral and neurophysiological data is obtained by generating an audio-pulse embedded with two domains of information, a low-frequency binary-counting signal and a high, randomly changing frequency. This enabled the derivation of temporal information while maintaining enough entropy in the system for algorithmic alignment. RESULTS The sample to frame index constructed using the audio input correlation method described in this paper enables video and data acquisition to be aligned at a sub-frame level of precision. COMPARISONS WITH EXISTING METHOD Traditionally, a synchrony pulse is recorded on-screen via a flashing diode. The higher sampling rate of the audio input of the camcorder enables the timing of an event to be detected with greater precision. CONCLUSIONS While On-line analysis and synchronization using specialized equipment may be the ideal situation in some cases, the method presented in the current paper presents a viable, low cost alternative, and gives the flexibility to interface with custom off-line analysis tools. Moreover, the ease of constructing and implements this set-up presented in the current paper makes it applicable to a wide variety of applications that require video recording. PMID:25256648

Ensembl comparative genomics resources.

PubMed

Herrero, Javier; Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J; Searle, Stephen M J; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

2016-01-01

Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. © The Author(s) 2016. Published by Oxford University Press.

Multiple frequency audio signal communication as a mechanism for neurophysiology and video data synchronization.

PubMed

Topper, Nicholas C; Burke, Sara N; Maurer, Andrew Porter

2014-12-30

Current methods for aligning neurophysiology and video data are either prepackaged, requiring the additional purchase of a software suite, or use a blinking LED with a stationary pulse-width and frequency. These methods lack significant user interface for adaptation, are expensive, or risk a misalignment of the two data streams. A cost-effective means to obtain high-precision alignment of behavioral and neurophysiological data is obtained by generating an audio-pulse embedded with two domains of information, a low-frequency binary-counting signal and a high, randomly changing frequency. This enabled the derivation of temporal information while maintaining enough entropy in the system for algorithmic alignment. The sample to frame index constructed using the audio input correlation method described in this paper enables video and data acquisition to be aligned at a sub-frame level of precision. Traditionally, a synchrony pulse is recorded on-screen via a flashing diode. The higher sampling rate of the audio input of the camcorder enables the timing of an event to be detected with greater precision. While on-line analysis and synchronization using specialized equipment may be the ideal situation in some cases, the method presented in the current paper presents a viable, low cost alternative, and gives the flexibility to interface with custom off-line analysis tools. Moreover, the ease of constructing and implements this set-up presented in the current paper makes it applicable to a wide variety of applications that require video recording. Copyright © 2014 Elsevier B.V. All rights reserved.

Ensembl comparative genomics resources

PubMed Central

Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J.; Searle, Stephen M. J.; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

2016-01-01

Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. PMID:26896847

Alignment of gold nanorods by angular photothermal depletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Adam B.; Chow, Timothy T. Y.; Chon, James W. M., E-mail: jchon@swin.edu.au

2014-02-24

In this paper, we demonstrate that a high degree of alignment can be imposed upon randomly oriented gold nanorod films by angular photothermal depletion with linearly polarized laser irradiation. The photothermal reshaping of gold nanorods is observed to follow quadratic melting model rather than the threshold melting model, which distorts the angular and spectral hole created on 2D distribution map of nanorods to be an open crater shape. We have accounted these observations to the alignment procedures and demonstrated good agreement between experiment and simulations. The use of multiple laser depletion wavelengths allowed alignment criteria over a large range ofmore » aspect ratios, achieving 80% of the rods in the target angular range. We extend the technique to demonstrate post-alignment in a multilayer of randomly oriented gold nanorod films, with arbitrary control of alignment shown across the layers. Photothermal angular depletion alignment of gold nanorods is a simple, promising post-alignment method for creating future 3D or multilayer plasmonic nanorod based devices and structures.« less

ChromA: signal-based retention time alignment for chromatography–mass spectrometry data

PubMed Central

Hoffmann, Nils; Stoye, Jens

2009-01-01

Summary: We describe ChromA, a web-based alignment tool for chromatography–mass spectrometry data from the metabolomics and proteomics domains. Users can supply their data in open and standardized file formats for retention time alignment using dynamic time warping with different configurable local distance and similarity functions. Additionally, user-defined anchors can be used to constrain and speedup the alignment. A neighborhood around each anchor can be added to increase the flexibility of the constrained alignment. ChromA offers different visualizations of the alignment for easier qualitative interpretation and comparison of the data. For the multiple alignment of more than two data files, the center-star approximation is applied to select a reference among input files to align to. Availability: ChromA is available at http://bibiserv.techfak.uni-bielefeld.de/chroma. Executables and source code under the L-GPL v3 license are provided for download at the same location. Contact: stoye@techfak.uni-bielefeld.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19505941

The Drosophila genome nexus: a population genomic resource of 623 Drosophila melanogaster genomes, including 197 from a single ancestral range population.

PubMed

Lack, Justin B; Cardeno, Charis M; Crepeau, Marc W; Taylor, William; Corbett-Detig, Russell B; Stevens, Kristian A; Langley, Charles H; Pool, John E

2015-04-01

Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets. Copyright © 2015 by the Genetics Society of America.

A survey and evaluations of histogram-based statistics in alignment-free sequence comparison.

PubMed

Luczak, Brian B; James, Benjamin T; Girgis, Hani Z

2017-12-06

Since the dawn of the bioinformatics field, sequence alignment scores have been the main method for comparing sequences. However, alignment algorithms are quadratic, requiring long execution time. As alternatives, scientists have developed tens of alignment-free statistics for measuring the similarity between two sequences. We surveyed tens of alignment-free k-mer statistics. Additionally, we evaluated 33 statistics and multiplicative combinations between the statistics and/or their squares. These statistics are calculated on two k-mer histograms representing two sequences. Our evaluations using global alignment scores revealed that the majority of the statistics are sensitive and capable of finding similar sequences to a query sequence. Therefore, any of these statistics can filter out dissimilar sequences quickly. Further, we observed that multiplicative combinations of the statistics are highly correlated with the identity score. Furthermore, combinations involving sequence length difference or Earth Mover's distance, which takes the length difference into account, are always among the highest correlated paired statistics with identity scores. Similarly, paired statistics including length difference or Earth Mover's distance are among the best performers in finding the K-closest sequences. Interestingly, similar performance can be obtained using histograms of shorter words, resulting in reducing the memory requirement and increasing the speed remarkably. Moreover, we found that simple single statistics are sufficient for processing next-generation sequencing reads and for applications relying on local alignment. Finally, we measured the time requirement of each statistic. The survey and the evaluations will help scientists with identifying efficient alternatives to the costly alignment algorithm, saving thousands of computational hours. The source code of the benchmarking tool is available as Supplementary Materials. © The Author 2017. Published by Oxford University Press.

PrimerDesign-M: A multiple-alignment based multiple-primer design tool for walking across variable genomes

DOE PAGES

Yoon, Hyejin; Leitner, Thomas

2014-12-17

Analyses of entire viral genomes or mtDNA requires comprehensive design of many primers across their genomes. In addition, simultaneous optimization of several DNA primer design criteria may improve overall experimental efficiency and downstream bioinformatic processing. To achieve these goals, we developed PrimerDesign-M. It includes several options for multiple-primer design, allowing researchers to efficiently design walking primers that cover long DNA targets, such as entire HIV-1 genomes, and that optimizes primers simultaneously informed by genetic diversity in multiple alignments and experimental design constraints given by the user. PrimerDesign-M can also design primers that include DNA barcodes and minimize primer dimerization. PrimerDesign-Mmore » finds optimal primers for highly variable DNA targets and facilitates design flexibility by suggesting alternative designs to adapt to experimental conditions.« less

Multiple main-belt asteroid mission options for a Mariner Mark II spacecraft

NASA Astrophysics Data System (ADS)

Sauer, Carl G., Jr.; Yen, Chen-Wan L.

This paper presents the trajectory options available for a MMII spacecraft mission to asteroids and introduces systematic methods of uncovering attractive mission opportunities. The analysis presented considers multiple synchronous gravity assists of Mars and introduces a terminal resonant or phasing orbit; a concept useful for both increasing the number of asteroid rendezvous targets attainable during a launch opportunity, and also in increasing the number of potential asteroid flybys. Systematic examinations of the requirements for superior asteroidal alignments are made and a comprehensive set of asteroid rendezvous opportunities for the 1998 to 2010 period are presented. Examples of candidate missions involving one or more rendezvous and several flybys are also presented.

Multiple main-belt asteroid mission options for a Mariner Mark II spacecraft

NASA Technical Reports Server (NTRS)

Sauer, Carl G., Jr.; Yen, Chen-Wan L.

1990-01-01

This paper presents the trajectory options available for a MMII spacecraft mission to asteroids and introduces systematic methods of uncovering attractive mission opportunities. The analysis presented considers multiple synchronous gravity assists of Mars and introduces a terminal resonant or phasing orbit; a concept useful for both increasing the number of asteroid rendezvous targets attainable during a launch opportunity, and also in increasing the number of potential asteroid flybys. Systematic examinations of the requirements for superior asteroidal alignments are made and a comprehensive set of asteroid rendezvous opportunities for the 1998 to 2010 period are presented. Examples of candidate missions involving one or more rendezvous and several flybys are also presented.

JDet: interactive calculation and visualization of function-related conservation patterns in multiple sequence alignments and structures.

PubMed

Muth, Thilo; García-Martín, Juan A; Rausell, Antonio; Juan, David; Valencia, Alfonso; Pazos, Florencio

2012-02-15

We have implemented in a single package all the features required for extracting, visualizing and manipulating fully conserved positions as well as those with a family-dependent conservation pattern in multiple sequence alignments. The program allows, among other things, to run different methods for extracting these positions, combine the results and visualize them in protein 3D structures and sequence spaces. JDet is a multiplatform application written in Java. It is freely available, including the source code, at http://csbg.cnb.csic.es/JDet. The package includes two of our recently developed programs for detecting functional positions in protein alignments (Xdet and S3Det), and support for other methods can be added as plug-ins. A help file and a guided tutorial for JDet are also available.

Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

DOE PAGES

Wang, Xu; Le, Anh -Thu; Yu, Chao; ...

2016-03-30

We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. Lastly, amore » simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method.« less

BatMis: a fast algorithm for k-mismatch mapping.

PubMed

Tennakoon, Chandana; Purbojati, Rikky W; Sung, Wing-Kin

2012-08-15

Second-generation sequencing (SGS) generates millions of reads that need to be aligned to a reference genome allowing errors. Although current aligners can efficiently map reads allowing a small number of mismatches, they are not well suited for handling a large number of mismatches. The efficiency of aligners can be improved using various heuristics, but the sensitivity and accuracy of the alignments are sacrificed. In this article, we introduce Basic Alignment tool for Mismatches (BatMis)--an efficient method to align short reads to a reference allowing k mismatches. BatMis is a Burrows-Wheeler transformation based aligner that uses a seed and extend approach, and it is an exact method. Benchmark tests show that BatMis performs better than competing aligners in solving the k-mismatch problem. Furthermore, it can compete favorably even when compared with the heuristic modes of the other aligners. BatMis is a useful alternative for applications where fast k-mismatch mappings, unique mappings or multiple mappings of SGS data are required. BatMis is written in C/C++ and is freely available from http://code.google.com/p/batmis/

Multiple sequence alignment using multi-objective based bacterial foraging optimization algorithm.

PubMed

Rani, R Ranjani; Ramyachitra, D

2016-12-01

Multiple sequence alignment (MSA) is a widespread approach in computational biology and bioinformatics. MSA deals with how the sequences of nucleotides and amino acids are sequenced with possible alignment and minimum number of gaps between them, which directs to the functional, evolutionary and structural relationships among the sequences. Still the computation of MSA is a challenging task to provide an efficient accuracy and statistically significant results of alignments. In this work, the Bacterial Foraging Optimization Algorithm was employed to align the biological sequences which resulted in a non-dominated optimal solution. It employs Multi-objective, such as: Maximization of Similarity, Non-gap percentage, Conserved blocks and Minimization of gap penalty. BAliBASE 3.0 benchmark database was utilized to examine the proposed algorithm against other methods In this paper, two algorithms have been proposed: Hybrid Genetic Algorithm with Artificial Bee Colony (GA-ABC) and Bacterial Foraging Optimization Algorithm. It was found that Hybrid Genetic Algorithm with Artificial Bee Colony performed better than the existing optimization algorithms. But still the conserved blocks were not obtained using GA-ABC. Then BFO was used for the alignment and the conserved blocks were obtained. The proposed Multi-Objective Bacterial Foraging Optimization Algorithm (MO-BFO) was compared with widely used MSA methods Clustal Omega, Kalign, MUSCLE, MAFFT, Genetic Algorithm (GA), Ant Colony Optimization (ACO), Artificial Bee Colony (ABC), Particle Swarm Optimization (PSO) and Hybrid Genetic Algorithm with Artificial Bee Colony (GA-ABC). The final results show that the proposed MO-BFO algorithm yields better alignment than most widely used methods. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Taxonaut: an application software for comparative display of multiple taxonomies with a use case of GBIF Species API.

PubMed

Ytow, Nozomi

2016-01-01

The Species API of the Global Biodiversity Information Facility (GBIF) provides public access to taxonomic data aggregated from multiple data sources. Each data source follows its own classification which can be inconsistent with classifications from other sources. Even with a reference classification e.g. the GBIF Backbone taxonomy, a comprehensive method to compare classifications in the data aggregation is essential, especially for non-expert users. A Java application was developed to compare multiple taxonomies graphically using classification data acquired from GBIF's ChecklistBank via the GBIF Species API. It uses a table to display taxonomies where each column represents a taxonomy under comparison, with an aligner column to organise taxa by name. Each cell contains the name of a taxon if the classification in that column contains the name. Each column also has a cell showing the hierarchy of the taxonomy by a folder metaphor where taxa are aligned and synchronised in the aligner column. A set of those comparative tables shows taxa categorised by relationship between taxonomies. The result set is also available as tables in an Excel format file.

Parental alignments and rejection: an empirical study of alienation in children of divorce.

PubMed

Johnston, Janet R

2003-01-01

This study of family relationships after divorce examined the frequency and extent of child-parent alignments and correlates of children's rejection of a parent, these being basic components of the controversial idea of "parental alienation syndrome." The sample consisted of 215 children from the family courts and general community two to three years after parental separation. The findings indicate that children's attitudes toward their parents range from positive to negative, with relatively few being extremely aligned or rejecting. Rejection of a parent has multiple determinants, with both the aligned and rejected parents contributing to the problem, in addition to vulnerabilities within children themselves.

Parallel alignment of bacteria using near-field optical force array for cell sorting

NASA Astrophysics Data System (ADS)

Zhao, H. T.; Zhang, Y.; Chin, L. K.; Yap, P. H.; Wang, K.; Ser, W.; Liu, A. Q.

2017-08-01

This paper presents a near-field approach to align multiple rod-shaped bacteria based on the interference pattern in silicon nano-waveguide arrays. The bacteria in the optical field will be first trapped by the gradient force and then rotated by the scattering force to the equilibrium position. In the experiment, the Shigella bacteria is rotated 90 deg and aligned to horizontal direction in 9.4 s. Meanwhile, 150 Shigella is trapped on the surface in 5 min and 86% is aligned with angle < 5 deg. This method is a promising toolbox for the research of parallel single-cell biophysical characterization, cell-cell interaction, etc.

AlignMiner: a Web-based tool for detection of divergent regions in multiple sequence alignments of conserved sequences

PubMed Central

2010-01-01

Background Multiple sequence alignments are used to study gene or protein function, phylogenetic relations, genome evolution hypotheses and even gene polymorphisms. Virtually without exception, all available tools focus on conserved segments or residues. Small divergent regions, however, are biologically important for specific quantitative polymerase chain reaction, genotyping, molecular markers and preparation of specific antibodies, and yet have received little attention. As a consequence, they must be selected empirically by the researcher. AlignMiner has been developed to fill this gap in bioinformatic analyses. Results AlignMiner is a Web-based application for detection of conserved and divergent regions in alignments of conserved sequences, focusing particularly on divergence. It accepts alignments (protein or nucleic acid) obtained using any of a variety of algorithms, which does not appear to have a significant impact on the final results. AlignMiner uses different scoring methods for assessing conserved/divergent regions, Entropy being the method that provides the highest number of regions with the greatest length, and Weighted being the most restrictive. Conserved/divergent regions can be generated either with respect to the consensus sequence or to one master sequence. The resulting data are presented in a graphical interface developed in AJAX, which provides remarkable user interaction capabilities. Users do not need to wait until execution is complete and can.even inspect their results on a different computer. Data can be downloaded onto a user disk, in standard formats. In silico and experimental proof-of-concept cases have shown that AlignMiner can be successfully used to designing specific polymerase chain reaction primers as well as potential epitopes for antibodies. Primer design is assisted by a module that deploys several oligonucleotide parameters for designing primers "on the fly". Conclusions AlignMiner can be used to reliably detect divergent regions via several scoring methods that provide different levels of selectivity. Its predictions have been verified by experimental means. Hence, it is expected that its usage will save researchers' time and ensure an objective selection of the best-possible divergent region when closely related sequences are analysed. AlignMiner is freely available at http://www.scbi.uma.es/alignminer. PMID:20525162

Fine-tuning structural RNA alignments in the twilight zone.

PubMed

Bremges, Andreas; Schirmer, Stefanie; Giegerich, Robert

2010-04-30

A widely used method to find conserved secondary structure in RNA is to first construct a multiple sequence alignment, and then fold the alignment, optimizing a score based on thermodynamics and covariance. This method works best around 75% sequence similarity. However, in a "twilight zone" below 55% similarity, the sequence alignment tends to obscure the covariance signal used in the second phase. Therefore, while the overall shape of the consensus structure may still be found, the degree of conservation cannot be estimated reliably. Based on a combination of available methods, we present a method named planACstar for improving structure conservation in structural alignments in the twilight zone. After constructing a consensus structure by alignment folding, planACstar abandons the original sequence alignment, refolds the sequences individually, but consistent with the consensus, aligns the structures, irrespective of sequence, by a pure structure alignment method, and derives an improved sequence alignment from the alignment of structures, to be re-submitted to alignment folding, etc.. This circle may be iterated as long as structural conservation improves, but normally, one step suffices. Employing the tools ClustalW, RNAalifold, and RNAforester, we find that for sequences with 30-55% sequence identity, structural conservation can be improved by 10% on average, with a large variation, measured in terms of RNAalifold's own criterion, the structure conservation index.

Increased alignment sensitivity improves the usage of genome alignments for comparative gene annotation.

PubMed

Sharma, Virag; Hiller, Michael

2017-08-21

Genome alignments provide a powerful basis to transfer gene annotations from a well-annotated reference genome to many other aligned genomes. The completeness of these annotations crucially depends on the sensitivity of the underlying genome alignment. Here, we investigated the impact of the genome alignment parameters and found that parameters with a higher sensitivity allow the detection of thousands of novel alignments between orthologous exons that have been missed before. In particular, comparisons between species separated by an evolutionary distance of >0.75 substitutions per neutral site, like human and other non-placental vertebrates, benefit from increased sensitivity. To systematically test if increased sensitivity improves comparative gene annotations, we built a multiple alignment of 144 vertebrate genomes and used this alignment to map human genes to the other 143 vertebrates with CESAR. We found that higher alignment sensitivity substantially improves the completeness of comparative gene annotations by adding on average 2382 and 7440 novel exons and 117 and 317 novel genes for mammalian and non-mammalian species, respectively. Our results suggest a more sensitive alignment strategy that should generally be used for genome alignments between distantly-related species. Our 144-vertebrate genome alignment and the comparative gene annotations (https://bds.mpi-cbg.de/hillerlab/144VertebrateAlignment_CESAR/) are a valuable resource for comparative genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Caterpillar Game: A SW-PBIS Aligned Classroom Management System

ERIC Educational Resources Information Center

Floress, Margaret T.; Jacoby, Amber L.

2017-01-01

The Caterpillar Game is a classroom management system that is aligned with School-wide Positive Behavioral Interventions and Supports standards. A single-case, multiple-baseline design was used to evaluate the effects of the Caterpillar Game on disruptive student behavior and teacher praise. Three classrooms were included in the study (preschool,…

Instructional Alignment as a Measure of Teaching Quality

ERIC Educational Resources Information Center

Polikoff, Morgan S.; Porter, Andrew C.

2014-01-01

Recent years have seen the convergence of two major policy streams in U.S. K-12 education: standards/accountability and teacher quality reforms. Work in these areas has led to the creation of multiple measures of teacher quality, including measures of their instructional alignment to standards/assessments, observational and student survey measures…

SEAN: SNP prediction and display program utilizing EST sequence clusters.

PubMed

Huntley, Derek; Baldo, Angela; Johri, Saurabh; Sergot, Marek

2006-02-15

SEAN is an application that predicts single nucleotide polymorphisms (SNPs) using multiple sequence alignments produced from expressed sequence tag (EST) clusters. The algorithm uses rules of sequence identity and SNP abundance to determine the quality of the prediction. A Java viewer is provided to display the EST alignments and predicted SNPs.

A parallel approach of COFFEE objective function to multiple sequence alignment

NASA Astrophysics Data System (ADS)

Zafalon, G. F. D.; Visotaky, J. M. V.; Amorim, A. R.; Valêncio, C. R.; Neves, L. A.; de Souza, R. C. G.; Machado, J. M.

2015-09-01

The computational tools to assist genomic analyzes show even more necessary due to fast increasing of data amount available. With high computational costs of deterministic algorithms for sequence alignments, many works concentrate their efforts in the development of heuristic approaches to multiple sequence alignments. However, the selection of an approach, which offers solutions with good biological significance and feasible execution time, is a great challenge. Thus, this work aims to show the parallelization of the processing steps of MSA-GA tool using multithread paradigm in the execution of COFFEE objective function. The standard objective function implemented in the tool is the Weighted Sum of Pairs (WSP), which produces some distortions in the final alignments when sequences sets with low similarity are aligned. Then, in studies previously performed we implemented the COFFEE objective function in the tool to smooth these distortions. Although the nature of COFFEE objective function implies in the increasing of execution time, this approach presents points, which can be executed in parallel. With the improvements implemented in this work, we can verify the execution time of new approach is 24% faster than the sequential approach with COFFEE. Moreover, the COFFEE multithreaded approach is more efficient than WSP, because besides it is slightly fast, its biological results are better.

Multilayer Microfluidic Devices Created From A Single Photomask

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, Ryan T.; Sheen, Allison M.; Jambovane, Sachin R.

2013-08-28

The time and expense associated with high quality photomask production can discourage the creation of multilayer microfluidic devices, as each layer currently requires a separate photomask. Here we describe an approach in which multilayer microfabricated devices can be created from a single photomask. The separate layers and their corresponding alignment marks are arranged in separate halves of the mask for two layer devices or quadrants for four layer devices. Selective exposure of the photomask features and rotation of the device substrate between exposures result in multiple copies of the devices on each wafer. Subsequent layers are aligned to patterned featuresmore » on the substrate with the same alignment accuracy as when multiple photomasks are used. We demonstrate this approach for fabricating devices employing multilayer soft lithography (MSL) for pneumatic valving. MSL devices containing as many as 5 layers (4 aligned fluidic layers plus a manually aligned control layer) were successfully created using this approach. Device design is also modularized, enabling the presence or absence of features as well as channel heights to be selected independently from one another. The use of a single photomask to create multilayer devices results in a dramatic savings of time and/or money required to advance from device design to completed prototype.« less

7TMRmine: a Web server for hierarchical mining of 7TMR proteins

PubMed Central

Lu, Guoqing; Wang, Zhifang; Jones, Alan M; Moriyama, Etsuko N

2009-01-01

Background Seven-transmembrane region-containing receptors (7TMRs) play central roles in eukaryotic signal transduction. Due to their biomedical importance, thorough mining of 7TMRs from diverse genomes has been an active target of bioinformatics and pharmacogenomics research. The need for new and accurate 7TMR/GPCR prediction tools is paramount with the accelerated rate of acquisition of diverse sequence information. Currently available and often used protein classification methods (e.g., profile hidden Markov Models) are highly accurate for identifying their membership information among already known 7TMR subfamilies. However, these alignment-based methods are less effective for identifying remote similarities, e.g., identifying proteins from highly divergent or possibly new 7TMR families. In this regard, more sensitive (e.g., alignment-free) methods are needed to complement the existing protein classification methods. A better strategy would be to combine different classifiers, from more specific to more sensitive methods, to identify a broader spectrum of 7TMR protein candidates. Description We developed a Web server, 7TMRmine, by integrating alignment-free and alignment-based classifiers specifically trained to identify candidate 7TMR proteins as well as transmembrane (TM) prediction methods. This new tool enables researchers to easily assess the distribution of GPCR functionality in diverse genomes or individual newly-discovered proteins. 7TMRmine is easily customized and facilitates exploratory analysis of diverse genomes. Users can integrate various alignment-based, alignment-free, and TM-prediction methods in any combination and in any hierarchical order. Sixteen classifiers (including two TM-prediction methods) are available on the 7TMRmine Web server. Not only can the 7TMRmine tool be used for 7TMR mining, but also for general TM-protein analysis. Users can submit protein sequences for analysis, or explore pre-analyzed results for multiple genomes. The server currently includes prediction results and the summary statistics for 68 genomes. Conclusion 7TMRmine facilitates the discovery of 7TMR proteins. By combining prediction results from different classifiers in a multi-level filtering process, prioritized sets of 7TMR candidates can be obtained for further investigation. 7TMRmine can be also used as a general TM-protein classifier. Comparisons of TM and 7TMR protein distributions among 68 genomes revealed interesting differences in evolution of these protein families among major eukaryotic phyla. PMID:19538753

Special Focus

PubMed Central

Nawrocki, Eric P.; Burge, Sarah W.

2013-01-01

The development of RNA bioinformatic tools began more than 30 y ago with the description of the Nussinov and Zuker dynamic programming algorithms for single sequence RNA secondary structure prediction. Since then, many tools have been developed for various RNA sequence analysis problems such as homology search, multiple sequence alignment, de novo RNA discovery, read-mapping, and many more. In this issue, we have collected a sampling of reviews and original research that demonstrate some of the many ways bioinformatics is integrated with current RNA biology research. PMID:23948768

Analysis, Characterization, and Loci of the tuf Genes in Lactobacillus and Bifidobacterium Species and Their Direct Application for Species Identification

PubMed Central

Ventura, Marco; Canchaya, Carlos; Meylan, Valèrie; Klaenhammer, Todd R.; Zink, Ralf

2003-01-01

We analyzed the tuf gene, encoding elongation factor Tu, from 33 strains representing 17 Lactobacillus species and 8 Bifidobacterium species. The tuf sequences were aligned and used to infer phylogenesis among species of lactobacilli and bifidobacteria. We demonstrated that the synonymous substitution affecting this gene renders elongation factor Tu a reliable molecular clock for investigating evolutionary distances of lactobacilli and bifidobacteria. In fact, the phylogeny generated by these tuf sequences is consistent with that derived from 16S rRNA analysis. The investigation of a multiple alignment of tuf sequences revealed regions conserved among strains belonging to the same species but distinct from those of other species. PCR primers complementary to these regions allowed species-specific identification of closely related species, such as Lactobacillus casei group members. These tuf gene-based assays developed in this study provide an alternative to present methods for the identification for lactic acid bacterial species. Since a variable number of tuf genes have been described for bacteria, the presence of multiple genes was examined. Southern analysis revealed one tuf gene in the genomes of lactobacilli and bifidobacteria, but the tuf gene was arranged differently in the genomes of these two taxa. Our results revealed that the tuf gene in bifidobacteria is flanked by the same gene constellation as the str operon, as originally reported for Escherichia coli. In contrast, bioinformatic and transcriptional analyses of the DNA region flanking the tuf gene in four Lactobacillus species indicated the same four-gene unit and suggested a novel tuf operon specific for the genus Lactobacillus. PMID:14602655

eHive: An Artificial Intelligence workflow system for genomic analysis

PubMed Central

2010-01-01

Background The Ensembl project produces updates to its comparative genomics resources with each of its several releases per year. During each release cycle approximately two weeks are allocated to generate all the genomic alignments and the protein homology predictions. The number of calculations required for this task grows approximately quadratically with the number of species. We currently support 50 species in Ensembl and we expect the number to continue to grow in the future. Results We present eHive, a new fault tolerant distributed processing system initially designed to support comparative genomic analysis, based on blackboard systems, network distributed autonomous agents, dataflow graphs and block-branch diagrams. In the eHive system a MySQL database serves as the central blackboard and the autonomous agent, a Perl script, queries the system and runs jobs as required. The system allows us to define dataflow and branching rules to suit all our production pipelines. We describe the implementation of three pipelines: (1) pairwise whole genome alignments, (2) multiple whole genome alignments and (3) gene trees with protein homology inference. Finally, we show the efficiency of the system in real case scenarios. Conclusions eHive allows us to produce computationally demanding results in a reliable and efficient way with minimal supervision and high throughput. Further documentation is available at: http://www.ensembl.org/info/docs/eHive/. PMID:20459813

Using Comparative Genomics for Inquiry-Based Learning to Dissect Virulence of Escherichia coli O157:H7 and Yersinia pestis

PubMed Central

Baumler, David J.; Banta, Lois M.; Hung, Kai F.; Schwarz, Jodi A.; Cabot, Eric L.; Glasner, Jeremy D.; Perna, Nicole T.

2012-01-01

Genomics and bioinformatics are topics of increasing interest in undergraduate biological science curricula. Many existing exercises focus on gene annotation and analysis of a single genome. In this paper, we present two educational modules designed to enable students to learn and apply fundamental concepts in comparative genomics using examples related to bacterial pathogenesis. Students first examine alignments of genomes of Escherichia coli O157:H7 strains isolated from three food-poisoning outbreaks using the multiple-genome alignment tool Mauve. Students investigate conservation of virulence factors using the Mauve viewer and by browsing annotations available at the A Systematic Annotation Package for Community Analysis of Genomes database. In the second module, students use an alignment of five Yersinia pestis genomes to analyze single-nucleotide polymorphisms of three genes to classify strains into biovar groups. Students are then given sequences of bacterial DNA amplified from the teeth of corpses from the first and second pandemics of the bubonic plague and asked to classify these new samples. Learning-assessment results reveal student improvement in self-efficacy and content knowledge, as well as students' ability to use BLAST to identify genomic islands and conduct analyses of virulence factors from E. coli O157:H7 or Y. pestis. Each of these educational modules offers educators new ready-to-implement resources for integrating comparative genomic topics into their curricula. PMID:22383620

Influenza Virus Database (IVDB): an integrated information resource and analysis platform for influenza virus research.

PubMed

Chang, Suhua; Zhang, Jiajie; Liao, Xiaoyun; Zhu, Xinxing; Wang, Dahai; Zhu, Jiang; Feng, Tao; Zhu, Baoli; Gao, George F; Wang, Jian; Yang, Huanming; Yu, Jun; Wang, Jing

2007-01-01

Frequent outbreaks of highly pathogenic avian influenza and the increasing data available for comparative analysis require a central database specialized in influenza viruses (IVs). We have established the Influenza Virus Database (IVDB) to integrate information and create an analysis platform for genetic, genomic, and phylogenetic studies of the virus. IVDB hosts complete genome sequences of influenza A virus generated by Beijing Institute of Genomics (BIG) and curates all other published IV sequences after expert annotation. Our Q-Filter system classifies and ranks all nucleotide sequences into seven categories according to sequence content and integrity. IVDB provides a series of tools and viewers for comparative analysis of the viral genomes, genes, genetic polymorphisms and phylogenetic relationships. A search system has been developed for users to retrieve a combination of different data types by setting search options. To facilitate analysis of global viral transmission and evolution, the IV Sequence Distribution Tool (IVDT) has been developed to display the worldwide geographic distribution of chosen viral genotypes and to couple genomic data with epidemiological data. The BLAST, multiple sequence alignment and phylogenetic analysis tools were integrated for online data analysis. Furthermore, IVDB offers instant access to pre-computed alignments and polymorphisms of IV genes and proteins, and presents the results as SNP distribution plots and minor allele distributions. IVDB is publicly available at http://influenza.genomics.org.cn.

PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes

PubMed Central

Fong, Christine; Rohmer, Laurence; Radey, Matthew; Wasnick, Michael; Brittnacher, Mitchell J

2008-01-01

Background The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT) is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes. Results PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function. Conclusion PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any web browser with no client side software setup or installation required. Source code is freely available to researchers interested in setting up a local version of PSAT for analysis of genomes not available through the public server. Access to the public web server and instructions for obtaining source code can be found at . PMID:18366802

Improvements on a privacy-protection algorithm for DNA sequences with generalization lattices.

PubMed

Li, Guang; Wang, Yadong; Su, Xiaohong

2012-10-01

When developing personal DNA databases, there must be an appropriate guarantee of anonymity, which means that the data cannot be related back to individuals. DNA lattice anonymization (DNALA) is a successful method for making personal DNA sequences anonymous. However, it uses time-consuming multiple sequence alignment and a low-accuracy greedy clustering algorithm. Furthermore, DNALA is not an online algorithm, and so it cannot quickly return results when the database is updated. This study improves the DNALA method. Specifically, we replaced the multiple sequence alignment in DNALA with global pairwise sequence alignment to save time, and we designed a hybrid clustering algorithm comprised of a maximum weight matching (MWM)-based algorithm and an online algorithm. The MWM-based algorithm is more accurate than the greedy algorithm in DNALA and has the same time complexity. The online algorithm can process data quickly when the database is updated. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

GASP: Gapped Ancestral Sequence Prediction for proteins

PubMed Central

Edwards, Richard J; Shields, Denis C

2004-01-01

Background The prediction of ancestral protein sequences from multiple sequence alignments is useful for many bioinformatics analyses. Predicting ancestral sequences is not a simple procedure and relies on accurate alignments and phylogenies. Several algorithms exist based on Maximum Parsimony or Maximum Likelihood methods but many current implementations are unable to process residues with gaps, which may represent insertion/deletion (indel) events or sequence fragments. Results Here we present a new algorithm, GASP (Gapped Ancestral Sequence Prediction), for predicting ancestral sequences from phylogenetic trees and the corresponding multiple sequence alignments. Alignments may be of any size and contain gaps. GASP first assigns the positions of gaps in the phylogeny before using a likelihood-based approach centred on amino acid substitution matrices to assign ancestral amino acids. Important outgroup information is used by first working down from the tips of the tree to the root, using descendant data only to assign probabilities, and then working back up from the root to the tips using descendant and outgroup data to make predictions. GASP was tested on a number of simulated datasets based on real phylogenies. Prediction accuracy for ungapped data was similar to three alternative algorithms tested, with GASP performing better in some cases and worse in others. Adding simple insertions and deletions to the simulated data did not have a detrimental effect on GASP accuracy. Conclusions GASP (Gapped Ancestral Sequence Prediction) will predict ancestral sequences from multiple protein alignments of any size. Although not as accurate in all cases as some of the more sophisticated maximum likelihood approaches, it can process a wide range of input phylogenies and will predict ancestral sequences for gapped and ungapped residues alike. PMID:15350199

IUS prerelease alignment

NASA Technical Reports Server (NTRS)

Evans, F. A.

1978-01-01

Space shuttle orbiter/IUS alignment transfer was evaluated. Although the orbiter alignment accuracy was originally believed to be the major contributor to the overall alignment transfer error, it was shown that orbiter alignment accuracy is not a factor affecting IUS alignment accuracy, if certain procedures are followed. Results are reported of alignment transfer accuracy analysis.

NoFold: RNA structure clustering without folding or alignment.

PubMed

Middleton, Sarah A; Kim, Junhyong

2014-11-01

Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. © 2014 Middleton and Kim; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albrecht, Simon; Winn, Joshua N.; Marcy, Geoffrey W.

We measure the sky-projected stellar obliquities ({lambda}) in the multiple-transiting planetary systems KOI-94 and Kepler-25, using the Rossiter-McLaughlin effect. In both cases, the host stars are well aligned with the orbital planes of the planets. For KOI-94 we find {lambda} = -11 Degree-Sign {+-} 11 Degree-Sign , confirming a recent result by Hirano and coworkers. Kepler-25 was a more challenging case, because the transit depth is unusually small (0.13%). To obtain the obliquity, it was necessary to use prior knowledge of the star's projected rotation rate and apply two different analysis methods to independent wavelength regions of the spectra. Themore » two methods gave consistent results, {lambda} = 7 Degree-Sign {+-} 8 Degree-Sign and -0. Degree-Sign 5 {+-} 5. Degree-Sign 7. There are now a total of five obliquity measurements for host stars of systems of multiple-transiting planets, all of which are consistent with spin-orbit alignment. This alignment is unlikely to be the result of tidal interactions because of the relatively large orbital distances and low planetary masses in the systems. In this respect, the multiplanet host stars differ from hot-Jupiter host stars, which commonly have large spin-orbit misalignments whenever tidal interactions are weak. In particular, the weak-tide subset of hot-Jupiter hosts has obliquities consistent with an isotropic distribution (p = 0.6), but the multiplanet hosts are incompatible with such a distribution (p {approx} 10{sup -6}). This suggests that high obliquities are confined to hot-Jupiter systems, and provides further evidence that hot-Jupiter formation involves processes that tilt the planetary orbit.« less

Quantiprot - a Python package for quantitative analysis of protein sequences.

PubMed

Konopka, Bogumił M; Marciniak, Marta; Dyrka, Witold

2017-07-17

The field of protein sequence analysis is dominated by tools rooted in substitution matrices and alignments. A complementary approach is provided by methods of quantitative characterization. A major advantage of the approach is that quantitative properties defines a multidimensional solution space, where sequences can be related to each other and differences can be meaningfully interpreted. Quantiprot is a software package in Python, which provides a simple and consistent interface to multiple methods for quantitative characterization of protein sequences. The package can be used to calculate dozens of characteristics directly from sequences or using physico-chemical properties of amino acids. Besides basic measures, Quantiprot performs quantitative analysis of recurrence and determinism in the sequence, calculates distribution of n-grams and computes the Zipf's law coefficient. We propose three main fields of application of the Quantiprot package. First, quantitative characteristics can be used in alignment-free similarity searches, and in clustering of large and/or divergent sequence sets. Second, a feature space defined by quantitative properties can be used in comparative studies of protein families and organisms. Third, the feature space can be used for evaluating generative models, where large number of sequences generated by the model can be compared to actually observed sequences.

The Saccharomyces Genome Database Variant Viewer.

PubMed

Sheppard, Travis K; Hitz, Benjamin C; Engel, Stacia R; Song, Giltae; Balakrishnan, Rama; Binkley, Gail; Costanzo, Maria C; Dalusag, Kyla S; Demeter, Janos; Hellerstedt, Sage T; Karra, Kalpana; Nash, Robert S; Paskov, Kelley M; Skrzypek, Marek S; Weng, Shuai; Wong, Edith D; Cherry, J Michael

2016-01-04

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

PubMed Central

2011-01-01

Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines. Conclusions Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as MSMB-NCOA4, may play functional roles in cancer. PMID:21261984

Amino acid sequence analysis of the annexin super-gene family of proteins.

PubMed

Barton, G J; Newman, R H; Freemont, P S; Crumpton, M J

1991-06-15

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.

Evidence for Widespread Reticulate Evolution within Human Duplicons

PubMed Central

Jackson, Michael S. ; Oliver, Karen ; Loveland, Jane ; Humphray, Sean ; Dunham, Ian ; Rocchi, Mariano ; Viggiano, Luigi ; Park, Jonathan P. ; Hurles, Matthew E. ; Santibanez-Koref, Mauro 

2005-01-01

Approximately 5% of the human genome consists of segmental duplications that can cause genomic mutations and may play a role in gene innovation. Reticulate evolutionary processes, such as unequal crossing-over and gene conversion, are known to occur within specific duplicon families, but the broader contribution of these processes to the evolution of human duplications remains poorly characterized. Here, we use phylogenetic profiling to analyze multiple alignments of 24 human duplicon families that span >8 Mb of DNA. Our results indicate that none of them are evolving independently, with all alignments showing sharp discontinuities in phylogenetic signal consistent with reticulation. To analyze these results in more detail, we have developed a quartet method that estimates the relative contribution of nucleotide substitution and reticulate processes to sequence evolution. Our data indicate that most of the duplications show a highly significant excess of sites consistent with reticulate evolution, compared with the number expected by nucleotide substitution alone, with 15 of 30 alignments showing a >20-fold excess over that expected. Using permutation tests, we also show that at least 5% of the total sequence shares 100% sequence identity because of reticulation, a figure that includes 74 independent tracts of perfect identity >2 kb in length. Furthermore, analysis of a subset of alignments indicates that the density of reticulation events is as high as 1 every 4 kb. These results indicate that phylogenetic relationships within recently duplicated human DNA can be rapidly disrupted by reticulate evolution. This finding has important implications for efforts to finish the human genome sequence, complicates comparative sequence analysis of duplicon families, and could profoundly influence the tempo of gene-family evolution. PMID:16252241

Quantitative Analysis of Complex Glioma Cell Migration on Electrospun Polycaprolactone Using Time-Lapse Microscopy

PubMed Central

Johnson, Jed; Nowicki, M. Oskar; Lee, Carol H.; Chiocca, E. Antonio; Viapiano, Mariano S.; Lawler, Sean E.

2009-01-01

Malignant gliomas are the most common tumors originating within the central nervous system and account for over 15,000 deaths annually in the United States. The median survival for glioblastoma, the most common and aggressive of these tumors, is only 14 months. Therapeutic strategies targeting glioma cells migrating away from the tumor core are currently hampered by the difficulty of reproducing migration in the neural parenchyma in vitro. We utilized a tissue engineering approach to develop a physiologically relevant model of glioma cell migration. This revealed that glioma cells display dramatic differences in migration when challenged by random versus aligned electrospun poly-ɛ-caprolactone nanofibers. Cells on aligned fibers migrated at an effective velocity of 4.2 ± 0.39 μm/h compared to 0.8 ± 0.08 μm/h on random fibers, closely matching in vivo models and prior observations of glioma spread in white versus gray matter. Cells on random fibers exhibited extension along multiple fiber axes that prevented net motion; aligned fibers promoted a fusiform morphology better suited to infiltration. Time-lapse microscopy revealed that the motion of individual cells was complex and was influenced by cell cycle and local topography. Glioma stem cell–containing neurospheres seeded on random fibers did not show cell detachment and retained their original shape; on aligned fibers, cells detached and migrated in the fiber direction over a distance sixfold greater than the perpendicular direction. This chemically and physically flexible model allows time-lapse analysis of glioma cell migration while recapitulating in vivo cell morphology, potentially allowing identification of physiological mediators and pharmacological inhibitors of invasion. PMID:19199562

Psychometric Evaluation of the Overexcitability Questionnaire-Two Applying Bayesian Structural Equation Modeling (BSEM) and Multiple-Group BSEM-Based Alignment with Approximate Measurement Invariance

PubMed Central

De Bondt, Niki; Van Petegem, Peter

2015-01-01

The Overexcitability Questionnaire-Two (OEQ-II) measures the degree and nature of overexcitability, which assists in determining the developmental potential of an individual according to Dabrowski's Theory of Positive Disintegration. Previous validation studies using frequentist confirmatory factor analysis, which postulates exact parameter constraints, led to model rejection and a long series of model modifications. Bayesian structural equation modeling (BSEM) allows the application of zero-mean, small-variance priors for cross-loadings, residual covariances, and differences in measurement parameters across groups, better reflecting substantive theory and leading to better model fit and less overestimation of factor correlations. Our BSEM analysis with a sample of 516 students in higher education yields positive results regarding the factorial validity of the OEQ-II. Likewise, applying BSEM-based alignment with approximate measurement invariance, the absence of non-invariant factor loadings and intercepts across gender is supportive of the psychometric quality of the OEQ-II. Compared to males, females scored significantly higher on emotional and sensual overexcitability, and significantly lower on psychomotor overexcitability. PMID:26733931

Psychometric Evaluation of the Overexcitability Questionnaire-Two Applying Bayesian Structural Equation Modeling (BSEM) and Multiple-Group BSEM-Based Alignment with Approximate Measurement Invariance.

PubMed

De Bondt, Niki; Van Petegem, Peter

2015-01-01

The Overexcitability Questionnaire-Two (OEQ-II) measures the degree and nature of overexcitability, which assists in determining the developmental potential of an individual according to Dabrowski's Theory of Positive Disintegration. Previous validation studies using frequentist confirmatory factor analysis, which postulates exact parameter constraints, led to model rejection and a long series of model modifications. Bayesian structural equation modeling (BSEM) allows the application of zero-mean, small-variance priors for cross-loadings, residual covariances, and differences in measurement parameters across groups, better reflecting substantive theory and leading to better model fit and less overestimation of factor correlations. Our BSEM analysis with a sample of 516 students in higher education yields positive results regarding the factorial validity of the OEQ-II. Likewise, applying BSEM-based alignment with approximate measurement invariance, the absence of non-invariant factor loadings and intercepts across gender is supportive of the psychometric quality of the OEQ-II. Compared to males, females scored significantly higher on emotional and sensual overexcitability, and significantly lower on psychomotor overexcitability.

Superposition and alignment of labeled point clouds.

PubMed

Fober, Thomas; Glinca, Serghei; Klebe, Gerhard; Hüllermeier, Eyke

2011-01-01

Geometric objects are often represented approximately in terms of a finite set of points in three-dimensional euclidean space. In this paper, we extend this representation to what we call labeled point clouds. A labeled point cloud is a finite set of points, where each point is not only associated with a position in three-dimensional space, but also with a discrete class label that represents a specific property. This type of model is especially suitable for modeling biomolecules such as proteins and protein binding sites, where a label may represent an atom type or a physico-chemical property. Proceeding from this representation, we address the question of how to compare two labeled points clouds in terms of their similarity. Using fuzzy modeling techniques, we develop a suitable similarity measure as well as an efficient evolutionary algorithm to compute it. Moreover, we consider the problem of establishing an alignment of the structures in the sense of a one-to-one correspondence between their basic constituents. From a biological point of view, alignments of this kind are of great interest, since mutually corresponding molecular constituents offer important information about evolution and heredity, and can also serve as a means to explain a degree of similarity. In this paper, we therefore develop a method for computing pairwise or multiple alignments of labeled point clouds. To this end, we proceed from an optimal superposition of the corresponding point clouds and construct an alignment which is as much as possible in agreement with the neighborhood structure established by this superposition. We apply our methods to the structural analysis of protein binding sites.

Fine-tuning structural RNA alignments in the twilight zone

PubMed Central

2010-01-01

Background A widely used method to find conserved secondary structure in RNA is to first construct a multiple sequence alignment, and then fold the alignment, optimizing a score based on thermodynamics and covariance. This method works best around 75% sequence similarity. However, in a "twilight zone" below 55% similarity, the sequence alignment tends to obscure the covariance signal used in the second phase. Therefore, while the overall shape of the consensus structure may still be found, the degree of conservation cannot be estimated reliably. Results Based on a combination of available methods, we present a method named planACstar for improving structure conservation in structural alignments in the twilight zone. After constructing a consensus structure by alignment folding, planACstar abandons the original sequence alignment, refolds the sequences individually, but consistent with the consensus, aligns the structures, irrespective of sequence, by a pure structure alignment method, and derives an improved sequence alignment from the alignment of structures, to be re-submitted to alignment folding, etc.. This circle may be iterated as long as structural conservation improves, but normally, one step suffices. Conclusions Employing the tools ClustalW, RNAalifold, and RNAforester, we find that for sequences with 30-55% sequence identity, structural conservation can be improved by 10% on average, with a large variation, measured in terms of RNAalifold's own criterion, the structure conservation index. PMID:20433706

Analysis Tool Web Services from the EMBL-EBI.

PubMed

McWilliam, Hamish; Li, Weizhong; Uludag, Mahmut; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Cowley, Andrew Peter; Lopez, Rodrigo

2013-07-01

Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods.

Analysis Tool Web Services from the EMBL-EBI

PubMed Central

McWilliam, Hamish; Li, Weizhong; Uludag, Mahmut; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Cowley, Andrew Peter; Lopez, Rodrigo

2013-01-01

Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods. PMID:23671338

Prototype of the novel CAMEA concept—A backend for neutron spectrometers

NASA Astrophysics Data System (ADS)

Markó, Márton; Groitl, Felix; Birk, Jonas Okkels; Freeman, Paul Gregory; Lefmann, Kim; Christensen, Niels Bech; Niedermayer, Christof; Jurányi, Fanni; Lass, Jakob; Hansen, Allan; Rønnow, Henrik M.

2018-01-01

The continuous angle multiple energy analysis concept is a backend for both time-of-flight and analyzer-based neutron spectrometers optimized for neutron spectroscopy with highly efficient mapping in the horizontal scattering plane. The design employs a series of several upward scattering analyzer arcs placed behind each other, which are set to different final energies allowing a wide angular coverage with multiple energies recorded simultaneously. For validation of the concept and the model calculations, a prototype was installed at the Swiss neutron source SINQ, Paul Scherrer Institut. The design of the prototype, alignment and calibration procedures, experimental results of background measurements, and proof-of-concept inelastic measurements on LiHoF4 and h-YMnO3 are presented here.

JCoDA: a tool for detecting evolutionary selection.

PubMed

Steinway, Steven N; Dannenfelser, Ruth; Laucius, Christopher D; Hayes, James E; Nayak, Sudhir

2010-05-27

The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda.

JCoDA: a tool for detecting evolutionary selection

PubMed Central

2010-01-01

Background The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. Results JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. Conclusions JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda. PMID:20507581

Molecular differentiation of Russian wild ginseng using mitochondrial nad7 intron 3 region.

PubMed

Li, Guisheng; Cui, Yan; Wang, Hongtao; Kwon, Woo-Saeng; Yang, Deok-Chun

2017-07-01

Cultivated ginseng is often introduced as a substitute and adulterant of Russian wild ginseng due to its lower cost or misidentification caused by similarity in appearance with wild ginseng. The aim of this study is to develop a simple and reliable method to differentiate Russian wild ginseng from cultivated ginseng. The mitochondrial NADH dehydrogenase subunit 7 ( nad 7) intron 3 regions of Russian wild ginseng and Chinese cultivated ginseng were analyzed. Based on the multiple sequence alignment result, a specific primer for Russian wild ginseng was designed by introducing additional mismatch and allele-specific polymerase chain reaction (PCR) was performed for identification of wild ginseng. Real-time allele-specific PCR with endpoint analysis was used for validation of the developed Russian wild ginseng single nucleotide polymorphism (SNP) marker. An SNP site specific to Russian wild ginseng was exploited by multiple alignments of mitochondrial nad 7 intron 3 regions of different ginseng samples. With the SNP-based specific primer, Russian wild ginseng was successfully discriminated from Chinese and Korean cultivated ginseng samples by allele-specific PCR. The reliability and specificity of the SNP marker was validated by checking 20 individuals of Russian wild ginseng samples with real-time allele-specific PCR assay. An effective DNA method for molecular discrimination of Russian wild ginseng from Chinese and Korean cultivated ginseng was developed. The established real-time allele-specific PCR was simple and reliable, and the present method should be a crucial complement of chemical analysis for authentication of Russian wild ginseng.

Cellulose in Cyanobacteria. Origin of Vascular Plant Cellulose Synthase?

PubMed Central

Nobles, David R.; Romanovicz, Dwight K.; Brown, R. Malcolm

2001-01-01

Although cellulose biosynthesis among the cyanobacteria has been suggested previously, we present the first conclusive evidence, to our knowledge, of the presence of cellulose in these organisms. Based on the results of x-ray diffraction, electron microscopy of microfibrils, and cellobiohydrolase I-gold labeling, we report the occurrence of cellulose biosynthesis in nine species representing three of the five sections of cyanobacteria. Sequence analysis of the genomes of four cyanobacteria revealed the presence of multiple amino acid sequences bearing the DDD35QXXRW motif conserved in all cellulose synthases. Pairwise alignments demonstrated that CesAs from plants were more similar to putative cellulose synthases from Anabaena sp. Pasteur Culture Collection 7120 and Nostoc punctiforme American Type Culture Collection 29133 than any other cellulose synthases in the database. Multiple alignments of putative cellulose synthases from Anabaena sp. Pasteur Culture Collection 7120 and N. punctiforme American Type Culture Collection 29133 with the cellulose synthases of other prokaryotes, Arabidopsis, Gossypium hirsutum, Populus alba × Populus tremula, corn (Zea mays), and Dictyostelium discoideum showed that cyanobacteria share an insertion between conserved regions U1 and U2 found previously only in eukaryotic sequences. Furthermore, phylogenetic analysis indicates that the cyanobacterial cellulose synthases share a common branch with CesAs of vascular plants in a manner similar to the relationship observed with cyanobacterial and chloroplast 16s rRNAs, implying endosymbiotic transfer of CesA from cyanobacteria to plants and an ancient origin for cellulose synthase in eukaryotes. PMID:11598227

A scalable architecture for extracting, aligning, linking, and visualizing multi-Int data

NASA Astrophysics Data System (ADS)

Knoblock, Craig A.; Szekely, Pedro

2015-05-01

An analyst today has a tremendous amount of data available, but each of the various data sources typically exists in their own silos, so an analyst has limited ability to see an integrated view of the data and has little or no access to contextual information that could help in understanding the data. We have developed the Domain-Insight Graph (DIG) system, an innovative architecture for extracting, aligning, linking, and visualizing massive amounts of domain-specific content from unstructured sources. Under the DARPA Memex program we have already successfully applied this architecture to multiple application domains, including the enormous international problem of human trafficking, where we extracted, aligned and linked data from 50 million online Web pages. DIG builds on our Karma data integration toolkit, which makes it easy to rapidly integrate structured data from a variety of sources, including databases, spreadsheets, XML, JSON, and Web services. The ability to integrate Web services allows Karma to pull in live data from the various social media sites, such as Twitter, Instagram, and OpenStreetMaps. DIG then indexes the integrated data and provides an easy to use interface for query, visualization, and analysis.

Towards Long-Range RNA Structure Prediction in Eukaryotic Genes.

PubMed

Pervouchine, Dmitri D

2018-06-15

The ability to form an intramolecular structure plays a fundamental role in eukaryotic RNA biogenesis. Proximate regions in the primary transcripts fold into a local secondary structure, which is then hierarchically assembled into a tertiary structure that is stabilized by RNA-binding proteins and long-range intramolecular base pairings. While the local RNA structure can be predicted reasonably well for short sequences, long-range structure at the scale of eukaryotic genes remains problematic from the computational standpoint. The aim of this review is to list functional examples of long-range RNA structures, to summarize current comparative methods of structure prediction, and to highlight their advances and limitations in the context of long-range RNA structures. Most comparative methods implement the “first-align-then-fold” principle, i.e., they operate on multiple sequence alignments, while functional RNA structures often reside in non-conserved parts of the primary transcripts. The opposite “first-fold-then-align” approach is currently explored to a much lesser extent. Developing novel methods in both directions will improve the performance of comparative RNA structure analysis and help discover novel long-range structures, their higher-order organization, and RNA⁻RNA interactions across the transcriptome.

R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server

PubMed Central

Cannone, Jamie J.; Sweeney, Blake A.; Petrov, Anton I.; Gutell, Robin R.; Zirbel, Craig L.; Leontis, Neocles

2015-01-01

The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. PMID:26048960

Hidden Markov models of biological primary sequence information.

PubMed Central

Baldi, P; Chauvin, Y; Hunkapiller, T; McClure, M A

1994-01-01

Hidden Markov model (HMM) techniques are used to model families of biological sequences. A smooth and convergent algorithm is introduced to iteratively adapt the transition and emission parameters of the models from the examples in a given family. The HMM approach is applied to three protein families: globins, immunoglobulins, and kinases. In all cases, the models derived capture the important statistical characteristics of the family and can be used for a number of tasks, including multiple alignments, motif detection, and classification. For K sequences of average length N, this approach yields an effective multiple-alignment algorithm which requires O(KN2) operations, linear in the number of sequences. PMID:8302831

Gemi: PCR Primers Prediction from Multiple Alignments

PubMed Central

Sobhy, Haitham; Colson, Philippe

2012-01-01

Designing primers and probes for polymerase chain reaction (PCR) is a preliminary and critical step that requires the identification of highly conserved regions in a given set of sequences. This task can be challenging if the targeted sequences display a high level of diversity, as frequently encountered in microbiologic studies. We developed Gemi, an automated, fast, and easy-to-use bioinformatics tool with a user-friendly interface to design primers and probes based on multiple aligned sequences. This tool can be used for the purpose of real-time and conventional PCR and can deal efficiently with large sets of sequences of a large size. PMID:23316117

Open-Phylo: a customizable crowd-computing platform for multiple sequence alignment

PubMed Central

2013-01-01

Citizen science games such as Galaxy Zoo, Foldit, and Phylo aim to harness the intelligence and processing power generated by crowds of online gamers to solve scientific problems. However, the selection of the data to be analyzed through these games is under the exclusive control of the game designers, and so are the results produced by gamers. Here, we introduce Open-Phylo, a freely accessible crowd-computing platform that enables any scientist to enter our system and use crowds of gamers to assist computer programs in solving one of the most fundamental problems in genomics: the multiple sequence alignment problem. PMID:24148814

Taxonaut: an application software for comparative display of multiple taxonomies with a use case of GBIF Species API

PubMed Central

2016-01-01

Abstract Background The Species API of the Global Biodiversity Information Facility (GBIF) provides public access to taxonomic data aggregated from multiple data sources. Each data source follows its own classification which can be inconsistent with classifications from other sources. Even with a reference classification e.g. the GBIF Backbone taxonomy, a comprehensive method to compare classifications in the data aggregation is essential, especially for non-expert users. New information A Java application was developed to compare multiple taxonomies graphically using classification data acquired from GBIF’s ChecklistBank via the GBIF Species API. It uses a table to display taxonomies where each column represents a taxonomy under comparison, with an aligner column to organise taxa by name. Each cell contains the name of a taxon if the classification in that column contains the name. Each column also has a cell showing the hierarchy of the taxonomy by a folder metaphor where taxa are aligned and synchronised in the aligner column. A set of those comparative tables shows taxa categorised by relationship between taxonomies. The result set is also available as tables in an Excel format file. PMID:27932916

Combining multiple thresholding binarization values to improve OCR output

NASA Astrophysics Data System (ADS)

Lund, William B.; Kennard, Douglas J.; Ringger, Eric K.

2013-01-01

For noisy, historical documents, a high optical character recognition (OCR) word error rate (WER) can render the OCR text unusable. Since image binarization is often the method used to identify foreground pixels, a body of research seeks to improve image-wide binarization directly. Instead of relying on any one imperfect binarization technique, our method incorporates information from multiple simple thresholding binarizations of the same image to improve text output. Using a new corpus of 19th century newspaper grayscale images for which the text transcription is known, we observe WERs of 13.8% and higher using current binarization techniques and a state-of-the-art OCR engine. Our novel approach combines the OCR outputs from multiple thresholded images by aligning the text output and producing a lattice of word alternatives from which a lattice word error rate (LWER) is calculated. Our results show a LWER of 7.6% when aligning two threshold images and a LWER of 6.8% when aligning five. From the word lattice we commit to one hypothesis by applying the methods of Lund et al. (2011) achieving an improvement over the original OCR output and a 8.41% WER result on this data set.

Line Up, Line Up: Using Technology to Align and Enhance Peer Learning and Assessment in a Student Centred Foundation Organic Chemistry Module

ERIC Educational Resources Information Center

Ryan, Barry J.

2013-01-01

This paper describes how three technologies were utilised in combination to align student learning and assessment as part of a case study. Multiple choice questions (MCQs) were central to all these technologies. The peer learning technologies; Personal Response Devices (a.k.a. "Clickers") and "PeerWise"…

System and method for detecting components of a mixture including tooth elements for alignment

DOEpatents

Sommer, Gregory Jon; Schaff, Ulrich Y.

2016-11-22

Examples are described including assay platforms having tooth elements. An impinging element may sequentially engage tooth elements on the assay platform to sequentially align corresponding detection regions with a detection unit. In this manner, multiple measurements may be made of detection regions on the assay platform without necessarily requiring the starting and stopping of a motor.

Aligning Metabolic Pathways Exploiting Binary Relation of Reactions.

PubMed

Huang, Yiran; Zhong, Cheng; Lin, Hai Xiang; Huang, Jing

2016-01-01

Metabolic pathway alignment has been widely used to find one-to-one and/or one-to-many reaction mappings to identify the alternative pathways that have similar functions through different sets of reactions, which has important applications in reconstructing phylogeny and understanding metabolic functions. The existing alignment methods exhaustively search reaction sets, which may become infeasible for large pathways. To address this problem, we present an effective alignment method for accurately extracting reaction mappings between two metabolic pathways. We show that connected relation between reactions can be formalized as binary relation of reactions in metabolic pathways, and the multiplications of zero-one matrices for binary relations of reactions can be accomplished in finite steps. By utilizing the multiplications of zero-one matrices for binary relation of reactions, we efficiently obtain reaction sets in a small number of steps without exhaustive search, and accurately uncover biologically relevant reaction mappings. Furthermore, we introduce a measure of topological similarity of nodes (reactions) by comparing the structural similarity of the k-neighborhood subgraphs of the nodes in aligning metabolic pathways. We employ this similarity metric to improve the accuracy of the alignments. The experimental results on the KEGG database show that when compared with other state-of-the-art methods, in most cases, our method obtains better performance in the node correctness and edge correctness, and the number of the edges of the largest common connected subgraph for one-to-one reaction mappings, and the number of correct one-to-many reaction mappings. Our method is scalable in finding more reaction mappings with better biological relevance in large metabolic pathways.

FEAST: sensitive local alignment with multiple rates of evolution.

PubMed

Hudek, Alexander K; Brown, Daniel G

2011-01-01

We present a pairwise local aligner, FEAST, which uses two new techniques: a sensitive extension algorithm for identifying homologous subsequences, and a descriptive probabilistic alignment model. We also present a new procedure for training alignment parameters and apply it to the human and mouse genomes, producing a better parameter set for these sequences. Our extension algorithm identifies homologous subsequences by considering all evolutionary histories. It has higher maximum sensitivity than Viterbi extensions, and better balances specificity. We model alignments with several submodels, each with unique statistical properties, describing strongly similar and weakly similar regions of homologous DNA. Training parameters using two submodels produces superior alignments, even when we align with only the parameters from the weaker submodel. Our extension algorithm combined with our new parameter set achieves sensitivity 0.59 on synthetic tests. In contrast, LASTZ with default settings achieves sensitivity 0.35 with the same false positive rate. Using the weak submodel as parameters for LASTZ increases its sensitivity to 0.59 with high error. FEAST is available at http://monod.uwaterloo.ca/feast/.

Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data

PubMed Central

Bean, Heather D.; Hill, Jane E.; Dimandja, Jean-Marie D.

2015-01-01

The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly- resolved peaks, especially those at the extremes of the detector linear range, and no influence on well- chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. PMID:25857541

TCW: Transcriptome Computational Workbench

PubMed Central

Soderlund, Carol; Nelson, William; Willer, Mark; Gang, David R.

2013-01-01

Background The analysis of transcriptome data involves many steps and various programs, along with organization of large amounts of data and results. Without a methodical approach for storage, analysis and query, the resulting ad hoc analysis can lead to human error, loss of data and results, inefficient use of time, and lack of verifiability, repeatability, and extensibility. Methodology The Transcriptome Computational Workbench (TCW) provides Java graphical interfaces for methodical analysis for both single and comparative transcriptome data without the use of a reference genome (e.g. for non-model organisms). The singleTCW interface steps the user through importing transcript sequences (e.g. Illumina) or assembling long sequences (e.g. Sanger, 454, transcripts), annotating the sequences, and performing differential expression analysis using published statistical programs in R. The data, metadata, and results are stored in a MySQL database. The multiTCW interface builds a comparison database by importing sequence and annotation from one or more single TCW databases, executes the ESTscan program to translate the sequences into proteins, and then incorporates one or more clusterings, where the clustering options are to execute the orthoMCL program, compute transitive closure, or import clusters. Both singleTCW and multiTCW allow extensive query and display of the results, where singleTCW displays the alignment of annotation hits to transcript sequences, and multiTCW displays multiple transcript alignments with MUSCLE or pairwise alignments. The query programs can be executed on the desktop for fastest analysis, or from the web for sharing the results. Conclusion It is now affordable to buy a multi-processor machine, and easy to install Java and MySQL. By simply downloading the TCW, the user can interactively analyze, query and view their data. The TCW allows in-depth data mining of the results, which can lead to a better understanding of the transcriptome. TCW is freely available from www.agcol.arizona.edu/software/tcw. PMID:23874959

TCW: transcriptome computational workbench.

PubMed

Soderlund, Carol; Nelson, William; Willer, Mark; Gang, David R

2013-01-01

The analysis of transcriptome data involves many steps and various programs, along with organization of large amounts of data and results. Without a methodical approach for storage, analysis and query, the resulting ad hoc analysis can lead to human error, loss of data and results, inefficient use of time, and lack of verifiability, repeatability, and extensibility. The Transcriptome Computational Workbench (TCW) provides Java graphical interfaces for methodical analysis for both single and comparative transcriptome data without the use of a reference genome (e.g. for non-model organisms). The singleTCW interface steps the user through importing transcript sequences (e.g. Illumina) or assembling long sequences (e.g. Sanger, 454, transcripts), annotating the sequences, and performing differential expression analysis using published statistical programs in R. The data, metadata, and results are stored in a MySQL database. The multiTCW interface builds a comparison database by importing sequence and annotation from one or more single TCW databases, executes the ESTscan program to translate the sequences into proteins, and then incorporates one or more clusterings, where the clustering options are to execute the orthoMCL program, compute transitive closure, or import clusters. Both singleTCW and multiTCW allow extensive query and display of the results, where singleTCW displays the alignment of annotation hits to transcript sequences, and multiTCW displays multiple transcript alignments with MUSCLE or pairwise alignments. The query programs can be executed on the desktop for fastest analysis, or from the web for sharing the results. It is now affordable to buy a multi-processor machine, and easy to install Java and MySQL. By simply downloading the TCW, the user can interactively analyze, query and view their data. The TCW allows in-depth data mining of the results, which can lead to a better understanding of the transcriptome. TCW is freely available from www.agcol.arizona.edu/software/tcw.

GCALIGNER 1.0: an alignment program to compute a multiple sample comparison data matrix from large eco-chemical datasets obtained by GC.

PubMed

Dellicour, Simon; Lecocq, Thomas

2013-10-01

GCALIGNER 1.0 is a computer program designed to perform a preliminary data comparison matrix of chemical data obtained by GC without MS information. The alignment algorithm is based on the comparison between the retention times of each detected compound in a sample. In this paper, we test the GCALIGNER efficiency on three datasets of the chemical secretions of bumble bees. The algorithm performs the alignment with a low error rate (<3%). GCALIGNER 1.0 is a useful, simple and free program based on an algorithm that enables the alignment of table-type data from GC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological intuition in alignment-free methods: response to Posada.

PubMed

Ragan, Mark A; Chan, Cheong Xin

2013-08-01

A recent editorial in Journal of Molecular Evolution highlights opportunities and challenges facing molecular evolution in the era of next-generation sequencing. Abundant sequence data should allow more-complex models to be fit at higher confidence, making phylogenetic inference more reliable and improving our understanding of evolution at the molecular level. However, concern that approaches based on multiple sequence alignment may be computationally infeasible for large datasets is driving the development of so-called alignment-free methods for sequence comparison and phylogenetic inference. The recent editorial characterized these approaches as model-free, not based on the concept of homology, and lacking in biological intuition. We argue here that alignment-free methods have not abandoned models or homology, and can be biologically intuitive.

Viewing multiple sequence alignments with the JavaScript Sequence Alignment Viewer (JSAV)

PubMed Central

Martin, Andrew C. R.

2014-01-01

The JavaScript Sequence Alignment Viewer (JSAV) is designed as a simple-to-use JavaScript component for displaying sequence alignments on web pages. The display of sequences is highly configurable with options to allow alternative coloring schemes, sorting of sequences and ’dotifying’ repeated amino acids. An option is also available to submit selected sequences to another web site, or to other JavaScript code. JSAV is implemented purely in JavaScript making use of the JQuery and JQuery-UI libraries. It does not use any HTML5-specific options to help with browser compatibility. The code is documented using JSDOC and is available from http://www.bioinf.org.uk/software/jsav/. PMID:25653836

Viewing multiple sequence alignments with the JavaScript Sequence Alignment Viewer (JSAV).

PubMed

Martin, Andrew C R

2014-01-01

The JavaScript Sequence Alignment Viewer (JSAV) is designed as a simple-to-use JavaScript component for displaying sequence alignments on web pages. The display of sequences is highly configurable with options to allow alternative coloring schemes, sorting of sequences and 'dotifying' repeated amino acids. An option is also available to submit selected sequences to another web site, or to other JavaScript code. JSAV is implemented purely in JavaScript making use of the JQuery and JQuery-UI libraries. It does not use any HTML5-specific options to help with browser compatibility. The code is documented using JSDOC and is available from http://www.bioinf.org.uk/software/jsav/.

Genome alignment with graph data structures: a comparison

PubMed Central

2014-01-01

Background Recent advances in rapid, low-cost sequencing have opened up the opportunity to study complete genome sequences. The computational approach of multiple genome alignment allows investigation of evolutionarily related genomes in an integrated fashion, providing a basis for downstream analyses such as rearrangement studies and phylogenetic inference. Graphs have proven to be a powerful tool for coping with the complexity of genome-scale sequence alignments. The potential of graphs to intuitively represent all aspects of genome alignments led to the development of graph-based approaches for genome alignment. These approaches construct a graph from a set of local alignments, and derive a genome alignment through identification and removal of graph substructures that indicate errors in the alignment. Results We compare the structures of commonly used graphs in terms of their abilities to represent alignment information. We describe how the graphs can be transformed into each other, and identify and classify graph substructures common to one or more graphs. Based on previous approaches, we compile a list of modifications that remove these substructures. Conclusion We show that crucial pieces of alignment information, associated with inversions and duplications, are not visible in the structure of all graphs. If we neglect vertex or edge labels, the graphs differ in their information content. Still, many ideas are shared among all graph-based approaches. Based on these findings, we outline a conceptual framework for graph-based genome alignment that can assist in the development of future genome alignment tools. PMID:24712884

Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy.

PubMed

González, Carolina; Tabernero, David; Cortese, Maria Francesca; Gregori, Josep; Casillas, Rosario; Riveiro-Barciela, Mar; Godoy, Cristina; Sopena, Sara; Rando, Ariadna; Yll, Marçal; Lopez-Martinez, Rosa; Quer, Josep; Esteban, Rafael; Buti, Maria; Rodríguez-Frías, Francisco

2018-05-21

To detect hyper-conserved regions in the hepatitis B virus (HBV) X gene ( HBX ) 5' region that could be candidates for gene therapy. The study included 27 chronic hepatitis B treatment-naive patients in various clinical stages (from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeAg-negative and HBeAg-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/mL, the HBX 5' end region [nucleotide (nt) 1255-1611] was PCR-amplified and submitted to next-generation sequencing (NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences (haplotypes) obtained by NGS. Conservation at the HBx protein amino acid (aa) level was also analyzed. NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample (2487-9279, IQR 2817). In 14/27 patients (51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region (nt 1255-1286) and the other in the 5' end coding region (nt 1519-1603). This last region coded for a conserved amino acid region (aa 63-76) that partially overlaps a Kunitz-like domain. Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

Cortex-based inter-subject analysis of iEEG and fMRI data sets: application to sustained task-related BOLD and gamma responses.

PubMed

Esposito, Fabrizio; Singer, Neomi; Podlipsky, Ilana; Fried, Itzhak; Hendler, Talma; Goebel, Rainer

2013-02-01

Linking regional metabolic changes with fluctuations in the local electromagnetic fields directly on the surface of the human cerebral cortex is of tremendous importance for a better understanding of detailed brain processes. Functional magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography (iEEG) measure two technically unrelated but spatially and temporally complementary sets of functional descriptions of human brain activity. In order to allow fine-grained spatio-temporal human brain mapping at the population-level, an effective comparative framework for the cortex-based inter-subject analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG recordings of the same patients with epilepsy during alternated intervals of passive movie viewing and music listening to explore the degree of local spatial correspondence and temporal coupling between blood oxygen level dependent (BOLD) fMRI changes and iEEG spectral power modulations across the cortical surface after cortex-based inter-subject alignment. To this purpose, we applied a simple model of the iEEG activity spread around each electrode location and the cortex-based inter-subject alignment procedure to transform discrete iEEG measurements into cortically distributed group patterns by establishing a fine anatomic correspondence of many iEEG cortical sites across multiple subjects. Our results demonstrate the feasibility of a multi-modal inter-subject cortex-based distributed analysis for combining iEEG and fMRI data sets acquired from multiple subjects with the same experimental paradigm but with different iEEG electrode coverage. The proposed iEEG-fMRI framework allows for improved group statistics in a common anatomical space and preserves the dynamic link between the temporal features of the two modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification and analysis of mutational hotspots in oncogenes and tumour suppressors.

PubMed

Baeissa, Hanadi; Benstead-Hume, Graeme; Richardson, Christopher J; Pearl, Frances M G

2017-03-28

The key to interpreting the contribution of a disease-associated mutation in the development and progression of cancer is an understanding of the consequences of that mutation both on the function of the affected protein and on the pathways in which that protein is involved. Protein domains encapsulate function and position-specific domain based analysis of mutations have been shown to help elucidate their phenotypes. In this paper we examine the domain biases in oncogenes and tumour suppressors, and find that their domain compositions substantially differ. Using data from over 30 different cancers from whole-exome sequencing cancer genomic projects we mapped over one million mutations to their respective Pfam domains to identify which domains are enriched in any of three different classes of mutation; missense, indels or truncations. Next, we identified the mutational hotspots within domain families by mapping small mutations to equivalent positions in multiple sequence alignments of protein domainsWe find that gain of function mutations from oncogenes and loss of function mutations from tumour suppressors are normally found in different domain families and when observed in the same domain families, hotspot mutations are located at different positions within the multiple sequence alignment of the domain. By considering hotspots in tumour suppressors and oncogenes independently, we find that there are different specific positions within domain families that are particularly suited to accommodate either a loss or a gain of function mutation. The position is also dependent on the class of mutation.We find rare mutations co-located with well-known functional mutation hotspots, in members of homologous domain superfamilies, and we detect novel mutation hotspots in domain families previously unconnected with cancer. The results of this analysis can be accessed through the MOKCa database (http://strubiol.icr.ac.uk/extra/MOKCa).

PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification.

PubMed

Thomas, Paul D; Kejariwal, Anish; Campbell, Michael J; Mi, Huaiyu; Diemer, Karen; Guo, Nan; Ladunga, Istvan; Ulitsky-Lazareva, Betty; Muruganujan, Anushya; Rabkin, Steven; Vandergriff, Jody A; Doremieux, Olivier

2003-01-01

The PANTHER database was designed for high-throughput analysis of protein sequences. One of the key features is a simplified ontology of protein function, which allows browsing of the database by biological functions. Biologist curators have associated the ontology terms with groups of protein sequences rather than individual sequences. Statistical models (Hidden Markov Models, or HMMs) are built from each of these groups. The advantage of this approach is that new sequences can be automatically classified as they become available. To ensure accurate functional classification, HMMs are constructed not only for families, but also for functionally distinct subfamilies. Multiple sequence alignments and phylogenetic trees, including curator-assigned information, are available for each family. The current version of the PANTHER database includes training sequences from all organisms in the GenBank non-redundant protein database, and the HMMs have been used to classify gene products across the entire genomes of human, and Drosophila melanogaster. The ontology terms and protein families and subfamilies, as well as Drosophila gene c;assifications, can be browsed and searched for free. Due to outstanding contractual obligations, access to human gene classifications and to protein family trees and multiple sequence alignments will temporarily require a nominal registration fee. PANTHER is publicly available on the web at http://panther.celera.com.

The MIGenAS integrated bioinformatics toolkit for web-based sequence analysis

PubMed Central

Rampp, Markus; Soddemann, Thomas; Lederer, Hermann

2006-01-01

We describe a versatile and extensible integrated bioinformatics toolkit for the analysis of biological sequences over the Internet. The web portal offers convenient interactive access to a growing pool of chainable bioinformatics software tools and databases that are centrally installed and maintained by the RZG. Currently, supported tasks comprise sequence similarity searches in public or user-supplied databases, computation and validation of multiple sequence alignments, phylogenetic analysis and protein–structure prediction. Individual tools can be seamlessly chained into pipelines allowing the user to conveniently process complex workflows without the necessity to take care of any format conversions or tedious parsing of intermediate results. The toolkit is part of the Max-Planck Integrated Gene Analysis System (MIGenAS) of the Max Planck Society available at (click ‘Start Toolkit’). PMID:16844980

Alignment of Tractograms As Graph Matching.

PubMed

Olivetti, Emanuele; Sharmin, Nusrat; Avesani, Paolo

2016-01-01

The white matter pathways of the brain can be reconstructed as 3D polylines, called streamlines, through the analysis of diffusion magnetic resonance imaging (dMRI) data. The whole set of streamlines is called tractogram and represents the structural connectome of the brain. In multiple applications, like group-analysis, segmentation, or atlasing, tractograms of different subjects need to be aligned. Typically, this is done with registration methods, that transform the tractograms in order to increase their similarity. In contrast with transformation-based registration methods, in this work we propose the concept of tractogram correspondence, whose aim is to find which streamline of one tractogram corresponds to which streamline in another tractogram, i.e., a map from one tractogram to another. As a further contribution, we propose to use the relational information of each streamline, i.e., its distances from the other streamlines in its own tractogram, as the building block to define the optimal correspondence. We provide an operational procedure to find the optimal correspondence through a combinatorial optimization problem and we discuss its similarity to the graph matching problem. In this work, we propose to represent tractograms as graphs and we adopt a recent inexact sub-graph matching algorithm to approximate the solution of the tractogram correspondence problem. On tractograms generated from the Human Connectome Project dataset, we report experimental evidence that tractogram correspondence, implemented as graph matching, provides much better alignment than affine registration and comparable if not better results than non-linear registration of volumes.

Silicon Alignment Pins: An Easy Way to Realize a Wafer-To-Wafer Alignment

NASA Technical Reports Server (NTRS)

Peralta, Alejandro (Inventor); Gill, John J. (Inventor); Toda, Risaku (Inventor); Lin, Robert H. (Inventor); Jung-Kubiak, Cecile (Inventor); Reck, Theodore (Inventor); Thomas, Bertrand (Inventor); Siles, Jose V. (Inventor); Lee, Choonsup (Inventor); Chattopadhyay, Goutam (Inventor)

2016-01-01

A silicon alignment pin is used to align successive layers of components made in semiconductor chips and/or metallic components to make easier the assembly of devices having a layered structure. The pin is made as a compressible structure which can be squeezed to reduce its outer diameter, have one end fit into a corresponding alignment pocket or cavity defined in a layer of material to be assembled into a layered structure, and then allowed to expand to produce an interference fit with the cavity. The other end can then be inserted into a corresponding cavity defined in a surface of a second layer of material that mates with the first layer. The two layers are in registry when the pin is mated to both. Multiple layers can be assembled to create a multilayer structure. Examples of such devices are presented.

Patterned growth of individual and multiple vertically aligned carbon nanofibers

NASA Astrophysics Data System (ADS)

Merkulov, V. I.; Lowndes, D. H.; Wei, Y. Y.; Eres, G.; Voelkl, E.

2000-06-01

The results of studies of patterned growth of vertically aligned carbon nanofibers (VACNFs) prepared by plasma-enhanced chemical vapor deposition are reported. Nickel (Ni) dots of various diameters and Ni lines with variable widths and shapes were fabricated using electron beam lithography and evaporation, and served for catalytic growth of VACNFs whose structure was determined by high resolution transmission electron microscopy. It is found that upon plasma pre-etching and heating up to 600-700 °C, thin films of Ni break into droplets which initiate the growth of VACNFs. Above a critical dot size multiple droplets are formed, and consequently multiple VACNFs grow from a single evaporated dot. For dot sizes smaller than the critical size only one droplet is formed, resulting in a single VACNF. In the case of a patterned line, the growth mechanism is similar to that from a dot. VACNFs grow along the line, and above a critical linewidth multiple VACNFs are produced across the line. The mechanism of the formation of single and multiple catalyst droplets and subsequently of VACNFs is discussed.

Creating a Culture of Continuous Assessment to Improve Student Learning through Curriculum Review

ERIC Educational Resources Information Center

Kalu, Frances; Dyjur, Patti

2018-01-01

This chapter describes a curriculum review framework that fosters continuous assessment through collaboration with multiple stakeholders, alignment with program level learning outcomes, evaluation based on multiple sources of evidence, and facilitated development of action plans to improve student learning.

Sustainable Survival for adolescents living with HIV: do SDG-aligned provisions reduce potential mortality risk?

PubMed

Cluver, Lucie; Pantelic, Marija; Orkin, Mark; Toska, Elona; Medley, Sally; Sherr, Lorraine

2018-02-01

The Sustainable Development Goals (SDGs) present a groundbreaking global development agenda to protect the most vulnerable. Adolescents living with HIV in Sub-Saharan Africa continue to experience extreme health vulnerabilities, but we know little about the impacts of SDG-aligned provisions on their health. This study tests associations of provisions aligned with five SDGs with potential mortality risks. Clinical and interview data were gathered from N = 1060 adolescents living with HIV in rural and urban South Africa in 2014 to 2015. All ART-initiated adolescents from 53 government health facilities were identified, and traced in their communities to include those defaulting and lost-to-follow-up. Potential mortality risk was assessed as either: viral suppression failure (1000+ copies/ml) using patient file records, or adolescent self-report of diagnosed but untreated tuberculosis or symptomatic pulmonary tuberculosis. SDG-aligned provisions were measured through adolescent interviews. Provisions aligned with SDGs 1&2 (no poverty and zero hunger) were operationalized as access to basic necessities, social protection and food security; An SDG 3-aligned provision (ensure healthy lives) was having a healthy primary caregiver; An SDG 8-aligned provision (employment for all) was employment of a household member; An SDG 16-aligned provision (protection from violence) was protection from physical, sexual or emotional abuse. Research partners included the South African national government, UNICEF and Pediatric and Adolescent Treatment for Africa. 20.8% of adolescents living with HIV had potential mortality risk - i.e. viral suppression failure, symptomatic untreated TB, or both. All SDG-aligned provisions were significantly associated with reduced potential mortality risk: SDG 1&2 (OR 0.599 CI 0.361 to 0.994); SDG 3 (OR 0.577 CI 0.411 to 0.808); SDG 8 (OR 0.602 CI 0.440 to 0.823) and SDG 16 (OR 0.686 CI 0.505 to 0.933). Access to multiple SDG-aligned provisions showed a strongly graded reduction in potential mortality risk: Among adolescents living with HIV, potential mortality risk was 38.5% with access to no SDG-aligned provisions, and 9.3% with access to all four. SDG-aligned provisions across a range of SDGs were associated with reduced potential mortality risk among adolescents living with HIV. Access to multiple provisions has the potential to substantially improve survival, suggesting the value of connecting and combining SDGs in our response to paediatric and adolescent HIV. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Technical Note: Rod phantom analysis for comparison of PET detector sampling and reconstruction methods.

PubMed

Wollenweber, Scott D; Kemp, Brad J

2016-11-01

This investigation aimed to develop a scanner quantification performance methodology and compare multiple metrics between two scanners under different imaging conditions. Most PET scanners are designed to work over a wide dynamic range of patient imaging conditions. Clinical constraints, however, often impact the realization of the entitlement performance for a particular scanner design. Using less injected dose and imaging for a shorter time are often key considerations, all while maintaining "acceptable" image quality and quantitative capability. A dual phantom measurement including resolution inserts was used to measure the effects of in-plane (x, y) and axial (z) system resolution between two PET/CT systems with different block detector crystal dimensions. One of the scanners had significantly thinner slices. Several quantitative measures, including feature contrast recovery, max/min value, and feature profile accuracy were derived from the resulting data and compared between the two scanners and multiple phantoms and alignments. At the clinically relevant count levels used, the scanner with thinner slices had improved performance of approximately 2%, averaged over phantom alignments, measures, and reconstruction methods, for the head-sized phantom, mainly demonstrated with the rods aligned perpendicular to the scanner axis. That same scanner had a slightly decreased performance of -1% for the larger body-size phantom, mostly due to an apparent noise increase in the images. Most of the differences in the metrics between the two scanners were less than 10%. Using the proposed scanner performance methodology, it was shown that smaller detector elements and a larger number of image voxels require higher count density in order to demonstrate improved image quality and quantitation. In a body imaging scenario under typical clinical conditions, the potential advantages of the design must overcome increases in noise due to lower count density.

Multilevel, multicomponent microarchitectures of vertically-aligned carbon nanotubes for diverse applications.

PubMed

Qu, Liangti; Vaia, Rich A; Dai, Liming

2011-02-22

A simple multiple contact transfer technique has been developed for controllable fabrication of multilevel, multicomponent microarchitectures of vertically aligned carbon nanotubes (VA-CNTs). Three dimensional (3-D) multicomponent micropatterns of aligned single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) have been fabricated, which can be used to develop a newly designed touch sensor with reversible electrical responses for potential applications in electronic devices, as demonstrated in this study. The demonstrated dependence of light diffraction on structural transfiguration of the resultant CNT micropattern also indicates their potential for optical devices. Further introduction of various components with specific properties (e.g., ZnO nanorods) into the CNT micropatterns enabled us to tailor such surface characteristics as wettability and light response. Owing to the highly generic nature of the multiple contact transfer strategy, the methodology developed here could provide a general approach for interposing a large variety of multicomponent elements (e.g., nanotubes, nanorods/wires, photonic crystals, etc.) onto a single chip for multifunctional device applications.

Fabricating cooled electronic system with liquid-cooled cold plate and thermal spreader

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chainer, Timothy J.; Graybill, David P.; Iyengar, Madhusudan K.

Methods are provided for facilitating cooling of an electronic component. The method includes providing a liquid-cooled cold plate and a thermal spreader associated with the cold plate. The cold plate includes multiple coolant-carrying channel sections extending within the cold plate, and a thermal conduction surface with a larger surface area than a surface area of the component to be cooled. The thermal spreader includes one or more heat pipes including multiple heat pipe sections. One or more heat pipe sections are partially aligned to a first region of the cold plate, that is, where aligned to the surface to bemore » cooled, and partially aligned to a second region of the cold plate, which is outside the first region. The one or more heat pipes facilitate distribution of heat from the electronic component to coolant-carrying channel sections of the cold plate located in the second region of the cold plate.« less

Fabricating cooled electronic system with liquid-cooled cold plate and thermal spreader

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chainer, Timothy J.; Graybill, David P.; Iyengar, Madhusudan K.

Methods are provided for facilitating cooling of an electronic component. The methods include providing a liquid-cooled cold plate and a thermal spreader associated with the cold plate. The cold plate includes multiple coolant-carrying channel sections extending within the cold plate, and a thermal conduction surface with a larger surface area than a surface area of the component to be cooled. The thermal spreader includes one or more heat pipes including multiple heat pipe sections. One or more heat pipe sections are partially aligned to a first region of the cold plate, that is, where aligned to the surface to bemore » cooled, and partially aligned to a second region of the cold plate, which is outside the first region. The one or more heat pipes facilitate distribution of heat from the electronic component to coolant-carrying channel sections of the cold plate located in the second region of the cold plate.« less

Cooled electronic system with liquid-cooled cold plate and thermal spreader coupled to electronic component

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chainer, Timothy J.; Graybill, David P.; Iyengar, Madhusudan K.

Apparatus and method are provided for facilitating cooling of an electronic component. The apparatus includes a liquid-cooled cold plate and a thermal spreader associated with the cold plate. The cold plate includes multiple coolant-carrying channel sections extending within the cold plate, and a thermal conduction surface with a larger surface area than a surface area of the component to be cooled. The thermal spreader includes one or more heat pipes including multiple heat pipe sections. One or more heat pipe sections are partially aligned to a first region of the cold plate, that is, where aligned to the surface tomore » be cooled, and partially aligned to a second region of the cold plate, which is outside the first region. The one or more heat pipes facilitate distribution of heat from the electronic component to coolant-carrying channel sections of the cold plate located in the second region of the cold plate.« less

Cooled electronic system with liquid-cooled cold plate and thermal spreader coupled to electronic component

DOEpatents

Chainer, Timothy J.; Graybill, David P.; Iyengar, Madhusudan K.; Kamath, Vinod; Kochuparambil, Bejoy J.; Schmidt, Roger R.; Steinke, Mark E.

2016-08-09

Apparatus and method are provided for facilitating cooling of an electronic component. The apparatus includes a liquid-cooled cold plate and a thermal spreader associated with the cold plate. The cold plate includes multiple coolant-carrying channel sections extending within the cold plate, and a thermal conduction surface with a larger surface area than a surface area of the component to be cooled. The thermal spreader includes one or more heat pipes including multiple heat pipe sections. One or more heat pipe sections are partially aligned to a first region of the cold plate, that is, where aligned to the surface to be cooled, and partially aligned to a second region of the cold plate, which is outside the first region. The one or more heat pipes facilitate distribution of heat from the electronic component to coolant-carrying channel sections of the cold plate located in the second region of the cold plate.

Cooled electronic system with liquid-cooled cold plate and thermal spreader coupled to electronic component

DOEpatents

Chainer, Timothy J.; Graybill, David P.; Iyengar, Madhusudan K.; Kamath, Vinod; Kochuparambil, Bejoy J.; Schmidt, Roger R.; Steinke, Mark E.

2016-04-05

Apparatus and method are provided for facilitating cooling of an electronic component. The apparatus includes a liquid-cooled cold plate and a thermal spreader associated with the cold plate. The cold plate includes multiple coolant-carrying channel sections extending within the cold plate, and a thermal conduction surface with a larger surface area than a surface area of the component to be cooled. The thermal spreader includes one or more heat pipes including multiple heat pipe sections. One or more heat pipe sections are partially aligned to a first region of the cold plate, that is, where aligned to the surface to be cooled, and partially aligned to a second region of the cold plate, which is outside the first region. The one or more heat pipes facilitate distribution of heat from the electronic component to coolant-carrying channel sections of the cold plate located in the second region of the cold plate.

Design and implementation of a hybrid MPI-CUDA model for the Smith-Waterman algorithm.

PubMed

Khaled, Heba; Faheem, Hossam El Deen Mostafa; El Gohary, Rania

2015-01-01

This paper provides a novel hybrid model for solving the multiple pair-wise sequence alignment problem combining message passing interface and CUDA, the parallel computing platform and programming model invented by NVIDIA. The proposed model targets homogeneous cluster nodes equipped with similar Graphical Processing Unit (GPU) cards. The model consists of the Master Node Dispatcher (MND) and the Worker GPU Nodes (WGN). The MND distributes the workload among the cluster working nodes and then aggregates the results. The WGN performs the multiple pair-wise sequence alignments using the Smith-Waterman algorithm. We also propose a modified implementation to the Smith-Waterman algorithm based on computing the alignment matrices row-wise. The experimental results demonstrate a considerable reduction in the running time by increasing the number of the working GPU nodes. The proposed model achieved a performance of about 12 Giga cell updates per second when we tested against the SWISS-PROT protein knowledge base running on four nodes.

Retention time alignment of LC/MS data by a divide-and-conquer algorithm.

PubMed

Zhang, Zhongqi

2012-04-01

Liquid chromatography-mass spectrometry (LC/MS) has become the method of choice for characterizing complex mixtures. These analyses often involve quantitative comparison of components in multiple samples. To achieve automated sample comparison, the components of interest must be detected and identified, and their retention times aligned and peak areas calculated. This article describes a simple pairwise iterative retention time alignment algorithm, based on the divide-and-conquer approach, for alignment of ion features detected in LC/MS experiments. In this iterative algorithm, ion features in the sample run are first aligned with features in the reference run by applying a single constant shift of retention time. The sample chromatogram is then divided into two shorter chromatograms, which are aligned to the reference chromatogram the same way. Each shorter chromatogram is further divided into even shorter chromatograms. This process continues until each chromatogram is sufficiently narrow so that ion features within it have a similar retention time shift. In six pairwise LC/MS alignment examples containing a total of 6507 confirmed true corresponding feature pairs with retention time shifts up to five peak widths, the algorithm successfully aligned these features with an error rate of 0.2%. The alignment algorithm is demonstrated to be fast, robust, fully automatic, and superior to other algorithms. After alignment and gap-filling of detected ion features, their abundances can be tabulated for direct comparison between samples.

CAFE: aCcelerated Alignment-FrEe sequence analysis.

PubMed

Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A; Waterman, Michael S; Sun, Fengzhu

2017-07-03

Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, $d_2^*$ and $d_2^S$ are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Skeleton-based human action recognition using multiple sequence alignment

NASA Astrophysics Data System (ADS)

Ding, Wenwen; Liu, Kai; Cheng, Fei; Zhang, Jin; Li, YunSong

2015-05-01

Human action recognition and analysis is an active research topic in computer vision for many years. This paper presents a method to represent human actions based on trajectories consisting of 3D joint positions. This method first decompose action into a sequence of meaningful atomic actions (actionlets), and then label actionlets with English alphabets according to the Davies-Bouldin index value. Therefore, an action can be represented using a sequence of actionlet symbols, which will preserve the temporal order of occurrence of each of the actionlets. Finally, we employ sequence comparison to classify multiple actions through using string matching algorithms (Needleman-Wunsch). The effectiveness of the proposed method is evaluated on datasets captured by commodity depth cameras. Experiments of the proposed method on three challenging 3D action datasets show promising results.

Method for the fabrication of three-dimensional microstructures by deep X-ray lithography

DOEpatents

Sweatt, William C.; Christenson, Todd R.

2005-04-05

A method for the fabrication of three-dimensional microstructures by deep X-ray lithography (DXRL) comprises a masking process that uses a patterned mask with inclined mask holes and off-normal exposures with a DXRL beam aligned with the inclined mask holes. Microstructural features that are oriented in different directions can be obtained by using multiple off-normal exposures through additional mask holes having different orientations. Various methods can be used to block the non-aligned mask holes from the beam when using multiple exposures. A method for fabricating a precision 3D X-ray mask comprises forming an intermediate mask and a master mask on a common support membrane.

A Systolic Array-Based FPGA Parallel Architecture for the BLAST Algorithm

PubMed Central

Guo, Xinyu; Wang, Hong; Devabhaktuni, Vijay

2012-01-01

A design of systolic array-based Field Programmable Gate Array (FPGA) parallel architecture for Basic Local Alignment Search Tool (BLAST) Algorithm is proposed. BLAST is a heuristic biological sequence alignment algorithm which has been used by bioinformatics experts. In contrast to other designs that detect at most one hit in one-clock-cycle, our design applies a Multiple Hits Detection Module which is a pipelining systolic array to search multiple hits in a single-clock-cycle. Further, we designed a Hits Combination Block which combines overlapping hits from systolic array into one hit. These implementations completed the first and second step of BLAST architecture and achieved significant speedup comparing with previously published architectures. PMID:25969747

The Virtual Space Telescope: A New Class of Science Missions

NASA Technical Reports Server (NTRS)

Shah, Neerav; Calhoun, Philip

2016-01-01

Many science investigations proposed by GSFC require two spacecraft alignment across a long distance to form a virtual space telescope. Forming a Virtual Space telescope requires advances in Guidance, Navigation, and Control (GNC) enabling the distribution of monolithic telescopes across multiple space platforms. The capability to align multiple spacecraft to an intertial target is at a low maturity state and we present a roadmap to advance the system-level capability to be flight ready in preparation of various science applications. An engineering proof of concept, called the CANYVAL-X CubeSat MIssion is presented. CANYVAL-X's advancement will decrease risk for a potential starshade mission that would fly with WFIRST.

Generating Models of Surgical Procedures using UMLS Concepts and Multiple Sequence Alignment

PubMed Central

Meng, Frank; D’Avolio, Leonard W.; Chen, Andrew A.; Taira, Ricky K.; Kangarloo, Hooshang

2005-01-01

Surgical procedures can be viewed as a process composed of a sequence of steps performed on, by, or with the patient’s anatomy. This sequence is typically the pattern followed by surgeons when generating surgical report narratives for documenting surgical procedures. This paper describes a methodology for semi-automatically deriving a model of conducted surgeries, utilizing a sequence of derived Unified Medical Language System (UMLS) concepts for representing surgical procedures. A multiple sequence alignment was computed from a collection of such sequences and was used for generating the model. These models have the potential of being useful in a variety of informatics applications such as information retrieval and automatic document generation. PMID:16779094

R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

PubMed

Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

2015-07-01

The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Highly Enhanced Gas Adsorption Properties in Vertically Aligned MoS2 Layers.

PubMed

Cho, Soo-Yeon; Kim, Seon Joon; Lee, Youhan; Kim, Jong-Seon; Jung, Woo-Bin; Yoo, Hae-Wook; Kim, Jihan; Jung, Hee-Tae

2015-09-22

In this work, we demonstrate that gas adsorption is significantly higher in edge sites of vertically aligned MoS2 compared to that of the conventional basal plane exposed MoS2 films. To compare the effect of the alignment of MoS2 on the gas adsorption properties, we synthesized three distinct MoS2 films with different alignment directions ((1) horizontally aligned MoS2 (basal plane exposed), (2) mixture of horizontally aligned MoS2 and vertically aligned layers (basal and edge exposed), and (3) vertically aligned MoS2 (edge exposed)) by using rapid sulfurization method of CVD process. Vertically aligned MoS2 film shows about 5-fold enhanced sensitivity to NO2 gas molecules compared to horizontally aligned MoS2 film. Vertically aligned MoS2 has superior resistance variation compared to horizontally aligned MoS2 even with same surface area exposed to identical concentration of gas molecules. We found that electrical response to target gas molecules correlates directly with the density of the exposed edge sites of MoS2 due to high adsorption of gas molecules onto edge sites of vertically aligned MoS2. Density functional theory (DFT) calculations corroborate the experimental results as stronger NO2 binding energies are computed for multiple configurations near the edge sites of MoS2, which verifies that electrical response to target gas molecules (NO2) correlates directly with the density of the exposed edge sites of MoS2 due to high adsorption of gas molecules onto edge sites of vertically aligned MoS2. We believe that this observation extends to other 2D TMD materials as well as MoS2 and can be applied to significantly enhance the gas sensor performance in these materials.

DAMBE7: New and Improved Tools for Data Analysis in Molecular Biology and Evolution.

PubMed

Xia, Xuhua

2018-06-01

DAMBE is a comprehensive software package for genomic and phylogenetic data analysis on Windows, Linux, and Macintosh computers. New functions include imputing missing distances and phylogeny simultaneously (paving the way to build large phage and transposon trees), new bootstrapping/jackknifing methods for PhyPA (phylogenetics from pairwise alignments), and an improved function for fast and accurate estimation of the shape parameter of the gamma distribution for fitting rate heterogeneity over sites. Previous method corrects multiple hits for each site independently. DAMBE's new method uses all sites simultaneously for correction. DAMBE, featuring a user-friendly graphic interface, is freely available from http://dambe.bio.uottawa.ca (last accessed, April 17, 2018).

Phylo: A Citizen Science Approach for Improving Multiple Sequence Alignment

PubMed Central

Kam, Alfred; Kwak, Daniel; Leung, Clarence; Wu, Chu; Zarour, Eleyine; Sarmenta, Luis; Blanchette, Mathieu; Waldispühl, Jérôme

2012-01-01

Background Comparative genomics, or the study of the relationships of genome structure and function across different species, offers a powerful tool for studying evolution, annotating genomes, and understanding the causes of various genetic disorders. However, aligning multiple sequences of DNA, an essential intermediate step for most types of analyses, is a difficult computational task. In parallel, citizen science, an approach that takes advantage of the fact that the human brain is exquisitely tuned to solving specific types of problems, is becoming increasingly popular. There, instances of hard computational problems are dispatched to a crowd of non-expert human game players and solutions are sent back to a central server. Methodology/Principal Findings We introduce Phylo, a human-based computing framework applying “crowd sourcing” techniques to solve the Multiple Sequence Alignment (MSA) problem. The key idea of Phylo is to convert the MSA problem into a casual game that can be played by ordinary web users with a minimal prior knowledge of the biological context. We applied this strategy to improve the alignment of the promoters of disease-related genes from up to 44 vertebrate species. Since the launch in November 2010, we received more than 350,000 solutions submitted from more than 12,000 registered users. Our results show that solutions submitted contributed to improving the accuracy of up to 70% of the alignment blocks considered. Conclusions/Significance We demonstrate that, combined with classical algorithms, crowd computing techniques can be successfully used to help improving the accuracy of MSA. More importantly, we show that an NP-hard computational problem can be embedded in casual game that can be easily played by people without significant scientific training. This suggests that citizen science approaches can be used to exploit the billions of “human-brain peta-flops” of computation that are spent every day playing games. Phylo is available at: http://phylo.cs.mcgill.ca. PMID:22412834

eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics.

PubMed

Domingo-Almenara, Xavier; Brezmes, Jesus; Vinaixa, Maria; Samino, Sara; Ramirez, Noelia; Ramon-Krauel, Marta; Lerin, Carles; Díaz, Marta; Ibáñez, Lourdes; Correig, Xavier; Perera-Lluna, Alexandre; Yanes, Oscar

2016-10-04

Gas chromatography coupled to mass spectrometry (GC/MS) has been a long-standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ionization (EI). However, the use of GC-EI MS in untargeted metabolomics produces large and complex data sets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information on metabolites across multiple biological samples, integrated computational workflows for data processing are needed. Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC/MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), (iii) alignment of mass spectra across samples, (iv) missing compound recovery, and (v) identification of metabolites by spectral library matching using publicly available mass spectra. eRah outputs a table with compound names, matching scores and the integrated area of compounds for each sample. The automated capabilities of eRah are demonstrated by the analysis of GC-time-of-flight (TOF) MS data from plasma samples of adolescents with hyperinsulinaemic androgen excess and healthy controls. The quantitative results of eRah are compared to centWave, the peak-picking algorithm implemented in the widely used XCMS package, MetAlign, and ChromaTOF software. Significantly dysregulated metabolites are further validated using pure standards and targeted analysis by GC-triple quadrupole (QqQ) MS, LC-QqQ, and NMR. eRah is freely available at http://CRAN.R-project.org/package=erah .

Controllable growth of vertically aligned graphene on C-face SiC

DOE PAGES

Liu, Yu; Chen, Lianlian; Hilliard, Donovan; ...

2016-10-06

We investigated how to control the growth of vertically aligned graphene on C-face SiC by varying the processing conditions. It is found that, the growth rate scales with the annealing temperature and the graphene height is proportional to the annealing time. Temperature gradient and crystalline quality of the SiC substrates influence their vaporization. The partial vapor pressure is crucial as it can interfere with further vaporization. A growth mechanism is proposed in terms of physical vapor transport. The monolayer character of vertically aligned graphene is verified by Raman and X-ray absorption spectroscopy. With the processed samples, d 0 magnetism ismore » realized and negative magnetoresistance is observed after Cu implantation. We also prove that multiple carriers exist in vertically aligned graphene.« less

Controllable growth of vertically aligned graphene on C-face SiC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yu; Chen, Lianlian; Hilliard, Donovan

We investigated how to control the growth of vertically aligned graphene on C-face SiC by varying the processing conditions. It is found that, the growth rate scales with the annealing temperature and the graphene height is proportional to the annealing time. Temperature gradient and crystalline quality of the SiC substrates influence their vaporization. The partial vapor pressure is crucial as it can interfere with further vaporization. A growth mechanism is proposed in terms of physical vapor transport. The monolayer character of vertically aligned graphene is verified by Raman and X-ray absorption spectroscopy. With the processed samples, d 0 magnetism ismore » realized and negative magnetoresistance is observed after Cu implantation. We also prove that multiple carriers exist in vertically aligned graphene.« less

Beginning Learners' Development of Interactional Competence: Alignment Activity

ERIC Educational Resources Information Center

Tecedor, Marta

2016-01-01

This study examined the development of interactional competence (Hall, 1993; He & Young, 1998) by beginning learners of Spanish as indexed by their use of alignment moves. Discourse analysis techniques and quantitative data analysis were used to explore how 52 learners expressed alignment and changes in participation patterns in two sets of…

Measuring the scale dependence of intrinsic alignments using multiple shear estimates

NASA Astrophysics Data System (ADS)

Leonard, C. Danielle; Mandelbaum, Rachel

2018-06-01

We present a new method for measuring the scale dependence of the intrinsic alignment (IA) contamination to the galaxy-galaxy lensing signal, which takes advantage of multiple shear estimation methods applied to the same source galaxy sample. By exploiting the resulting correlation of both shape noise and cosmic variance, our method can provide an increase in the signal-to-noise of the measured IA signal as compared to methods which rely on the difference of the lensing signal from multiple photometric redshift bins. For a galaxy-galaxy lensing measurement which uses LSST sources and DESI lenses, the signal-to-noise on the IA signal from our method is predicted to improve by a factor of ˜2 relative to the method of Blazek et al. (2012), for pairs of shear estimates which yield substantially different measured IA amplitudes and highly correlated shape noise terms. We show that statistical error necessarily dominates the measurement of intrinsic alignments using our method. We also consider a physically motivated extension of the Blazek et al. (2012) method which assumes that all nearby galaxy pairs, rather than only excess pairs, are subject to IA. In this case, the signal-to-noise of the method of Blazek et al. (2012) is improved.

Application of Alignment Methodologies to Spatial Ontologies in the Hydro Domain

NASA Astrophysics Data System (ADS)

Lieberman, J. E.; Cheatham, M.; Varanka, D.

2015-12-01

Ontologies are playing an increasing role in facilitating mediation and translation between datasets representing diverse schemas, vocabularies, or knowledge communities. This role is relatively straightforward when there is one ontology comprising all relevant common concepts that can be mapped to entities in each dataset. Frequently, one common ontology has not been agreed to. Either each dataset is represented by a distinct ontology, or there are multiple candidates for commonality. Either the one most appropriate (expressive, relevant, correct) ontology must be chosen, or else concepts and relationships matched across multiple ontologies through an alignment process so that they may be used in concert to carry out mediation or other semantic operations. A resulting alignment can be effective to the extent that entities in in the ontologies represent differing terminology for comparable conceptual knowledge. In cases such as spatial ontologies, though, ontological entities may also represent disparate conceptualizations of space according to the discernment methods and application domains on which they are based. One ontology's wetland concept may overlap in space with another ontology's recharge zone or wildlife range or water feature. In order to evaluate alignment with respect to spatial ontologies, alignment has been applied to a series of ontologies pertaining to surface water that are used variously in hydrography (characterization of water features), hydrology (study of water cycling), and water quality (nutrient and contaminant transport) application domains. There is frequently a need to mediate between datasets in each domain in order to develop broader understanding of surface water systems, so there is a practical as well theoretical value in the alignment. From a domain expertise standpoint, the ontologies under consideration clearly contain some concepts that are spatially as well as conceptually identical and then others with less clear similarities in either sense. Our study serves both to determine the limits of standard methods for aligning spatial ontologies and to suggest new methods of calculating similarity axioms that take into account semantic, spatial, and cognitive criteria relevant to fitness for relevant usage scenarios.

Performance improvement in PEMFC using aligned carbon nanotubes as electrode catalyst support.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D. J.; Yang, J.; Kariuki, N.

2008-01-01

A novel membrane electrode assembly (MEA) using aligned carbon nanotubes (ACNT) as the electrocatalyst support was developed for proton exchange membrane fuel cell (PEMFC) application. A multiple-step process of preparing ACNT-PEMFC including ACNT layer growth and catalyzing, MEA fabrication, and single cell packaging is reported. Single cell polarization studies demonstrated improved fuel utilization and higher power density in comparison with the conventional, ink based MEA.

Measuring the distance between multiple sequence alignments.

PubMed

Blackburne, Benjamin P; Whelan, Simon

2012-02-15

Multiple sequence alignment (MSA) is a core method in bioinformatics. The accuracy of such alignments may influence the success of downstream analyses such as phylogenetic inference, protein structure prediction, and functional prediction. The importance of MSA has lead to the proliferation of MSA methods, with different objective functions and heuristics to search for the optimal MSA. Different methods of inferring MSAs produce different results in all but the most trivial cases. By measuring the differences between inferred alignments, we may be able to develop an understanding of how these differences (i) relate to the objective functions and heuristics used in MSA methods, and (ii) affect downstream analyses. We introduce four metrics to compare MSAs, which include the position in a sequence where a gap occurs or the location on a phylogenetic tree where an insertion or deletion (indel) event occurs. We use both real and synthetic data to explore the information given by these metrics and demonstrate how the different metrics in combination can yield more information about MSA methods and the differences between them. MetAl is a free software implementation of these metrics in Haskell. Source and binaries for Windows, Linux and Mac OS X are available from http://kumiho.smith.man.ac.uk/whelan/software/metal/.

Parallel multipoint recording of aligned and cultured neurons on micro channel array toward cellular network analysis.

PubMed

Tonomura, Wataru; Moriguchi, Hiroyuki; Jimbo, Yasuhiko; Konishi, Satoshi

2010-08-01

This paper describes an advanced Micro Channel Array (MCA) for recording electrophysiological signals of neuronal networks at multiple points simultaneously. The developed MCA is designed for neuronal network analysis which has been studied by the co-authors using the Micro Electrode Arrays (MEA) system, and employs the principles of extracellular recordings. A prerequisite for extracellular recordings with good signal-to-noise ratio is a tight contact between cells and electrodes. The MCA described herein has the following advantages. The electrodes integrated around individual micro channels are electrically isolated to enable parallel multipoint recording. Reliable clamping of a targeted cell through micro channels is expected to improve the cellular selectivity and the attachment between the cell and the electrode toward steady electrophysiological recordings. We cultured hippocampal neurons on the developed MCA. As a result, the spontaneous and evoked spike potentials could be recorded by sucking and clamping the cells at multiple points. In this paper, we describe the design and fabrication of the MCA and the successful electrophysiological recordings leading to the development of an effective cellular network analysis device.

Modeling of Field-Aligned Guided Echoes in the Plasmasphere

NASA Technical Reports Server (NTRS)

Fung, Shing F.; Green, James L.

2004-01-01

The conditions under which high frequency (f>>f(sub uh)) long-range extraordinary-mode discrete field-aligned echoes observed by the Radio Plasma Imager (RPI) on board the Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) satellite in the plasmasphere are investigated by ray tracing modeling. Field-aligned discrete echoes are most commonly observed by RPI in the plasmasphere although they are also observed over the polar cap region. The plasmasphere field-aligned echoes appearing as multiple echo traces at different virtual ranges are attributed to signals reflected successively between conjugate hemispheres that propagate along or nearly along closed geomagnetic field lines. The ray tracing simulations show that field-aligned ducts with as little as 1% density perturbations (depletions) and less than 10 wavelengths wide can guide nearly field-aligned propagating high frequency X mode waves. Effective guidance of wave at a given frequency and wave normal angle (Psi) depends on the cross-field density scale of the duct, such that ducts with stronger density depletions need to be wider in order to maintain the same gradient of refractive index across the magnetic field. While signal guidance by field aligned density gradient without ducting is possible only over the polar region, conjugate field-aligned echoes that have traversed through the equatorial region are most likely guided by ducting.

HubAlign: an accurate and efficient method for global alignment of protein-protein interaction networks.

PubMed

Hashemifar, Somaye; Xu, Jinbo

2014-09-01

High-throughput experimental techniques have produced a large amount of protein-protein interaction (PPI) data. The study of PPI networks, such as comparative analysis, shall benefit the understanding of life process and diseases at the molecular level. One way of comparative analysis is to align PPI networks to identify conserved or species-specific subnetwork motifs. A few methods have been developed for global PPI network alignment, but it still remains challenging in terms of both accuracy and efficiency. This paper presents a novel global network alignment algorithm, denoted as HubAlign, that makes use of both network topology and sequence homology information, based upon the observation that topologically important proteins in a PPI network usually are much more conserved and thus, more likely to be aligned. HubAlign uses a minimum-degree heuristic algorithm to estimate the topological and functional importance of a protein from the global network topology information. Then HubAlign aligns topologically important proteins first and gradually extends the alignment to the whole network. Extensive tests indicate that HubAlign greatly outperforms several popular methods in terms of both accuracy and efficiency, especially in detecting functionally similar proteins. HubAlign is available freely for non-commercial purposes at http://ttic.uchicago.edu/∼hashemifar/software/HubAlign.zip. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Multi-species Identification of Polymorphic Peptide Variants via Propagation in Spectral Networks*

PubMed Central

Bandeira, Nuno

2016-01-01

Peptide and protein identification remains challenging in organisms with poorly annotated or rapidly evolving genomes, as are commonly encountered in environmental or biofuels research. Such limitations render tandem mass spectrometry (MS/MS) database search algorithms ineffective as they lack corresponding sequences required for peptide-spectrum matching. We address this challenge with the spectral networks approach to (1) match spectra of orthologous peptides across multiple related species and then (2) propagate peptide annotations from identified to unidentified spectra. We here present algorithms to assess the statistical significance of spectral alignments (Align-GF), reduce the impurity in spectral networks, and accurately estimate the error rate in propagated identifications. Analyzing three related Cyanothece species, a model organism for biohydrogen production, spectral networks identified peptides from highly divergent sequences from networks with dozens of variant peptides, including thousands of peptides in species lacking a sequenced genome. Our analysis further detected the presence of many novel putative peptides even in genomically characterized species, thus suggesting the possibility of gaps in our understanding of their proteomic and genomic expression. A web-based pipeline for spectral networks analysis is available at http://proteomics.ucsd.edu/software. PMID:27609420

phylo-node: A molecular phylogenetic toolkit using Node.js.

PubMed

O'Halloran, Damien M

2017-01-01

Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.

Experimental assessment and analysis of super-resolution in fluorescence microscopy based on multiple-point spread function fitting of spectrally demultiplexed images

NASA Astrophysics Data System (ADS)

Nishimura, Takahiro; Kimura, Hitoshi; Ogura, Yusuke; Tanida, Jun

2018-06-01

This paper presents an experimental assessment and analysis of super-resolution microscopy based on multiple-point spread function fitting of spectrally demultiplexed images using a designed DNA structure as a test target. For the purpose, a DNA structure was designed to have binding sites at a certain interval that is smaller than the diffraction limit. The structure was labeled with several types of quantum dots (QDs) to acquire their spatial information as spectrally encoded images. The obtained images are analyzed with a point spread function multifitting algorithm to determine the QD locations that indicate the binding site positions. The experimental results show that the labeled locations can be observed beyond the diffraction-limited resolution using three-colored fluorescence images that were obtained with a confocal fluorescence microscope. Numerical simulations show that labeling with eight types of QDs enables the positions aligned at 27.2-nm pitches on the DNA structure to be resolved with high accuracy.

How To Build an Integrated Neighborhood Approach to Support Community-Dwelling Older People?

PubMed Central

Cramm, Jane Murray; Nieboer, Anna Petra

2016-01-01

Background: Although the need for integrated neighborhood approaches (INAs) is widely recognized, we lack insight into strategies like INA. We describe diverse Dutch INA partners’ experiences to provide integrated person- and population-centered support to community-dwelling older people using an adapted version of Valentijn and colleagues’ integrated care model. Our main objective was to explore the experiences with INA participation. We sought to increase our understanding of the challenges facing these partners and identify factors facilitating and inhibiting integration within and among multiple levels. Methods: Twenty-one interviews with INA partners (including local health and social care organizations, older people, municipal officers, and a health insurer) were conducted and subjected to latent content analysis. Results: This study showed that integrated care and support provision through an INA is a complex, dynamic process requiring multilevel alignment of activities. The INA achieved integration at the personal, service, and professional levels only occasionally. Micro-level bottom-up initiatives were not aligned with top-down incentives, forcing community workers to establish integration despite rather than because of meso- and macro-level contexts. Conclusions: Top-down incentives should be better aligned with bottom-up initiatives. This study further demonstrated the importance of community-level engagement in integrated care and support provision. PMID:27616960

Delivering on the Promise of CLER: A Patient Safety Rotation That Aligns Resident Education With Hospital Processes.

PubMed

Patel, Ekta; Muthusamy, Veena; Young, John Q

2018-06-01

Residency programs must provide training in patient safety. Yet, significant gaps exist among published patient safety curricula. The authors developed a rotation designed to be scalable to an entire residency, built on sound pedagogy, aligned with hospital safety processes, and effective in improving educational outcomes. From July 2015 to May 2017, each second-year resident completed the two-week rotation. Residents engaged the foundational science asynchronously via multiple modalities and then practiced applying key concepts during a mock root cause analysis. Next, each resident performed a special review of an actual adverse patient event and presented findings to the hospital's Special Review Committee (SRC). Multiple educational outcomes were assessed, including resident satisfaction and attitudes (postrotation survey), changes in knowledge via pre- and posttest, quality of the residents' written safety analyses and oral presentations (per survey of SRC members), and organizational changes that resulted from the residents' reviews. Twenty-two residents completed the rotation. Most components were rated favorably; 80% (12/15 respondents) indicated interest in future patient safety work. Knowledge improved by 44.3% (P < .0001; pretest mean 23.7, posttest mean 34.2). Compared to faculty, SRC members rated the quality of residents' written reviews as superior and the quality of the rated oral presentations as either comparable or superior. The reviews identified a variety of safety vulnerabilities and led to multiple corrective actions. The authors will evaluate the curriculum in a controlled trial with better measures of change in behavior. Further tests of the curriculum's scalability to other contexts are needed.

Aptaligner: automated software for aligning pseudorandom DNA X-aptamers from next-generation sequencing data.

PubMed

Lu, Emily; Elizondo-Riojas, Miguel-Angel; Chang, Jeffrey T; Volk, David E

2014-06-10

Next-generation sequencing results from bead-based aptamer libraries have demonstrated that traditional DNA/RNA alignment software is insufficient. This is particularly true for X-aptamers containing specialty bases (W, X, Y, Z, ...) that are identified by special encoding. Thus, we sought an automated program that uses the inherent design scheme of bead-based X-aptamers to create a hypothetical reference library and Markov modeling techniques to provide improved alignments. Aptaligner provides this feature as well as length error and noise level cutoff features, is parallelized to run on multiple central processing units (cores), and sorts sequences from a single chip into projects and subprojects.

Thermal resilient multiple jaw braze fixture

DOEpatents

Ney, Robert; Perrone, Alex J.

1995-07-11

A braze fixture has side walls forming a cavity with an opening to receive a stack of parts to be brazed. Sidewalls of the housing have a plurality of bearing receiving openings into which bearing rods or jaws are inserted to align the stacked elements of the workpiece. The housing can also have view ports to allow a visual check of the alignment. Straps or wires around the fixture are selected to have thermal characteristics similar to the thermal characteristics of the workpiece undergoing brazing. The straps or wires make physical contact with the bearing rods thereby causing bearing rods to maintain the workpiece in proper alignment throughout the entire brazing cycle.

ScanIndel: a hybrid framework for indel detection via gapped alignment, split reads and de novo assembly.

PubMed

Yang, Rendong; Nelson, Andrew C; Henzler, Christine; Thyagarajan, Bharat; Silverstein, Kevin A T

2015-12-07

Comprehensive identification of insertions/deletions (indels) across the full size spectrum from second generation sequencing is challenging due to the relatively short read length inherent in the technology. Different indel calling methods exist but are limited in detection to specific sizes with varying accuracy and resolution. We present ScanIndel, an integrated framework for detecting indels with multiple heuristics including gapped alignment, split reads and de novo assembly. Using simulation data, we demonstrate ScanIndel's superior sensitivity and specificity relative to several state-of-the-art indel callers across various coverage levels and indel sizes. ScanIndel yields higher predictive accuracy with lower computational cost compared with existing tools for both targeted resequencing data from tumor specimens and high coverage whole-genome sequencing data from the human NIST standard NA12878. Thus, we anticipate ScanIndel will improve indel analysis in both clinical and research settings. ScanIndel is implemented in Python, and is freely available for academic use at https://github.com/cauyrd/ScanIndel.

Finding similar nucleotide sequences using network BLAST searches.

PubMed

Ladunga, Istvan

2009-06-01

The Basic Local Alignment Search Tool (BLAST) is a keystone of bioinformatics due to its performance and user-friendliness. Beginner and intermediate users will learn how to design and submit blastn and Megablast searches on the Web pages at the National Center for Biotechnology Information. We map nucleic acid sequences to genomes, find identical or similar mRNA, expressed sequence tag, and noncoding RNA sequences, and run Megablast searches, which are much faster than blastn. Understanding results is assisted by taxonomy reports, genomic views, and multiple alignments. We interpret expected frequency thresholds, biological significance, and statistical significance. Weak hits provide no evidence, but hints for further analyses. We find genes that may code for homologous proteins by translated BLAST. We reduce false positives by filtering out low-complexity regions. Parsed BLAST results can be integrated into analysis pipelines. Links in the output connect to Entrez, PUBMED, structural, sequence, interaction, and expression databases. This facilitates integration with a wide spectrum of biological knowledge.

Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events.

PubMed

Ramirez-Villegas, Juan F; Logothetis, Nikos K; Besserve, Michel

2015-11-17

Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.

Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events

PubMed Central

Ramirez-Villegas, Juan F.; Logothetis, Nikos K.; Besserve, Michel

2015-01-01

Sharp-wave–ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R–triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions. PMID:26540729

Alignment and Integration of Lightweight Mirror Segments

NASA Technical Reports Server (NTRS)

Evans, Tyler; Biskach, Michael; Mazzarella, Jim; McClelland, Ryan; Saha, Timo; Zhang, Will; Chan, Kai-Wing

2011-01-01

The optics for the International X-Ray Observatory (IXO) require alignment and integration of about fourteen thousand thin mirror segments to achieve the mission goal of 3.0 square meters of effective area at 1.25 keV with an angular resolution of five arc-seconds. These mirror segments are 0.4 mm thick, and 200 to 400 mm in size, which makes it difficult not to impart distortion at the sub-arc-second level. This paper outlines the precise alignment, permanent bonding, and verification testing techniques developed at NASA's Goddard Space Flight Center (GSFC). Improvements in alignment include new hardware and automation software. Improvements in bonding include two module new simulators to bond mirrors into, a glass housing for proving single pair bonding, and a Kovar module for bonding multiple pairs of mirrors. Three separate bonding trials were x-ray tested producing results meeting the requirement of sub ten arc-second alignment. This paper will highlight these recent advances in alignment, testing, and bonding techniques and the exciting developments in thin x-ray optic technology development.

Flexible and Lightweight Pressure Sensor Based on Carbon Nanotube/Thermoplastic Polyurethane-Aligned Conductive Foam with Superior Compressibility and Stability.

PubMed

Huang, Wenju; Dai, Kun; Zhai, Yue; Liu, Hu; Zhan, Pengfei; Gao, Jiachen; Zheng, Guoqiang; Liu, Chuntai; Shen, Changyu

2017-12-06

Flexible and lightweight carbon nanotube (CNT)/thermoplastic polyurethane (TPU) conductive foam with a novel aligned porous structure was fabricated. The density of the aligned porous material was as low as 0.123 g·cm -3 . Homogeneous dispersion of CNTs was achieved through the skeleton of the foam, and an ultralow percolation threshold of 0.0023 vol % was obtained. Compared with the disordered foam, mechanical properties of the aligned foam were enhanced and the piezoresistive stability of the flexible foam was improved significantly. The compression strength of the aligned TPU foam increases by 30.7% at the strain of 50%, and the stress of the aligned foam is 22 times that of the disordered foam at the strain of 90%. Importantly, the resistance variation of the aligned foam shows a fascinating linear characteristic under the applied strain until 77%, which would benefit the application of the foam as a desired pressure sensor. During multiple cyclic compression-release measurements, the aligned conductive CNT/TPU foam represents excellent reversibility and reproducibility in terms of resistance. This nice capability benefits from the aligned porous structure composed of ladderlike cells along the orientation direction. Simultaneously, the human motion detections, such as walk, jump, squat, etc. were demonstrated by using our flexible pressure sensor. Because of the lightweight, flexibility, high compressibility, excellent reversibility, and reproducibility of the conductive aligned foam, the present study is capable of providing new insights into the fabrication of a high-performance pressure sensor.

Organic light emitting device having multiple separate emissive layers

DOEpatents

Forrest, Stephen R [Ann Arbor, MI

2012-03-27

An organic light emitting device having multiple separate emissive layers is provided. Each emissive layer may define an exciton formation region, allowing exciton formation to occur across the entire emissive region. By aligning the energy levels of each emissive layer with the adjacent emissive layers, exciton formation in each layer may be improved. Devices incorporating multiple emissive layers with multiple exciton formation regions may exhibit improved performance, including internal quantum efficiencies of up to 100%.

Sagittal Vertical Axias, Spinosacral Angle, Spinopelvic Angle, and T1 Pelvic Angle: Which Parameters May Effectively Predict the Quality of Life in Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?

PubMed

Zhang, Yun-Peng; Qian, Bang-Ping; Qiu, Yong; Qu, Zhe; Mao, Sai-Hu; Jiang, Jun; Zhu, Ze-Zhang

2017-08-01

This is a retrospective study. To identify the relationship between global sagittal alignment and health-related quality of life (HRQoL) in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. Little data are available on correlation between global sagittal alignment and HRQoL in AS. A total of 107 AS patients were included in this study. The radiographic parameters were measured on lateral radiographs of the whole spine, including sagittal vertical axias (SVA), spinosacral angle (SSA), spinopelvic angle (SPA), and T1 pelvic angle (TPA). HRQoL was assessed using the oswestry disability index questionnaire, the bath ankylosing spondylitis disease activity index, the bath ankylosing spondylitis functional index, and short form-36 questionnaire. The patients were divided into 2 groups: group A (n=76, global kyphosis≤70 degrees), group B (n=31, global kyphosis>70 degrees). Statistical analysis was performed to identify significant differences between these 2 groups. In addition, correlation analysis and multiple regression analysis between radiologic parameters and clinical questionnaires were conducted. With respect to SVA, SSA, SPA, TPA, and HRQoL scores, significant differences were observed between 2 groups (P<0.05). Also, SVA, SSA, SPA, and TPA were significantly related to HRQoL. Multiple regression analysis revealed that SVA, SSA, SPA, and TPA were significant parameters in the prediction of HRQoL in AS patients with thoracolumbar kyphosis. Of note, HRQoL related much more to SSA and SPA than SVA and TPA. AS patients with moderate and severe deformity were demonstrated to be significantly different in terms of SVA, SSA, SPA, TPA, and HRQoL. Moreover, SVA, SSA, SPA, and TPA correlated with HRQoL significantly. In particular, SSA and SPA could better predict HRQoL than SVA and TPA in AS patients with thoracolumbar kyphosis.

The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics

PubMed Central

2012-01-01

Background Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis. Results To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively. Conclusions We describe an analysis pipeline for the efficient handling and analysis of time-series microscopy data that enhances productivity and facilitates the phenotypic characterization of genetic perturbations. Our methodology can easily be scaled up for genome-wide genetic screens using readily available resources for RNAi based gene silencing in Drosophila and other animal models. PMID:23282138

REFGEN and TREENAMER: Automated Sequence Data Handling for Phylogenetic Analysis in the Genomic Era

PubMed Central

Leonard, Guy; Stevens, Jamie R.; Richards, Thomas A.

2009-01-01

The phylogenetic analysis of nucleotide sequences and increasingly that of amino acid sequences is used to address a number of biological questions. Access to extensive datasets, including numerous genome projects, means that standard phylogenetic analyses can include many hundreds of sequences. Unfortunately, most phylogenetic analysis programs do not tolerate the sequence naming conventions of genome databases. Managing large numbers of sequences and standardizing sequence labels for use in phylogenetic analysis programs can be a time consuming and laborious task. Here we report the availability of an online resource for the management of gene sequences recovered from public access genome databases such as GenBank. These web utilities include the facility for renaming every sequence in a FASTA alignment file, with each sequence label derived from a user-defined combination of the species name and/or database accession number. This facility enables the user to keep track of the branching order of the sequences/taxa during multiple tree calculations and re-optimisations. Post phylogenetic analysis, these webpages can then be used to rename every label in the subsequent tree files (with a user-defined combination of species name and/or database accession number). Together these programs drastically reduce the time required for managing sequence alignments and labelling phylogenetic figures. Additional features of our platform include the automatic removal of identical accession numbers (recorded in the report file) and generation of species and accession number lists for use in supplementary materials or figure legends. PMID:19812722

Fabrication, Testing, Coating and Alignment of Fast Segmented Optics

DTIC Science & Technology

2006-05-25

mirror segment, a 100 mm thick Zerodur mirror blank was purchased from Schott. Figure 2 shows the segment and its support for polishing and testing in...Polishing large off-axis segments of fast primary mirrors 2. Testing large segments in an off-axis geometry 3. Alignment of multiple segments of a large... mirror 4. Coatings that reflect high-intensity light without distorting the substrate These technologies are critical because of several unique

Optical design of the National Ignition Facility main laser and switchyard/target area beam transport systems

NASA Astrophysics Data System (ADS)

Miller, John L.; English, R. Edward, Jr.; Korniski, Ronald J.; Rodgers, J. Michael

1999-07-01

The optical design of the main laser and transport mirror sections of the National Ignition Facility are described. For the main laser the configuration, layout constraints, multiple beam arrangement, pinhole layout and beam paths, clear aperture budget, ray trace models, alignment constraints, lens designs, wavefront performance, and pupil aberrations are discussed. For the transport mirror system the layout, alignment controls and clear aperture budget are described.

Comparative Analysis of Mass Spectral Similarity Measures on Peak Alignment for Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry

PubMed Central

2013-01-01

Peak alignment is a critical procedure in mass spectrometry-based biomarker discovery in metabolomics. One of peak alignment approaches to comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) data is peak matching-based alignment. A key to the peak matching-based alignment is the calculation of mass spectral similarity scores. Various mass spectral similarity measures have been developed mainly for compound identification, but the effect of these spectral similarity measures on the performance of peak matching-based alignment still remains unknown. Therefore, we selected five mass spectral similarity measures, cosine correlation, Pearson's correlation, Spearman's correlation, partial correlation, and part correlation, and examined their effects on peak alignment using two sets of experimental GC×GC-MS data. The results show that the spectral similarity measure does not affect the alignment accuracy significantly in analysis of data from less complex samples, while the partial correlation performs much better than other spectral similarity measures when analyzing experimental data acquired from complex biological samples. PMID:24151524

Ultrahigh density alignment of carbon nanotube arrays by dielectrophoresis.

PubMed

Shekhar, Shashank; Stokes, Paul; Khondaker, Saiful I

2011-03-22

We report ultrahigh density assembly of aligned single-walled carbon nanotube (SWNT) two-dimensional arrays via AC dielectrophoresis using high-quality surfactant-free and stable SWNT solutions. After optimization of frequency and trapping time, we can reproducibly control the linear density of the SWNT between prefabricated electrodes from 0.5 SWNT/μm to more than 30 SWNT/μm by tuning the concentration of the nanotubes in the solution. Our maximum density of 30 SWNT/μm is the highest for aligned arrays via any solution processing technique reported so far. Further increase of SWNT concentration results in a dense array with multiple layers. We discuss how the orientation and density of the nanotubes vary with concentrations and channel lengths. Electrical measurement data show that the densely packed aligned arrays have low sheet resistances. Selective removal of metallic SWNTs via controlled electrical breakdown produced field-effect transistors with high current on-off ratio. Ultrahigh density alignment reported here will have important implications in fabricating high-quality devices for digital and analog electronics.

Passively aligned multichannel fiber-pigtailing of planar integrated optical waveguides

NASA Astrophysics Data System (ADS)

Kremmel, Johannes; Lamprecht, Tobias; Crameri, Nino; Michler, Markus

2017-02-01

A silicon device to simplify the coupling of multiple single-mode fibers to embedded single-mode waveguides has been developed. The silicon device features alignment structures that enable a passive alignment of fibers to integrated waveguides. For passive alignment, precisely machined V-grooves on a silicon device are used and the planar lightwave circuit board features high-precision structures acting as a mechanical stop. The approach has been tested for up to eight fiber-to-waveguide connections. The alignment approach, the design, and the fabrication of the silicon device as well as the assembly process are presented. The characterization of the fiber-to-waveguide link reveals total coupling losses of (0.45±0.20 dB) per coupling interface, which is significantly lower than the values reported in earlier works. Subsequent climate tests reveal that the coupling losses remain stable during thermal cycling but increases significantly during an 85°C/85 Rh-test. All applied fabrication and bonding steps have been performed using standard MOEMS fabrication and packaging processes.

Adaptive Local Realignment of Protein Sequences.

PubMed

DeBlasio, Dan; Kececioglu, John

2018-06-11

While mutation rates can vary markedly over the residues of a protein, multiple sequence alignment tools typically use the same values for their scoring-function parameters across a protein's entire length. We present a new approach, called adaptive local realignment, that in contrast automatically adapts to the diversity of mutation rates along protein sequences. This builds upon a recent technique known as parameter advising, which finds global parameter settings for an aligner, to now adaptively find local settings. Our approach in essence identifies local regions with low estimated accuracy, constructs a set of candidate realignments using a carefully-chosen collection of parameter settings, and replaces the region if a realignment has higher estimated accuracy. This new method of local parameter advising, when combined with prior methods for global advising, boosts alignment accuracy as much as 26% over the best default setting on hard-to-align protein benchmarks, and by 6.4% over global advising alone. Adaptive local realignment has been implemented within the Opal aligner using the Facet accuracy estimator.

Comparative Evaluation of Preprocessing Freeware on Chromatography/Mass Spectrometry Data for Signature Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coble, Jamie B.; Fraga, Carlos G.

2014-07-07

Preprocessing software is crucial for the discovery of chemical signatures in metabolomics, chemical forensics, and other signature-focused disciplines that involve analyzing large data sets from chemical instruments. Here, four freely available and published preprocessing tools known as metAlign, MZmine, SpectConnect, and XCMS were evaluated for impurity profiling using nominal mass GC/MS data and accurate mass LC/MS data. Both data sets were previously collected from the analysis of replicate samples from multiple stocks of a nerve-agent precursor. Each of the four tools had their parameters set for the untargeted detection of chromatographic peaks from impurities present in the stocks. The peakmore » table generated by each preprocessing tool was analyzed to determine the number of impurity components detected in all replicate samples per stock. A cumulative set of impurity components was then generated using all available peak tables and used as a reference to calculate the percent of component detections for each tool, in which 100% indicated the detection of every component. For the nominal mass GC/MS data, metAlign performed the best followed by MZmine, SpectConnect, and XCMS with detection percentages of 83, 60, 47, and 42%, respectively. For the accurate mass LC/MS data, the order was metAlign, XCMS, and MZmine with detection percentages of 80, 45, and 35%, respectively. SpectConnect did not function for the accurate mass LC/MS data. Larger detection percentages were obtained by combining the top performer with at least one of the other tools such as 96% by combining metAlign with MZmine for the GC/MS data and 93% by combining metAlign with XCMS for the LC/MS data. In terms of quantitative performance, the reported peak intensities had average absolute biases of 41, 4.4, 1.3 and 1.3% for SpectConnect, metAlign, XCMS, and MZmine, respectively, for the GC/MS data. For the LC/MS data, the average absolute biases were 22, 4.5, and 3.1% for metAlign, MZmine, and XCMS, respectively. In summary, metAlign performed the best in terms of peak discovery; however, more than one preprocessing tool should be considered to avoid missing potential chemical signatures.« less

Practical, computer-aided registration of multiple, three-dimensional, magnetic-resonance observations of the human brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diegert, C.; Sanders, J.A.; Orrison, W.W. Jr.

1992-12-31

Researchers working with MR observations generally agree that far more information is available in a volume (3D) observation than is considered for diagnosis. The key to the new alignment method is in basing it on available information on surfaces. Using the skin surface is effective a robust algorithm can reliably extract this surface from almost any scan of the head, and a human operator`s exquisite sensitivity to facial features is allows him to manually align skin surfaces with precision. Following the definitions, we report on a preliminary experiment where we align three MR observations taken during a single MR examination,more » each weighting arterial, venous, and tissue features. When accurately aligned, a neurosurgeon can use these features as anatomical landmarks for planning and executing interventional procedures.« less

Simulator for beam-based LHC collimator alignment

NASA Astrophysics Data System (ADS)

Valentino, Gianluca; Aßmann, Ralph; Redaelli, Stefano; Sammut, Nicholas

2014-02-01

In the CERN Large Hadron Collider, collimators need to be set up to form a multistage hierarchy to ensure efficient multiturn cleaning of halo particles. Automatic algorithms were introduced during the first run to reduce the beam time required for beam-based setup, improve the alignment accuracy, and reduce the risk of human errors. Simulating the alignment procedure would allow for off-line tests of alignment policies and algorithms. A simulator was developed based on a diffusion beam model to generate the characteristic beam loss signal spike and decay produced when a collimator jaw touches the beam, which is observed in a beam loss monitor (BLM). Empirical models derived from the available measurement data are used to simulate the steady-state beam loss and crosstalk between multiple BLMs. The simulator design is presented, together with simulation results and comparison to measurement data.

Node fingerprinting: an efficient heuristic for aligning biological networks.

PubMed

Radu, Alex; Charleston, Michael

2014-10-01

With the continuing increase in availability of biological data and improvements to biological models, biological network analysis has become a promising area of research. An emerging technique for the analysis of biological networks is through network alignment. Network alignment has been used to calculate genetic distance, similarities between regulatory structures, and the effect of external forces on gene expression, and to depict conditional activity of expression modules in cancer. Network alignment is algorithmically complex, and therefore we must rely on heuristics, ideally as efficient and accurate as possible. The majority of current techniques for network alignment rely on precomputed information, such as with protein sequence alignment, or on tunable network alignment parameters, which may introduce an increased computational overhead. Our presented algorithm, which we call Node Fingerprinting (NF), is appropriate for performing global pairwise network alignment without precomputation or tuning, can be fully parallelized, and is able to quickly compute an accurate alignment between two biological networks. It has performed as well as or better than existing algorithms on biological and simulated data, and with fewer computational resources. The algorithmic validation performed demonstrates the low computational resource requirements of NF.

Optical Analysis And Alignment Applications Using The Infrared Smartt Interferometer

NASA Astrophysics Data System (ADS)

Viswanathan, V. K.; Bolen, P. D.; Liberman, I.; Seery, B. D.

1981-12-01

The possiblility of using the infrared Smartt interferometer for optical analysis and alignment of infrared laser systems has been discussed previously. In this paper, optical analysis of the Gigawatt Test Facility at Los Alamos, as well as a deformable mirror manufactured by Rocketdyne, are discussed as examples of the technique. The possibility of optically characterizing, as well as aligning, pulsed high energy laser systems like Helios and Antares is discussed in some detail.

Optical analysis and alignment applications using the infrared Smartt interferometer

NASA Astrophysics Data System (ADS)

Viswanathan, V. K.; Bolen, P. D.; Liberman, I.; Seery, B. D.

The possibility of using the infrared Smartt interferometer for optical analysis and alignment of infrared laser systems has been discussed previously. In this paper, optical analysis of the Gigawatt Test Facility at Los Alamos, as well as a deformable mirror manufactured by Rocketdyne, are discussed as examples of the technique. The possibility of optically characterizing, as well as aligning, pulsed high energy laser systems like Helios and Antares is discussed in some detail.

Rapid detection, classification and accurate alignment of up to a million or more related protein sequences.

PubMed

Neuwald, Andrew F

2009-08-01

The patterns of sequence similarity and divergence present within functionally diverse, evolutionarily related proteins contain implicit information about corresponding biochemical similarities and differences. A first step toward accessing such information is to statistically analyze these patterns, which, in turn, requires that one first identify and accurately align a very large set of protein sequences. Ideally, the set should include many distantly related, functionally divergent subgroups. Because it is extremely difficult, if not impossible for fully automated methods to align such sequences correctly, researchers often resort to manual curation based on detailed structural and biochemical information. However, multiply-aligning vast numbers of sequences in this way is clearly impractical. This problem is addressed using Multiply-Aligned Profiles for Global Alignment of Protein Sequences (MAPGAPS). The MAPGAPS program uses a set of multiply-aligned profiles both as a query to detect and classify related sequences and as a template to multiply-align the sequences. It relies on Karlin-Altschul statistics for sensitivity and on PSI-BLAST (and other) heuristics for speed. Using as input a carefully curated multiple-profile alignment for P-loop GTPases, MAPGAPS correctly aligned weakly conserved sequence motifs within 33 distantly related GTPases of known structure. By comparison, the sequence- and structurally based alignment methods hmmalign and PROMALS3D misaligned at least 11 and 23 of these regions, respectively. When applied to a dataset of 65 million protein sequences, MAPGAPS identified, classified and aligned (with comparable accuracy) nearly half a million putative P-loop GTPase sequences. A C++ implementation of MAPGAPS is available at http://mapgaps.igs.umaryland.edu. Supplementary data are available at Bioinformatics online.

Effect of alignment changes on sagittal and coronal socket reaction moment interactions in transtibial prostheses.

PubMed

Kobayashi, Toshiki; Orendurff, Michael S; Zhang, Ming; Boone, David A

2013-04-26

Alignment is important for comfortable and stable gait of lower-limb prosthesis users. The magnitude of socket reaction moments in the multiple planes acting simultaneously upon the residual limb may be related to perception of comfort in individuals using prostheses through socket interface pressures. The aim of this study was to investigate the effect of prosthetic alignment changes on sagittal and coronal socket reaction moment interactions (moment-moment curves) and to characterize the curves in 11 individuals with transtibial amputation using novel moment-moment interaction parameters measured by plotting sagittal socket reaction moments versus coronal ones under various alignment conditions. A custom instrumented prosthesis alignment component was used to measure socket reaction moments during walking. Prosthetic alignment was tuned to a nominally aligned condition by a prosthetist, and from this position, angular (3° and 6° of flexion, extension, abduction or adduction of the socket) and translational (5mm and 10mm of anterior, posterior, medial or lateral translation of the socket) alignment changes were performed in either the sagittal or the coronal plane in a randomized manner. A total of 17 alignment conditions were tested. Coronal angulation and translation alignment changes demonstrated similar consistent changes in the moment-moment curves. Sagittal alignment changes demonstrated more complex changes compared to the coronal alignment changes. Effect of sagittal angulations and translations on the moment-moment curves was different during 2nd rocker (mid-stance) with extension malalignment appearing to cause medio-lateral instability. Presentation of coronal and sagittal socket reaction moment interactions may provide useful visual information for prosthetists to understand the biomechanical effects of malalignment of transtibial prostheses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spontaneous Magnetic Alignment by Yearling Snapping Turtles: Rapid Association of Radio Frequency Dependent Pattern of Magnetic Input with Novel Surroundings

PubMed Central

Landler, Lukas; Painter, Michael S.; Youmans, Paul W.; Hopkins, William A.; Phillips, John B.

2015-01-01

We investigated spontaneous magnetic alignment (SMA) by juvenile snapping turtles using exposure to low-level radio frequency (RF) fields at the Larmor frequency to help characterize the underlying sensory mechanism. Turtles, first introduced to the testing environment without the presence of RF aligned consistently towards magnetic north when subsequent magnetic testing conditions were also free of RF (‘RF off → RF off’), but were disoriented when subsequently exposed to RF (‘RF off → RF on’). In contrast, animals initially introduced to the testing environment with RF present were disoriented when tested without RF (‘RF on → RF off’), but aligned towards magnetic south when tested with RF (‘RF on → RF on’). Sensitivity of the SMA response of yearling turtles to RF is consistent with the involvement of a radical pair mechanism. Furthermore, the effect of RF appears to result from a change in the pattern of magnetic input, rather than elimination of magnetic input altogether, as proposed to explain similar effects in other systems/organisms. The findings show that turtles first exposed to a novel environment form a lasting association between the pattern of magnetic input and their surroundings. However, under natural conditions turtles would never experience a change in the pattern of magnetic input. Therefore, if turtles form a similar association of magnetic cues with the surroundings each time they encounter unfamiliar habitat, as seems likely, the same pattern of magnetic input would be associated with multiple sites/localities. This would be expected from a sensory input that functions as a global reference frame, helping to place multiple locales (i.e., multiple local landmark arrays) into register to form a global map of familiar space. PMID:25978736

Spontaneous magnetic alignment by yearling snapping turtles: rapid association of radio frequency dependent pattern of magnetic input with novel surroundings.

PubMed

Landler, Lukas; Painter, Michael S; Youmans, Paul W; Hopkins, William A; Phillips, John B

2015-01-01

We investigated spontaneous magnetic alignment (SMA) by juvenile snapping turtles using exposure to low-level radio frequency (RF) fields at the Larmor frequency to help characterize the underlying sensory mechanism. Turtles, first introduced to the testing environment without the presence of RF aligned consistently towards magnetic north when subsequent magnetic testing conditions were also free of RF ('RF off → RF off'), but were disoriented when subsequently exposed to RF ('RF off → RF on'). In contrast, animals initially introduced to the testing environment with RF present were disoriented when tested without RF ('RF on → RF off'), but aligned towards magnetic south when tested with RF ('RF on → RF on'). Sensitivity of the SMA response of yearling turtles to RF is consistent with the involvement of a radical pair mechanism. Furthermore, the effect of RF appears to result from a change in the pattern of magnetic input, rather than elimination of magnetic input altogether, as proposed to explain similar effects in other systems/organisms. The findings show that turtles first exposed to a novel environment form a lasting association between the pattern of magnetic input and their surroundings. However, under natural conditions turtles would never experience a change in the pattern of magnetic input. Therefore, if turtles form a similar association of magnetic cues with the surroundings each time they encounter unfamiliar habitat, as seems likely, the same pattern of magnetic input would be associated with multiple sites/localities. This would be expected from a sensory input that functions as a global reference frame, helping to place multiple locales (i.e., multiple local landmark arrays) into register to form a global map of familiar space.

MATHEMATICAL ANALYSIS OF STEADY-STATE SOLUTIONS IN COMPARTMENT AND CONTINUUM MODELS OF CELL POLARIZATION

PubMed Central

ZHENG, ZHENZHEN; CHOU, CHING-SHAN; YI, TAU-MU; NIE, QING

2013-01-01

Cell polarization, in which substances previously uniformly distributed become asymmetric due to external or/and internal stimulation, is a fundamental process underlying cell mobility, cell division, and other polarized functions. The yeast cell S. cerevisiae has been a model system to study cell polarization. During mating, yeast cells sense shallow external spatial gradients and respond by creating steeper internal gradients of protein aligned with the external cue. The complex spatial dynamics during yeast mating polarization consists of positive feedback, degradation, global negative feedback control, and cooperative effects in protein synthesis. Understanding such complex regulations and interactions is critical to studying many important characteristics in cell polarization including signal amplification, tracking dynamic signals, and potential trade-off between achieving both objectives in a robust fashion. In this paper, we study some of these questions by analyzing several models with different spatial complexity: two compartments, three compartments, and continuum in space. The step-wise approach allows detailed characterization of properties of the steady state of the system, providing more insights for biological regulations during cell polarization. For cases without membrane diffusion, our study reveals that increasing the number of spatial compartments results in an increase in the number of steady-state solutions, in particular, the number of stable steady-state solutions, with the continuum models possessing infinitely many steady-state solutions. Through both analysis and simulations, we find that stronger positive feedback, reduced diffusion, and a shallower ligand gradient all result in more steady-state solutions, although most of these are not optimally aligned with the gradient. We explore in the different settings the relationship between the number of steady-state solutions and the extent and accuracy of the polarization. Taken together these results furnish a detailed description of the factors that influence the tradeoff between a single correctly aligned but poorly polarized stable steady-state solution versus multiple more highly polarized stable steady-state solutions that may be incorrectly aligned with the external gradient. PMID:21936604

Imageless navigation system does not improve component rotational alignment in total knee arthroplasty.

PubMed

Cheng, Tao; Zhang, Guoyou; Zhang, Xianlong

2011-12-01

The aim of computer-assisted surgery is to improve accuracy and limit the range of surgical variability. However, a worldwide debate exists regarding the importance and usefulness of computer-assisted navigation for total knee arthroplasty (TKA). The main purpose of this study is to summarize and compare the radiographic outcomes of TKA performed using imageless computer-assisted navigation compared with conventional techniques. An electronic search of PubMed, EMBASE, Web of Science, and Cochrane library databases was made, in addition to manual search of major orthopedic journals. A meta-analysis of 29 quasi-randomized/randomized controlled trials (quasi-RCTs/RCTs) and 11 prospective comparative studies was conducted through a random effects model. Additional a priori sources of clinical heterogeneity were evaluated by subgroup analysis with regard to radiographic methods. When the outlier cut-off value of lower limb axis was defined as ±2° or ±3° from the neutral, the postoperative full-length radiographs demonstrated that the risk ratio was 0.54 or 0.39, respectively, which were in favor of the navigated group. When the cut-off value used for the alignment in the coronal and sagittal plane was 2° or 3°, imageless navigation significantly reduced the outlier rate of the femoral and tibial components compared with the conventional group. Notably, computed tomography scans demonstrated no statistically significant differences between the two groups regarding the outliers in the rotational alignment of the femoral and tibial components; however, there was strong statistical heterogeneity. Our results indicated that imageless computer-assisted navigation systems improve lower limb axis and component orientation in the coronal and sagittal planes, but not the rotational alignment in TKA. Further multiple-center clinical trials with long-term follow-up are needed to determine differences in the clinical and functional outcomes of knee arthroplasties performed using computer-assisted techniques. Copyright © 2011 Elsevier Inc. All rights reserved.

The NASA Ames PAH IR Spectroscopic Database: Computational Version 3.00 with Updated Content and the Introduction of Multiple Scaling Factors

NASA Astrophysics Data System (ADS)

Bauschlicher, Charles W., Jr.; Ricca, A.; Boersma, C.; Allamandola, L. J.

2018-02-01

Version 3.00 of the library of computed spectra in the NASA Ames PAH IR Spectroscopic Database (PAHdb) is described. Version 3.00 introduces the use of multiple scale factors, instead of the single scaling factor used previously, to align the theoretical harmonic frequencies with the experimental fundamentals. The use of multiple scale factors permits the use of a variety of basis sets; this allows new PAH species to be included in the database, such as those containing oxygen, and yields an improved treatment of strained species and those containing nitrogen. In addition, the computed spectra of 2439 new PAH species have been added. The impact of these changes on the analysis of an astronomical spectrum through database-fitting is considered and compared with a fit using Version 2.00 of the library of computed spectra. Finally, astronomical constraints are defined for the PAH spectral libraries in PAHdb.

Automated Stitching of Microtubule Centerlines across Serial Electron Tomograms

PubMed Central

Weber, Britta; Tranfield, Erin M.; Höög, Johanna L.; Baum, Daniel; Antony, Claude; Hyman, Tony; Verbavatz, Jean-Marc; Prohaska, Steffen

2014-01-01

Tracing microtubule centerlines in serial section electron tomography requires microtubules to be stitched across sections, that is lines from different sections need to be aligned, endpoints need to be matched at section boundaries to establish a correspondence between neighboring sections, and corresponding lines need to be connected across multiple sections. We present computational methods for these tasks: 1) An initial alignment is computed using a distance compatibility graph. 2) A fine alignment is then computed with a probabilistic variant of the iterative closest points algorithm, which we extended to handle the orientation of lines by introducing a periodic random variable to the probabilistic formulation. 3) Endpoint correspondence is established by formulating a matching problem in terms of a Markov random field and computing the best matching with belief propagation. Belief propagation is not generally guaranteed to converge to a minimum. We show how convergence can be achieved, nonetheless, with minimal manual input. In addition to stitching microtubule centerlines, the correspondence is also applied to transform and merge the electron tomograms. We applied the proposed methods to samples from the mitotic spindle in C. elegans, the meiotic spindle in X. laevis, and sub-pellicular microtubule arrays in T. brucei. The methods were able to stitch microtubules across section boundaries in good agreement with experts' opinions for the spindle samples. Results, however, were not satisfactory for the microtubule arrays. For certain experiments, such as an analysis of the spindle, the proposed methods can replace manual expert tracing and thus enable the analysis of microtubules over long distances with reasonable manual effort. PMID:25438148

Automated stitching of microtubule centerlines across serial electron tomograms.

PubMed

Weber, Britta; Tranfield, Erin M; Höög, Johanna L; Baum, Daniel; Antony, Claude; Hyman, Tony; Verbavatz, Jean-Marc; Prohaska, Steffen

2014-01-01

Tracing microtubule centerlines in serial section electron tomography requires microtubules to be stitched across sections, that is lines from different sections need to be aligned, endpoints need to be matched at section boundaries to establish a correspondence between neighboring sections, and corresponding lines need to be connected across multiple sections. We present computational methods for these tasks: 1) An initial alignment is computed using a distance compatibility graph. 2) A fine alignment is then computed with a probabilistic variant of the iterative closest points algorithm, which we extended to handle the orientation of lines by introducing a periodic random variable to the probabilistic formulation. 3) Endpoint correspondence is established by formulating a matching problem in terms of a Markov random field and computing the best matching with belief propagation. Belief propagation is not generally guaranteed to converge to a minimum. We show how convergence can be achieved, nonetheless, with minimal manual input. In addition to stitching microtubule centerlines, the correspondence is also applied to transform and merge the electron tomograms. We applied the proposed methods to samples from the mitotic spindle in C. elegans, the meiotic spindle in X. laevis, and sub-pellicular microtubule arrays in T. brucei. The methods were able to stitch microtubules across section boundaries in good agreement with experts' opinions for the spindle samples. Results, however, were not satisfactory for the microtubule arrays. For certain experiments, such as an analysis of the spindle, the proposed methods can replace manual expert tracing and thus enable the analysis of microtubules over long distances with reasonable manual effort.

Multiple-bolted joints in wood members : a literature review

Treesearch

Peter James Moss

1997-01-01

This study reviewed the literature on experimental and analytical research for the connection of wood members using multiple laterally loaded bolts. From this, the influence of geometric factors were ascertained, such as staggered and aligned fasteners, optimum fastener configurations, row factors and length-to-diameter bolt ratios, spacing, end and edge distances, and...

Coh-Metrix Measures Text Characteristics at Multiple Levels of Language and Discourse

ERIC Educational Resources Information Center

Graesser, Arthur C.; McNamara, Danielle S.; Cai, Zhiqiang; Conley, Mark; Li, Haiying; Pennebaker, James

2014-01-01

Coh-Metrix analyzes texts on multiple measures of language and discourse that are aligned with multilevel theoretical frameworks of comprehension. Dozens of measures funnel into five major factors that systematically vary as a function of types of texts (e.g., narrative vs. informational) and grade level: narrativity, syntactic simplicity, word…

Multi-scale pixel-based image fusion using multivariate empirical mode decomposition.

PubMed

Rehman, Naveed ur; Ehsan, Shoaib; Abdullah, Syed Muhammad Umer; Akhtar, Muhammad Jehanzaib; Mandic, Danilo P; McDonald-Maier, Klaus D

2015-05-08

A novel scheme to perform the fusion of multiple images using the multivariate empirical mode decomposition (MEMD) algorithm is proposed. Standard multi-scale fusion techniques make a priori assumptions regarding input data, whereas standard univariate empirical mode decomposition (EMD)-based fusion techniques suffer from inherent mode mixing and mode misalignment issues, characterized respectively by either a single intrinsic mode function (IMF) containing multiple scales or the same indexed IMFs corresponding to multiple input images carrying different frequency information. We show that MEMD overcomes these problems by being fully data adaptive and by aligning common frequency scales from multiple channels, thus enabling their comparison at a pixel level and subsequent fusion at multiple data scales. We then demonstrate the potential of the proposed scheme on a large dataset of real-world multi-exposure and multi-focus images and compare the results against those obtained from standard fusion algorithms, including the principal component analysis (PCA), discrete wavelet transform (DWT) and non-subsampled contourlet transform (NCT). A variety of image fusion quality measures are employed for the objective evaluation of the proposed method. We also report the results of a hypothesis testing approach on our large image dataset to identify statistically-significant performance differences.

Multi-Scale Pixel-Based Image Fusion Using Multivariate Empirical Mode Decomposition

PubMed Central

Rehman, Naveed ur; Ehsan, Shoaib; Abdullah, Syed Muhammad Umer; Akhtar, Muhammad Jehanzaib; Mandic, Danilo P.; McDonald-Maier, Klaus D.

2015-01-01

A novel scheme to perform the fusion of multiple images using the multivariate empirical mode decomposition (MEMD) algorithm is proposed. Standard multi-scale fusion techniques make a priori assumptions regarding input data, whereas standard univariate empirical mode decomposition (EMD)-based fusion techniques suffer from inherent mode mixing and mode misalignment issues, characterized respectively by either a single intrinsic mode function (IMF) containing multiple scales or the same indexed IMFs corresponding to multiple input images carrying different frequency information. We show that MEMD overcomes these problems by being fully data adaptive and by aligning common frequency scales from multiple channels, thus enabling their comparison at a pixel level and subsequent fusion at multiple data scales. We then demonstrate the potential of the proposed scheme on a large dataset of real-world multi-exposure and multi-focus images and compare the results against those obtained from standard fusion algorithms, including the principal component analysis (PCA), discrete wavelet transform (DWT) and non-subsampled contourlet transform (NCT). A variety of image fusion quality measures are employed for the objective evaluation of the proposed method. We also report the results of a hypothesis testing approach on our large image dataset to identify statistically-significant performance differences. PMID:26007714

Identification and sequence analyses of novel lipase encoding novel thermophillic bacilli isolated from Armenian geothermal springs.

PubMed

Shahinyan, Grigor; Margaryan, Armine; Panosyan, Hovik; Trchounian, Armen

2017-05-02

Among the huge diversity of thermophilic bacteria mainly bacilli have been reported as active thermostable lipase producers. Geothermal springs serve as the main source for isolation of thermostable lipase producing bacilli. Thermostable lipolytic enzymes, functioning in the harsh conditions, have promising applications in processing of organic chemicals, detergent formulation, synthesis of biosurfactants, pharmaceutical processing etc. In order to study the distribution of lipase-producing thermophilic bacilli and their specific lipase protein primary structures, three lipase producers from different genera were isolated from mesothermal (27.5-70 °C) springs distributed on the territory of Armenia and Nagorno Karabakh. Based on phenotypic characteristics and 16S rRNA gene sequencing the isolates were identified as Geobacillus sp., Bacillus licheniformis and Anoxibacillus flavithermus strains. The lipase genes of isolates were sequenced by using initially designed primer sets. Multiple alignments generated from primary structures of the lipase proteins and annotated lipase protein sequences, conserved regions analysis and amino acid composition have illustrated the similarity (98-99%) of the lipases with true lipases (family I) and GDSL esterase family (family II). A conserved sequence block that determines the thermostability has been identified in the multiple alignments of the lipase proteins. The results are spreading light on the lipase producing bacilli distribution in geothermal springs in Armenia and Nagorno Karabakh. Newly isolated bacilli strains could be prospective source for thermostable lipases and their genes.

An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data.

PubMed

Vu, Trung N; Valkenborg, Dirk; Smets, Koen; Verwaest, Kim A; Dommisse, Roger; Lemière, Filip; Verschoren, Alain; Goethals, Bart; Laukens, Kris

2011-10-20

Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline. We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data. The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from http://code.google.com/p/speaq/.

Photo-consistency registration of a 4D cardiac motion model to endoscopic video for image guidance of robotic coronary artery bypass

NASA Astrophysics Data System (ADS)

Figl, Michael; Rueckert, Daniel; Edwards, Eddie

2009-02-01

The aim of the work described in this paper is registration of a 4D preoperative motion model of the heart to the video view of the patient through the intraoperative endoscope. The heart motion is cyclical and can be modelled using multiple reconstructions of cardiac gated coronary CT. We propose the use of photoconsistency between the two views through the da Vinci endoscope to align to the preoperative heart surface model from CT. The temporal alignment from the video to the CT model could in principle be obtained from the ECG signal. We propose averaging of the photoconsistency over the cardiac cycle to improve the registration compared to a single view. Though there is considerable motion of the heart, after correct temporal alignment we suggest that the remaining motion should be close to rigid. Results are presented for simulated renderings and for real video of a beating heart phantom. We found much smoother sections at the minimum when using multiple phases for the registration, furthermore convergence was found to be better when more phases are used.

Using hidden Markov models to align multiple sequences.

PubMed

Mount, David W

2009-07-01

A hidden Markov model (HMM) is a probabilistic model of a multiple sequence alignment (msa) of proteins. In the model, each column of symbols in the alignment is represented by a frequency distribution of the symbols (called a "state"), and insertions and deletions are represented by other states. One moves through the model along a particular path from state to state in a Markov chain (i.e., random choice of next move), trying to match a given sequence. The next matching symbol is chosen from each state, recording its probability (frequency) and also the probability of going to that state from a previous one (the transition probability). State and transition probabilities are multiplied to obtain a probability of the given sequence. The hidden nature of the HMM is due to the lack of information about the value of a specific state, which is instead represented by a probability distribution over all possible values. This article discusses the advantages and disadvantages of HMMs in msa and presents algorithms for calculating an HMM and the conditions for producing the best HMM.

CoSMoS: Conserved Sequence Motif Search in the proteome

PubMed Central

Liu, Xiao I; Korde, Neeraj; Jakob, Ursula; Leichert, Lars I

2006-01-01

Background With the ever-increasing number of gene sequences in the public databases, generating and analyzing multiple sequence alignments becomes increasingly time consuming. Nevertheless it is a task performed on a regular basis by researchers in many labs. Results We have now created a database called CoSMoS to find the occurrences and at the same time evaluate the significance of sequence motifs and amino acids encoded in the whole genome of the model organism Escherichia coli K12. We provide a precomputed set of multiple sequence alignments for each individual E. coli protein with all of its homologues in the RefSeq database. The alignments themselves, information about the occurrence of sequence motifs together with information on the conservation of each of the more than 1.3 million amino acids encoded in the E. coli genome can be accessed via the web interface of CoSMoS. Conclusion CoSMoS is a valuable tool to identify highly conserved sequence motifs, to find regions suitable for mutational studies in functional analyses and to predict important structural features in E. coli proteins. PMID:16433915

High-speed peak matching algorithm for retention time alignment of gas chromatographic data for chemometric analysis.

PubMed

Johnson, Kevin J; Wright, Bob W; Jarman, Kristin H; Synovec, Robert E

2003-05-09

A rapid retention time alignment algorithm was developed as a preprocessing utility to be used prior to chemometric analysis of large datasets of diesel fuel profiles obtained using gas chromatography (GC). Retention time variation from chromatogram-to-chromatogram has been a significant impediment against the use of chemometric techniques in the analysis of chromatographic data due to the inability of current chemometric techniques to correctly model information that shifts from variable to variable within a dataset. The alignment algorithm developed is shown to increase the efficacy of pattern recognition methods applied to diesel fuel chromatograms by retaining chemical selectivity while reducing chromatogram-to-chromatogram retention time variations and to do so on a time scale that makes analysis of large sets of chromatographic data practical. Two sets of diesel fuel gas chromatograms were studied using the novel alignment algorithm followed by principal component analysis (PCA). In the first study, retention times for corresponding chromatographic peaks in 60 chromatograms varied by as much as 300 ms between chromatograms before alignment. In the second study of 42 chromatograms, the retention time shifting exhibited was on the order of 10 s between corresponding chromatographic peaks, and required a coarse retention time correction prior to alignment with the algorithm. In both cases, an increase in retention time precision afforded by the algorithm was clearly visible in plots of overlaid chromatograms before and then after applying the retention time alignment algorithm. Using the alignment algorithm, the standard deviation for corresponding peak retention times following alignment was 17 ms throughout a given chromatogram, corresponding to a relative standard deviation of 0.003% at an average retention time of 8 min. This level of retention time precision is a 5-fold improvement over the retention time precision initially provided by a state-of-the-art GC instrument equipped with electronic pressure control and was critical to the performance of the chemometric analysis. This increase in retention time precision does not come at the expense of chemical selectivity, since the PCA results suggest that essentially all of the chemical selectivity is preserved. Cluster resolution between dissimilar groups of diesel fuel chromatograms in a two-dimensional scores space generated with PCA is shown to substantially increase after alignment. The alignment method is robust against missing or extra peaks relative to a target chromatogram used in the alignment, and operates at high speed, requiring roughly 1 s of computation time per GC chromatogram.

A comparative study of RNA-Seq and microarray data analysis on the two examples of rectal-cancer patients and Burkitt Lymphoma cells.

PubMed

Wolff, Alexander; Bayerlová, Michaela; Gaedcke, Jochen; Kube, Dieter; Beißbarth, Tim

2018-01-01

Pipeline comparisons for gene expression data are highly valuable for applied real data analyses, as they enable the selection of suitable analysis strategies for the dataset at hand. Such pipelines for RNA-Seq data should include mapping of reads, counting and differential gene expression analysis or preprocessing, normalization and differential gene expression in case of microarray analysis, in order to give a global insight into pipeline performances. Four commonly used RNA-Seq pipelines (STAR/HTSeq-Count/edgeR, STAR/RSEM/edgeR, Sailfish/edgeR, TopHat2/Cufflinks/CuffDiff)) were investigated on multiple levels (alignment and counting) and cross-compared with the microarray counterpart on the level of gene expression and gene ontology enrichment. For these comparisons we generated two matched microarray and RNA-Seq datasets: Burkitt Lymphoma cell line data and rectal cancer patient data. The overall mapping rate of STAR was 98.98% for the cell line dataset and 98.49% for the patient dataset. Tophat's overall mapping rate was 97.02% and 96.73%, respectively, while Sailfish had only an overall mapping rate of 84.81% and 54.44%. The correlation of gene expression in microarray and RNA-Seq data was moderately worse for the patient dataset (ρ = 0.67-0.69) than for the cell line dataset (ρ = 0.87-0.88). An exception were the correlation results of Cufflinks, which were substantially lower (ρ = 0.21-0.29 and 0.34-0.53). For both datasets we identified very low numbers of differentially expressed genes using the microarray platform. For RNA-Seq we checked the agreement of differentially expressed genes identified in the different pipelines and of GO-term enrichment results. In conclusion the combination of STAR aligner with HTSeq-Count followed by STAR aligner with RSEM and Sailfish generated differentially expressed genes best suited for the dataset at hand and in agreement with most of the other transcriptomics pipelines.

Independent Metrics for Protein Backbone and Side-Chain Flexibility: Time Scales and Effects of Ligand Binding.

PubMed

Fuchs, Julian E; Waldner, Birgit J; Huber, Roland G; von Grafenstein, Susanne; Kramer, Christian; Liedl, Klaus R

2015-03-10

Conformational dynamics are central for understanding biomolecular structure and function, since biological macromolecules are inherently flexible at room temperature and in solution. Computational methods are nowadays capable of providing valuable information on the conformational ensembles of biomolecules. However, analysis tools and intuitive metrics that capture dynamic information from in silico generated structural ensembles are limited. In standard work-flows, flexibility in a conformational ensemble is represented through residue-wise root-mean-square fluctuations or B-factors following a global alignment. Consequently, these approaches relying on global alignments discard valuable information on local dynamics. Results inherently depend on global flexibility, residue size, and connectivity. In this study we present a novel approach for capturing positional fluctuations based on multiple local alignments instead of one single global alignment. The method captures local dynamics within a structural ensemble independent of residue type by splitting individual local and global degrees of freedom of protein backbone and side-chains. Dependence on residue type and size in the side-chains is removed via normalization with the B-factors of the isolated residue. As a test case, we demonstrate its application to a molecular dynamics simulation of bovine pancreatic trypsin inhibitor (BPTI) on the millisecond time scale. This allows for illustrating different time scales of backbone and side-chain flexibility. Additionally, we demonstrate the effects of ligand binding on side-chain flexibility of three serine proteases. We expect our new methodology for quantifying local flexibility to be helpful in unraveling local changes in biomolecular dynamics.

Peptide aptamer-assisted immobilization of green fluorescent protein for creating biomolecule-complexed carbon nanotube device

NASA Astrophysics Data System (ADS)

Nii, Daisuke; Nozawa, Yosuke; Miyachi, Mariko; Yamanoi, Yoshinori; Nishihara, Hiroshi; Tomo, Tatsuya; Shimada, Yuichiro

2017-10-01

Carbon nanotubes are a novel material for next-generation applications. In this study, we generated carbon nanotube and green fluorescent protein (GFP) conjugates using affinity binding peptides. The carbon nanotube-binding motif was introduced into the N-terminus of the GFP through molecular biology methods. Multiple GFPs were successfully aligned on a single-walled carbon nanotube via the molecular recognition function of the peptide aptamer, which was confirmed through transmission electron microscopy and optical analysis. Fluorescence spectral analysis results also suggested that the carbon nanotube-GFP complex was autonomously formed with orientation and without causing protein denaturation during immobilization. This simple process has a widespread potential for fabricating carbon nanotube-biomolecule hybrid devices.

Seeking an Anchorage. Stability and Variability in Tonal Alignment of Rising Prenuclear Pitch Accents in Cypriot Greek.

PubMed

Themistocleous, Charalambos

2016-12-01

Although tonal alignment constitutes a quintessential property of pitch accents, its exact characteristics remain unclear. This study, by exploring the timing of the Cypriot Greek L*+H prenuclear pitch accent, examines the predictions of three hypotheses about tonal alignment: the invariance hypothesis, the segmental anchoring hypothesis, and the segmental anchorage hypothesis. The study reports on two experiments: the first of which manipulates the syllable patterns of the stressed syllable, and the second of which modifies the distance of the L*+H from the following pitch accent. The findings on the alignment of the low tone (L) are illustrative of the segmental anchoring hypothesis predictions: the L persistently aligns inside the onset consonant, a few milliseconds before the stressed vowel. However, the findings on the alignment of the high tone (H) are both intriguing and unexpected: the alignment of the H depends on the number of unstressed syllables that follow the prenuclear pitch accent. The 'wandering' of the H over multiple syllables is extremely rare among languages, and casts doubt on the invariance hypothesis and the segmental anchoring hypothesis, as well as indicating the need for a modified version of the segmental anchorage hypothesis. To address the alignment of the H, we suggest that it aligns within a segmental anchorage-the area that follows the prenuclear pitch accent-in such a way as to protect the paradigmatic contrast between the L*+H prenuclear pitch accent and the L+H* nuclear pitch accent.

CAFE: aCcelerated Alignment-FrEe sequence analysis

PubMed Central

Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A.; Waterman, Michael S.

2017-01-01

Abstract Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$d_2^*$\\end{document} and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$d_2^S$\\end{document} are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. PMID:28472388

Centroid stabilization for laser alignment to corner cubes: designing a matched filter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awwal, Abdul A. S.; Bliss, Erlan; Brunton, Gordon

2016-11-08

Automation of image-based alignment of National Ignition Facility high energy laser beams is providing the capability of executing multiple target shots per day. One important alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retroreflecting corner cubes as centering references for each beam. Beam-to-beam variations and systematic beam changes over time in the FOA corner cube images can lead to a reduction in accuracy as well as increased convergence durations for the template-based position detector. A systematic approach is described that maintains FOA corner cube templates and guaranteesmore » stable position estimation.« less

Centroid stabilization for laser alignment to corner cubes: designing a matched filter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awwal, Abdul A. S.; Bliss, Erlan; Brunton, Gordon

2016-11-08

Automation of image-based alignment of NIF high energy laser beams is providing the capability of executing multiple target shots per day. One important alignment is beam centration through the second and third harmonic generating crystals in the final optics assembly (FOA), which employs two retro-reflecting corner cubes as centering references for each beam. Beam-to-beam variations and systematic beam changes over time in the FOA corner cube images can lead to a reduction in accuracy as well as increased convergence durations for the template-based position detector. A systematic approach is described that maintains FOA corner cube templates and guarantees stable positionmore » estimation.« less

MetAlign 3.0: performance enhancement by efficient use of advances in computer hardware.

PubMed

Lommen, Arjen; Kools, Harrie J

2012-08-01

A new, multi-threaded version of the GC-MS and LC-MS data processing software, metAlign, has been developed which is able to utilize multiple cores on one PC. This new version was tested using three different multi-core PCs with different operating systems. The performance of noise reduction, baseline correction and peak-picking was 8-19 fold faster compared to the previous version on a single core machine from 2008. The alignment was 5-10 fold faster. Factors influencing the performance enhancement are discussed. Our observations show that performance scales with the increase in processor core numbers we currently see in consumer PC hardware development.

Thermal resilient multiple jaw braze fixture

DOEpatents

Ney, R.; Perrone, A.J.

1995-07-11

A braze fixture has side walls forming a cavity with an opening to receive a stack of parts to be brazed. Sidewalls of the housing have a plurality of bearing receiving openings into which bearing rods or jaws are inserted to align the stacked elements of the workpiece. The housing can also have view ports to allow a visual check of the alignment. Straps or wires around the fixture are selected to have thermal characteristics similar to the thermal characteristics of the workpiece undergoing brazing. The straps or wires make physical contact with the bearing rods thereby causing bearing rods to maintain the workpiece in proper alignment throughout the entire brazing cycle. 9 figs.

An Alignment Model for Collaborative Value Networks

NASA Astrophysics Data System (ADS)

Bremer, Carlos; Azevedo, Rodrigo Cambiaghi; Klen, Alexandra Pereira

This paper presents parts of the work carried out in several global organizations through the development of strategic projects with high tactical and operational complexity. By investing in long-term relationships, strongly operating in the transformation of the competitive model and focusing on the value chain management, the main aim of these projects was the alignment of multiple value chains. The projects were led by the Axia Transformation Methodology as well as by its Management Model and following the principles of Project Management. As a concrete result of the efforts made in the last years in the Brazilian market this work also introduces the Alignment Model which supports the transformation process that the companies undergo.

Multiview echocardiography fusion using an electromagnetic tracking system.

PubMed

Punithakumar, Kumaradevan; Hareendranathan, Abhilash R; Paakkanen, Riitta; Khan, Nehan; Noga, Michelle; Boulanger, Pierre; Becher, Harald

2016-08-01

Three-dimensional ultrasound is an emerging modality for the assessment of complex cardiac anatomy and function. The advantages of this modality include lack of ionizing radiation, portability, low cost, and high temporal resolution. Major limitations include limited field-of-view, reliance on frequently limited acoustic windows, and poor signal to noise ratio. This study proposes a novel approach to combine multiple views into a single image using an electromagnetic tracking system in order to improve the field-of-view. The novel method has several advantages: 1) it does not rely on image information for alignment, and therefore, the method does not require image overlap; 2) the alignment accuracy of the proposed approach is not affected by any poor image quality as in the case of image registration based approaches; 3) in contrast to previous optical tracking based system, the proposed approach does not suffer from line-of-sight limitation; and 4) it does not require any initial calibration. In this pilot project, we were able to show that using a heart phantom, our method can fuse multiple echocardiographic images and improve the field-of view. Quantitative evaluations showed that the proposed method yielded a nearly optimal alignment of image data sets in three-dimensional space. The proposed method demonstrates the electromagnetic system can be used for the fusion of multiple echocardiography images with a seamless integration of sensors to the transducer.

Self-aligning hydraulic piston assembly for tensile testing of ceramic

DOEpatents

Liu, Kenneth C.

1987-01-01

The present invention is directed to a self-aligning grip housing assembly that can transmit an uniaxial load to a tensil specimen without introducing bending stresses into the specimen. Disposed inside said grip housing assembly are a multiplicity of supporting pistons connected to a common source of pressurized oil that carry equal shares of the load applied to the specimen irregardless whether there is initial misalignment between the specimen load column assembly and housing axis.

Linear Transceiver Design for Interference Alignment: Complexity and Computation

DTIC Science & Technology

2010-07-01

restriction on the choice of beamforming vector of node b. Thus, for any fixed transmit node b in H , there are multiple restriction sets, each...signal space can be chosen. The receive nodes in H can achieve interference alignment if and only if these restricted sets of one-dimensional signal...total number of restriction sets is at most linear in the number of edges in H and each restriction set contains at most two one-dimensional

Self-aligning hydraulic piston assembly for tensile testing of ceramic

DOEpatents

Liu, K.C.

1987-08-18

The present invention is directed to a self-aligning grip housing assembly that can transmit an uniaxial load to a tensile specimen without introducing bending stresses into the specimen. Disposed inside said grip housing assembly are a multiplicity of supporting pistons connected to a common source of pressurized oil that carry equal shares of the load applied to the specimen regardless whether there is initial misalignment between the specimen load column assembly and housing axis. 4 figs.

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

Query-seeded iterative sequence similarity searching improves selectivity 5–20-fold

PubMed Central

Li, Weizhong; Lopez, Rodrigo

2017-01-01

Abstract Iterative similarity search programs, like psiblast, jackhmmer, and psisearch, are much more sensitive than pairwise similarity search methods like blast and ssearch because they build a position specific scoring model (a PSSM or HMM) that captures the pattern of sequence conservation characteristic to a protein family. But models are subject to contamination; once an unrelated sequence has been added to the model, homologs of the unrelated sequence will also produce high scores, and the model can diverge from the original protein family. Examination of alignment errors during psiblast PSSM contamination suggested a simple strategy for dramatically reducing PSSM contamination. psiblast PSSMs are built from the query-based multiple sequence alignment (MSA) implied by the pairwise alignments between the query model (PSSM, HMM) and the subject sequences in the library. When the original query sequence residues are inserted into gapped positions in the aligned subject sequence, the resulting PSSM rarely produces alignment over-extensions or alignments to unrelated sequences. This simple step, which tends to anchor the PSSM to the original query sequence and slightly increase target percent identity, can reduce the frequency of false-positive alignments more than 20-fold compared with psiblast and jackhmmer, with little loss in search sensitivity. PMID:27923999

Parallel algorithms for large-scale biological sequence alignment on Xeon-Phi based clusters.

PubMed

Lan, Haidong; Chan, Yuandong; Xu, Kai; Schmidt, Bertil; Peng, Shaoliang; Liu, Weiguo

2016-07-19

Computing alignments between two or more sequences are common operations frequently performed in computational molecular biology. The continuing growth of biological sequence databases establishes the need for their efficient parallel implementation on modern accelerators. This paper presents new approaches to high performance biological sequence database scanning with the Smith-Waterman algorithm and the first stage of progressive multiple sequence alignment based on the ClustalW heuristic on a Xeon Phi-based compute cluster. Our approach uses a three-level parallelization scheme to take full advantage of the compute power available on this type of architecture; i.e. cluster-level data parallelism, thread-level coarse-grained parallelism, and vector-level fine-grained parallelism. Furthermore, we re-organize the sequence datasets and use Xeon Phi shuffle operations to improve I/O efficiency. Evaluations show that our method achieves a peak overall performance up to 220 GCUPS for scanning real protein sequence databanks on a single node consisting of two Intel E5-2620 CPUs and two Intel Xeon Phi 7110P cards. It also exhibits good scalability in terms of sequence length and size, and number of compute nodes for both database scanning and multiple sequence alignment. Furthermore, the achieved performance is highly competitive in comparison to optimized Xeon Phi and GPU implementations. Our implementation is available at https://github.com/turbo0628/LSDBS-mpi .

New nurse transition: success through aligning multiple identities.

PubMed

Leong, Yee Mun Jessica; Crossman, Joanna

2015-01-01

The purpose of this paper is to explore the perceptions of new nurses in Singapore of their experiences of role transition and to examine the implications for managers in terms of employee training, development and retention. This qualitative study was conducted using a constructivist grounded theory approach. In total 26 novice nurses and five preceptors (n=31) from five different hospitals participated in the study. Data were collected from semi-structured interviews and reflective journal entries and analysed using the constant comparative method. The findings revealed that novice nurses remained emotionally and physically challenged when experiencing role transition. Two major constructs appear to play an important part in the transition process; learning how to Fit in and aligning personal with professional and organisational identities. The findings highlight factors that facilitate or impede Fitting in and aligning these identities. Although the concept of Fitting in and its relation to the attrition of novice nurses has been explored in global studies, that relationship has not yet been theorised as the dynamic alignment of multiple identities. Also, whilst most research around Fitting in, identity and retention has been conducted in western countries, little is known about these issues and their interrelationship in the context of Singapore. The study should inform decision making by healthcare organisations, nurse managers and nursing training institutions with respect to improving the transition experience of novice nurses.

De novo identification of highly diverged protein repeats by probabilistic consistency.

PubMed

Biegert, A; Söding, J

2008-03-15

An estimated 25% of all eukaryotic proteins contain repeats, which underlines the importance of duplication for evolving new protein functions. Internal repeats often correspond to structural or functional units in proteins. Methods capable of identifying diverged repeated segments or domains at the sequence level can therefore assist in predicting domain structures, inferring hypotheses about function and mechanism, and investigating the evolution of proteins from smaller fragments. We present HHrepID, a method for the de novo identification of repeats in protein sequences. It is able to detect the sequence signature of structural repeats in many proteins that have not yet been known to possess internal sequence symmetry, such as outer membrane beta-barrels. HHrepID uses HMM-HMM comparison to exploit evolutionary information in the form of multiple sequence alignments of homologs. In contrast to a previous method, the new method (1) generates a multiple alignment of repeats; (2) utilizes the transitive nature of homology through a novel merging procedure with fully probabilistic treatment of alignments; (3) improves alignment quality through an algorithm that maximizes the expected accuracy; (4) is able to identify different kinds of repeats within complex architectures by a probabilistic domain boundary detection method and (5) improves sensitivity through a new approach to assess statistical significance. Server: http://toolkit.tuebingen.mpg.de/hhrepid; Executables: ftp://ftp.tuebingen.mpg.de/pub/protevo/HHrepID

GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

PubMed

Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

2015-01-01

Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Highly aligned arrays of high aspect ratio barium titanate nanowires via hydrothermal synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowland, Christopher C.; Zhou, Zhi; Malakooti, Mohammad H.

2015-06-01

We report on the development of a hydrothermal synthesis procedure that results in the growth of highly aligned arrays of high aspect ratio barium titanate nanowires. Using a multiple step, scalable hydrothermal reaction, a textured titanium dioxide film is deposited on titanium foil upon which highly aligned nanowires are grown via homoepitaxy and converted to barium titanate. Scanning electron microscope images clearly illustrate the effect the textured film has on the degree of orientation of the nanowires. The alignment of nanowires is quantified by calculating the Herman's Orientation Factor, which reveals a 58% improvement in orientation as compared to growthmore » in the absence of the textured film. The ferroelectric properties of barium titanate combined with the development of this scalable growth procedure provide a powerful route towards increasing the efficiency and performance of nanowire-based devices in future real-world applications such as sensing and power harvesting.« less

Sleeve Push Technique: A Novel Method of Space Gaining.

PubMed

Verma, Sanjeev; Bhupali, Nameksh Raj; Gupta, Deepak Kumar; Singh, Sombir; Singh, Satinder Pal

2018-01-01

Space gaining is frequently required in orthodontics. Multiple loops were initially used for space gaining and alignment. The most common used mechanics for space gaining is the use of nickel-titanium open coil springs. The disadvantage of nickel-titanium coil spring is that they cannot be used until the arches are well aligned to receive the stiffer stainless steel wires. Therefore, a new method of gaining space during initial alignment and leveling has been developed and named as sleeve push technique (SPT). The nickel-titanium wires, i.e. 0.012 inches and 0.014 inches along with archwire sleeve (protective tubing) can be used in a modified way to gain space along with alignment. This method helps in gaining space right from day 1 of treatment. The archwire sleeve and nickel-titanium wire in this new SPT act as a mutually synergistic combination and provide the orthodontist with a completely new technique for space opening.

The SOAPS project - Spin-orbit alignment of planetary systems. Exoplanets' evolution histories in systems with different architectures

NASA Astrophysics Data System (ADS)

Faedi, F.; Gómez Maqueo Chew, Y.; Fossati, L.; Pollacco, D.; McQuillan, A.; Hebb, L.; Chaplin, W. J.; Aigrain, S.

2013-04-01

The wealth of information rendered by Kepler planets and planet candidates is indispensable for statistically significant studies of distinct planet populations, in both single and multiple systems. Empirical evidences suggest that Kepler's planet population shows different physical properties as compared to the bulk of known exoplanets. The SOAPS project, aims to shed light on Kepler's planets formation, their migration and architecture. By measuring v sini accurately for Kepler hosts with rotation periods measured from their high-precision light curves, we will assess the alignment of the planetary orbit with respect to the stellar spin axis. This degree of alignment traces the formation history and evolution of the planetary systems, and thus, allows to distinguish between different proposed migration theories. SOAPS will increase by a factor of 2 the number of spin-orbit alignment measurements pushing the parameters space down to the SuperEarth domain. Here we present our preliminary results.

MicRhoDE: a curated database for the analysis of microbial rhodopsin diversity and evolution

PubMed Central

Boeuf, Dominique; Audic, Stéphane; Brillet-Guéguen, Loraine; Caron, Christophe; Jeanthon, Christian

2015-01-01

Microbial rhodopsins are a diverse group of photoactive transmembrane proteins found in all three domains of life and in viruses. Today, microbial rhodopsin research is a flourishing research field in which new understandings of rhodopsin diversity, function and evolution are contributing to broader microbiological and molecular knowledge. Here, we describe MicRhoDE, a comprehensive, high-quality and freely accessible database that facilitates analysis of the diversity and evolution of microbial rhodopsins. Rhodopsin sequences isolated from a vast array of marine and terrestrial environments were manually collected and curated. To each rhodopsin sequence are associated related metadata, including predicted spectral tuning of the protein, putative activity and function, taxonomy for sequences that can be linked to a 16S rRNA gene, sampling date and location, and supporting literature. The database currently covers 7857 aligned sequences from more than 450 environmental samples or organisms. Based on a robust phylogenetic analysis, we introduce an operational classification system with multiple phylogenetic levels ranging from superclusters to species-level operational taxonomic units. An integrated pipeline for online sequence alignment and phylogenetic tree construction is also provided. With a user-friendly interface and integrated online bioinformatics tools, this unique resource should be highly valuable for upcoming studies of the biogeography, diversity, distribution and evolution of microbial rhodopsins. Database URL: http://micrhode.sb-roscoff.fr. PMID:26286928

MicRhoDE: a curated database for the analysis of microbial rhodopsin diversity and evolution.

PubMed

Boeuf, Dominique; Audic, Stéphane; Brillet-Guéguen, Loraine; Caron, Christophe; Jeanthon, Christian

2015-01-01

Microbial rhodopsins are a diverse group of photoactive transmembrane proteins found in all three domains of life and in viruses. Today, microbial rhodopsin research is a flourishing research field in which new understandings of rhodopsin diversity, function and evolution are contributing to broader microbiological and molecular knowledge. Here, we describe MicRhoDE, a comprehensive, high-quality and freely accessible database that facilitates analysis of the diversity and evolution of microbial rhodopsins. Rhodopsin sequences isolated from a vast array of marine and terrestrial environments were manually collected and curated. To each rhodopsin sequence are associated related metadata, including predicted spectral tuning of the protein, putative activity and function, taxonomy for sequences that can be linked to a 16S rRNA gene, sampling date and location, and supporting literature. The database currently covers 7857 aligned sequences from more than 450 environmental samples or organisms. Based on a robust phylogenetic analysis, we introduce an operational classification system with multiple phylogenetic levels ranging from superclusters to species-level operational taxonomic units. An integrated pipeline for online sequence alignment and phylogenetic tree construction is also provided. With a user-friendly interface and integrated online bioinformatics tools, this unique resource should be highly valuable for upcoming studies of the biogeography, diversity, distribution and evolution of microbial rhodopsins. Database URL: http://micrhode.sb-roscoff.fr. © The Author(s) 2015. Published by Oxford University Press.

Forced Alignment for Understudied Language Varieties: Testing Prosodylab-Aligner with Tongan Data

ERIC Educational Resources Information Center

Johnson, Lisa M.; Di Paolo, Marianna; Bell, Adrian

2018-01-01

Automated alignment of transcriptions to audio files expedites the process of preparing data for acoustic analysis. Unfortunately, the benefits of auto-alignment have generally been available only to researchers studying majority languages, for which large corpora exist and for which acoustic models have been created by large-scale research…

Sub-Diffraction Limited Writing based on Laser Induced Periodic Surface Structures (LIPSS).

PubMed

He, Xiaolong; Datta, Anurup; Nam, Woongsik; Traverso, Luis M; Xu, Xianfan

2016-10-10

Controlled fabrication of single and multiple nanostructures far below the diffraction limit using a method based on laser induced periodic surface structure (LIPSS) is presented. In typical LIPSS, multiple lines with a certain spatial periodicity, but often not well-aligned, were produced. In this work, well-controlled and aligned nanowires and nanogrooves with widths as small as 40 nm and 60 nm with desired orientation and length are fabricated. Moreover, single nanowire and nanogroove were fabricated based on the same mechanism for forming multiple, periodic structures. Combining numerical modeling and AFM/SEM analyses, it was found these nanostructures were formed through the interference between the incident laser radiation and the surface plasmons, the mechanism for forming LIPSS on a dielectric surface using a high power femtosecond laser. We expect that our method, in particular, the fabrication of single nanowires and nanogrooves could be a promising alternative for fabrication of nanoscale devices due to its simplicity, flexibility, and versatility.

Sub-Diffraction Limited Writing based on Laser Induced Periodic Surface Structures (LIPSS)

PubMed Central

He, Xiaolong; Datta, Anurup; Nam, Woongsik; Traverso, Luis M.; Xu, Xianfan

2016-01-01

Controlled fabrication of single and multiple nanostructures far below the diffraction limit using a method based on laser induced periodic surface structure (LIPSS) is presented. In typical LIPSS, multiple lines with a certain spatial periodicity, but often not well-aligned, were produced. In this work, well-controlled and aligned nanowires and nanogrooves with widths as small as 40 nm and 60 nm with desired orientation and length are fabricated. Moreover, single nanowire and nanogroove were fabricated based on the same mechanism for forming multiple, periodic structures. Combining numerical modeling and AFM/SEM analyses, it was found these nanostructures were formed through the interference between the incident laser radiation and the surface plasmons, the mechanism for forming LIPSS on a dielectric surface using a high power femtosecond laser. We expect that our method, in particular, the fabrication of single nanowires and nanogrooves could be a promising alternative for fabrication of nanoscale devices due to its simplicity, flexibility, and versatility. PMID:27721428

Attenuation-emission alignment in cardiac PET∕CT based on consistency conditions

PubMed Central

Alessio, Adam M.; Kinahan, Paul E.; Champley, Kyle M.; Caldwell, James H.

2010-01-01

Purpose: In cardiac PET and PET∕CT imaging, misaligned transmission and emission images are a common problem due to respiratory and cardiac motion. This misalignment leads to erroneous attenuation correction and can cause errors in perfusion mapping and quantification. This study develops and tests a method for automated alignment of attenuation and emission data. Methods: The CT-based attenuation map is iteratively transformed until the attenuation corrected emission data minimize an objective function based on the Radon consistency conditions. The alignment process is derived from previous work by Welch et al. [“Attenuation correction in PET using consistency information,” IEEE Trans. Nucl. Sci. 45, 3134–3141 (1998)] for stand-alone PET imaging. The process was evaluated with the simulated data and measured patient data from multiple cardiac ammonia PET∕CT exams. The alignment procedure was applied to simulations of five different noise levels with three different initial attenuation maps. For the measured patient data, the alignment procedure was applied to eight attenuation-emission combinations with initially acceptable alignment and eight combinations with unacceptable alignment. The initially acceptable alignment studies were forced out of alignment a known amount and quantitatively evaluated for alignment and perfusion accuracy. The initially unacceptable studies were compared to the proposed aligned images in a blinded side-by-side review. Results: The proposed automatic alignment procedure reduced errors in the simulated data and iteratively approaches global minimum solutions with the patient data. In simulations, the alignment procedure reduced the root mean square error to less than 5 mm and reduces the axial translation error to less than 1 mm. In patient studies, the procedure reduced the translation error by >50% and resolved perfusion artifacts after a known misalignment for the eight initially acceptable patient combinations. The side-by-side review of the proposed aligned attenuation-emission maps and initially misaligned attenuation-emission maps revealed that reviewers preferred the proposed aligned maps in all cases, except one inconclusive case. Conclusions: The proposed alignment procedure offers an automatic method to reduce attenuation correction artifacts in cardiac PET∕CT and provides a viable supplement to subjective manual realignment tools. PMID:20384256

Strategy for reliable strain measurement in InAs/GaAs materials from high-resolution Z-contrast STEM images

NASA Astrophysics Data System (ADS)

Vatanparast, Maryam; Vullum, Per Erik; Nord, Magnus; Zuo, Jian-Min; Reenaas, Turid W.; Holmestad, Randi

2017-09-01

Geometric phase analysis (GPA), a fast and simple Fourier space method for strain analysis, can give useful information on accumulated strain and defect propagation in multiple layers of semiconductors, including quantum dot materials. In this work, GPA has been applied to high resolution Z-contrast scanning transmission electron microscopy (STEM) images. Strain maps determined from different g vectors of these images are compared to each other, in order to analyze and assess the GPA technique in terms of accuracy. The SmartAlign tool has been used to improve the STEM image quality getting more reliable results. Strain maps from template matching as a real space approach are compared with strain maps from GPA, and it is discussed that a real space analysis is a better approach than GPA for aberration corrected STEM images.

Joint Multi-Leaf Segmentation, Alignment, and Tracking for Fluorescence Plant Videos.

PubMed

Yin, Xi; Liu, Xiaoming; Chen, Jin; Kramer, David M

2018-06-01

This paper proposes a novel framework for fluorescence plant video processing. The plant research community is interested in the leaf-level photosynthetic analysis within a plant. A prerequisite for such analysis is to segment all leaves, estimate their structures, and track them over time. We identify this as a joint multi-leaf segmentation, alignment, and tracking problem. First, leaf segmentation and alignment are applied on the last frame of a plant video to find a number of well-aligned leaf candidates. Second, leaf tracking is applied on the remaining frames with leaf candidate transformation from the previous frame. We form two optimization problems with shared terms in their objective functions for leaf alignment and tracking respectively. A quantitative evaluation framework is formulated to evaluate the performance of our algorithm with four metrics. Two models are learned to predict the alignment accuracy and detect tracking failure respectively in order to provide guidance for subsequent plant biology analysis. The limitation of our algorithm is also studied. Experimental results show the effectiveness, efficiency, and robustness of the proposed method.

Laser-assisted atom probe tomography of four paired poly-Si/SiO2 multiple-stacks with each thickness of 10 nm

NASA Astrophysics Data System (ADS)

Kwak, C.-M.; Seol, J.-B.; Kim, Y.-T.; Park, C.-G.

2017-02-01

For the past 10 years, laser-assisted atom probe tomography (APT) analysis has been performed to quantify the near-atomic scale distribution of elements and their local chemical compositions within interfaces that determine the design, processing, and properties of virtually all materials. However, the nature of the occurring laser-induced emission at the surface of needle-shaped sample is highly complex and it has been an ongoing challenge to understand the surface-related interactions between laser-sources and tips containing non-conductive oxides for a robust and reliable analysis of multiple-stacked devices. Here, we find that the APT analysis of four paired poly-Si/SiO2 (conductive/non-conductive) multiple stacks with each thickness of 10 nm is governed by experimentally monitoring three experimental conditions, such as laser-beam energies ranged from 30 to 200 nJ, analysis temperatures varying with 30-100 K, and the inclination of aligned interfaces within a given tip toward analysis direction. Varying with laser-energy and analysis temperature, a drastic compositional ratio of doubly charged Si ions to single charged Si ions within conductive poly-Si layers is modified, as compared with ones detected in the non-conductive layers. Severe distorted APT images of multiple stacks are also inevitable, especially at the conductive layers, and leading to a lowering of the successful analysis yields. This lower throughput has been overcome though changing the inclination of interfaces within a given tip to analysis direction (planar interfaces parallel to the tip axis), but significant deviations in chemical compositions of a conductive layer counted from those of tips containing planar interfaces perpendicular to the tip axis are unavoidable owing to the Si2, SiH2O, and Si2O ions detected, for the first time, within poly-Si layers.

DNA barcoding the native flowering plants and conifers of Wales.

PubMed

de Vere, Natasha; Rich, Tim C G; Ford, Col R; Trinder, Sarah A; Long, Charlotte; Moore, Chris W; Satterthwaite, Danielle; Davies, Helena; Allainguillaume, Joel; Ronca, Sandra; Tatarinova, Tatiana; Garbett, Hannah; Walker, Kevin; Wilkinson, Mike J

2012-01-01

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification.

DNA Barcoding the Native Flowering Plants and Conifers of Wales

PubMed Central

de Vere, Natasha; Rich, Tim C. G.; Ford, Col R.; Trinder, Sarah A.; Long, Charlotte; Moore, Chris W.; Satterthwaite, Danielle; Davies, Helena; Allainguillaume, Joel; Ronca, Sandra; Tatarinova, Tatiana; Garbett, Hannah; Walker, Kevin; Wilkinson, Mike J.

2012-01-01

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification. PMID:22701588

Four-probe charge transport measurements on individual vertically aligned carbon nanofibers

NASA Astrophysics Data System (ADS)

Zhang, Lan; Austin, Derek; Merkulov, Vladimir I.; Meleshko, Anatoli V.; Klein, Kate L.; Guillorn, Michael A.; Lowndes, Douglas H.; Simpson, Michael L.

2004-05-01

We report four-probe I-V measurements on individual vertically aligned carbon nanofibers (VACNFs). These measurements were enabled by the fabrication of multiple Ti/Au ohmic contacts on individual fibers that exhibited resistance of only a few kilohms. These measurements demonstrate that VACNFs exhibit linear I-V behavior at room temperature, with a resistivity of approximately 4.2×10-3 Ω cm. Our measurements are consistent with a dominant transport mechanism of electrons traveling through intergraphitic planes in the VACNFs.

Flavivirus and Filovirus EvoPrinters: New alignment tools for the comparative analysis of viral evolution.

PubMed

Brody, Thomas; Yavatkar, Amarendra S; Park, Dong Sun; Kuzin, Alexander; Ross, Jermaine; Odenwald, Ward F

2017-06-01

Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest. We have adapted EvoPrinter alignment algorithms for the rapid comparative analysis of Flavivirus or Filovirus sequences including Zika and Ebola strains. The user can input a full genome or partial viral sequence and then view either individual comparisons or generate color-coded readouts that superimpose hundreds of one-on-one alignments to identify unique or shared identity SNPs that reveal ancestral relationships between strains. The user can also opt to select a database genome in order to access a library of pre-aligned genomes of either 1,094 Flaviviruses or 460 Filoviruses for rapid comparative analysis with all database entries or a select subset. Using EvoPrinter search and alignment programs, we show the following: 1) superimposing alignment data from many related strains identifies lineage identity SNPs, which enable the assessment of sublineage complexity within viral outbreaks; 2) whole-genome SNP profile screens uncover novel Dengue2 and Zika recombinant strains and their parental lineages; 3) differential SNP profiling identifies host cell A-to-I hyper-editing within Ebola and Marburg viruses, and 4) hundreds of superimposed one-on-one Ebola genome alignments highlight ultra-conserved regulatory sequences, invariant amino acid codons and evolutionarily variable protein-encoding domains within a single genome. EvoPrinter allows for the assessment of lineage complexity within Flavivirus or Filovirus outbreaks, identification of recombinant strains, highlights sequences that have undergone host cell A-to-I editing, and identifies unique input and database SNPs within highly conserved sequences. EvoPrinter's ability to superimpose alignment data from hundreds of strains onto a single genome has allowed us to identify unique Zika virus sublineages that are currently spreading in South, Central and North America, the Caribbean, and in China. This new set of integrated alignment programs should serve as a useful addition to existing tools for the comparative analysis of these viruses.

An Analysis of the Alignment of the Grade 12 Physical Sciences Examination and the Core Curriculum in South Africa

ERIC Educational Resources Information Center

Edwards, Nazeem

2010-01-01

I report on an analysis of the alignment between the South African Grade 12 Physical Sciences core curriculum content and the exemplar papers of 2008, and the final examination papers of 2008 and 2009. A two-dimensional table was used for both the curriculum and the examination in order to calculate the Porter alignment index, which indicates the…

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

PubMed

Zemla, Adam T; Lang, Dorothy M; Kostova, Tanya; Andino, Raul; Ecale Zhou, Carol L

2011-06-02

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

Comparative sequence analysis of acid sensitive/resistance proteins in Escherichia coli and Shigella flexneri

PubMed Central

Manikandan, Selvaraj; Balaji, Seetharaaman; Kumar, Anil; Kumar, Rita

2007-01-01

The molecular basis for the survival of bacteria under extreme conditions in which growth is inhibited is a question of great current interest. A preliminary study was carried out to determine residue pattern conservation among the antiporters of enteric bacteria, responsible for extreme acid sensitivity especially in Escherichia coli and Shigella flexneri. Here we found the molecular evidence that proved the relationship between E. coli and S. flexneri. Multiple sequence alignment of the gadC coded acid sensitive antiporter showed many conserved residue patterns at regular intervals at the N-terminal region. It was observed that as the alignment approaches towards the C-terminal, the number of conserved residues decreases, indicating that the N-terminal region of this protein has much active role when compared to the carboxyl terminal. The motif, FHLVFFLLLGG, is well conserved within the entire gadC coded protein at the amino terminal. The motif is also partially conserved among other antiporters (which are not coded by gadC) but involved in acid sensitive/resistance mechanism. Phylogenetic cluster analysis proves the relationship of Escherichia coli and Shigella flexneri. The gadC coded proteins are converged as a clade and diverged from other antiporters belongs to the amino acid-polyamine-organocation (APC) superfamily. PMID:21670792

Integrating alternative splicing detection into gene prediction.

PubMed

Foissac, Sylvain; Schiex, Thomas

2005-02-10

Alternative splicing (AS) is now considered as a major actor in transcriptome/proteome diversity and it cannot be neglected in the annotation process of a new genome. Despite considerable progresses in term of accuracy in computational gene prediction, the ability to reliably predict AS variants when there is local experimental evidence of it remains an open challenge for gene finders. We have used a new integrative approach that allows to incorporate AS detection into ab initio gene prediction. This method relies on the analysis of genomically aligned transcript sequences (ESTs and/or cDNAs), and has been implemented in the dynamic programming algorithm of the graph-based gene finder EuGENE. Given a genomic sequence and a set of aligned transcripts, this new version identifies the set of transcripts carrying evidence of alternative splicing events, and provides, in addition to the classical optimal gene prediction, alternative optimal predictions (among those which are consistent with the AS events detected). This allows for multiple annotations of a single gene in a way such that each predicted variant is supported by a transcript evidence (but not necessarily with a full-length coverage). This automatic combination of experimental data analysis and ab initio gene finding offers an ideal integration of alternatively spliced gene prediction inside a single annotation pipeline.

A machine-learning approach reveals that alignment properties alone can accurately predict inference of lateral gene transfer from discordant phylogenies.

PubMed

Roettger, Mayo; Martin, William; Dagan, Tal

2009-09-01

Among the methods currently used in phylogenomic practice to detect the presence of lateral gene transfer (LGT), one of the most frequently employed is the comparison of gene tree topologies for different genes. In cases where the phylogenies for different genes are incompatible, or discordant, for well-supported branches there are three simple interpretations for the result: 1) gene duplications (paralogy) followed by many independent gene losses have occurred, 2) LGT has occurred, or 3) the phylogeny is well supported but for reasons unknown is nonetheless incorrect. Here, we focus on the third possibility by examining the properties of 22,437 published multiple sequence alignments, the Bayesian maximum likelihood trees for which either do or do not suggest the occurrence of LGT by the criterion of discordant branches. The alignments that produce discordant phylogenies differ significantly in several salient alignment properties from those that do not. Using a support vector machine, we were able to predict the inference of discordant tree topologies with up to 80% accuracy from alignment properties alone.

Field-aligned currents associated with multiple arc systems

NASA Astrophysics Data System (ADS)

Wu, J.; Knudsen, D. J.; Gillies, D. M.; Donovan, E.; Burchill, J. K.

2016-12-01

It is often thought that auroral arcs are a direct consequence of upward field-aligned currents. In fact, the relation between currents and brightness is more complicated. Multiple auroral arc systems provide and opportunity to study this relation in detail; this information can be used as a test of models for quasi-static arc formation. In this study, we have identified two types of FAC configurations in multiple parallel arc systems using ground-based optical data from the THEMIS all-sky imagers (ASIs), magnetometers and electric field instruments onboard the Swarm satellites during the period from December 2013 to March 2015. In type 1 events, each arc is an intensification within a broad, unipolar current sheet and downward currents only exist outside the upward current sheet. In type 2 events, multiple arc systems represent a collection of multiple up/down current pairs. By collecting 12 events for type 1 and 17 events for type 2, we find that (1) Type 1 events are mainly located between 22-23MLT. Type 2 events are mainly located around midnight. (2) The typical size of upward and downward FAC in type 2 events are comparable, while upward FAC in type 1 events are larger than downward FAC. (3) Upward currents with more arcs embedded have larger intensities and widths. (4) There is no significant difference between the characteristic widths of multiple arcs and single arcs.

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

PubMed Central

Margulies, Elliott H.; Cooper, Gregory M.; Asimenos, George; Thomas, Daryl J.; Dewey, Colin N.; Siepel, Adam; Birney, Ewan; Keefe, Damian; Schwartz, Ariel S.; Hou, Minmei; Taylor, James; Nikolaev, Sergey; Montoya-Burgos, Juan I.; Löytynoja, Ari; Whelan, Simon; Pardi, Fabio; Massingham, Tim; Brown, James B.; Bickel, Peter; Holmes, Ian; Mullikin, James C.; Ureta-Vidal, Abel; Paten, Benedict; Stone, Eric A.; Rosenbloom, Kate R.; Kent, W. James; Bouffard, Gerard G.; Guan, Xiaobin; Hansen, Nancy F.; Idol, Jacquelyn R.; Maduro, Valerie V.B.; Maskeri, Baishali; McDowell, Jennifer C.; Park, Morgan; Thomas, Pamela J.; Young, Alice C.; Blakesley, Robert W.; Muzny, Donna M.; Sodergren, Erica; Wheeler, David A.; Worley, Kim C.; Jiang, Huaiyang; Weinstock, George M.; Gibbs, Richard A.; Graves, Tina; Fulton, Robert; Mardis, Elaine R.; Wilson, Richard K.; Clamp, Michele; Cuff, James; Gnerre, Sante; Jaffe, David B.; Chang, Jean L.; Lindblad-Toh, Kerstin; Lander, Eric S.; Hinrichs, Angie; Trumbower, Heather; Clawson, Hiram; Zweig, Ann; Kuhn, Robert M.; Barber, Galt; Harte, Rachel; Karolchik, Donna; Field, Matthew A.; Moore, Richard A.; Matthewson, Carrie A.; Schein, Jacqueline E.; Marra, Marco A.; Antonarakis, Stylianos E.; Batzoglou, Serafim; Goldman, Nick; Hardison, Ross; Haussler, David; Miller, Webb; Pachter, Lior; Green, Eric D.; Sidow, Arend

2007-01-01

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization. PMID:17567995

GenomeVista

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poliakov, Alexander; Couronne, Olivier

2002-11-04

Aligning large vertebrate genomes that are structurally complex poses a variety of problems not encountered on smaller scales. Such genomes are rich in repetitive elements and contain multiple segmental duplications, which increases the difficulty of identifying true orthologous SNA segments in alignments. The sizes of the sequences make many alignment algorithms designed for comparing single proteins extremely inefficient when processing large genomic intervals. We integrated both local and global alignment tools and developed a suite of programs for automatically aligning large vertebrate genomes and identifying conserved non-coding regions in the alignments. Our method uses the BLAT local alignment program tomore » find anchors on the base genome to identify regions of possible homology for a query sequence. These regions are postprocessed to find the best candidates which are then globally aligned using the AVID global alignment program. In the last step conserved non-coding segments are identified using VISTA. Our methods are fast and the resulting alignments exhibit a high degree of sensitivity, covering more than 90% of known coding exons in the human genome. The GenomeVISTA software is a suite of Perl programs that is built on a MySQL database platform. The scheduler gets control data from the database, builds a queve of jobs, and dispatches them to a PC cluster for execution. The main program, running on each node of the cluster, processes individual sequences. A Perl library acts as an interface between the database and the above programs. The use of a separate library allows the programs to function independently of the database schema. The library also improves on the standard Perl MySQL database interfere package by providing auto-reconnect functionality and improved error handling.« less

BarraCUDA - a fast short read sequence aligner using graphics processing units

PubMed Central

2012-01-01

Background With the maturation of next-generation DNA sequencing (NGS) technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU), extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC) clusters. In this article, we describe the implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings Using the NVIDIA Compute Unified Device Architecture (CUDA) software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http://seqbarracuda.sf.net PMID:22244497

B-MIC: An Ultrafast Three-Level Parallel Sequence Aligner Using MIC.

PubMed

Cui, Yingbo; Liao, Xiangke; Zhu, Xiaoqian; Wang, Bingqiang; Peng, Shaoliang

2016-03-01

Sequence alignment is the central process for sequence analysis, where mapping raw sequencing data to reference genome. The large amount of data generated by NGS is far beyond the process capabilities of existing alignment tools. Consequently, sequence alignment becomes the bottleneck of sequence analysis. Intensive computing power is required to address this challenge. Intel recently announced the MIC coprocessor, which can provide massive computing power. The Tianhe-2 is the world's fastest supercomputer now equipped with three MIC coprocessors each compute node. A key feature of sequence alignment is that different reads are independent. Considering this property, we proposed a MIC-oriented three-level parallelization strategy to speed up BWA, a widely used sequence alignment tool, and developed our ultrafast parallel sequence aligner: B-MIC. B-MIC contains three levels of parallelization: firstly, parallelization of data IO and reads alignment by a three-stage parallel pipeline; secondly, parallelization enabled by MIC coprocessor technology; thirdly, inter-node parallelization implemented by MPI. In this paper, we demonstrate that B-MIC outperforms BWA by a combination of those techniques using Inspur NF5280M server and the Tianhe-2 supercomputer. To the best of our knowledge, B-MIC is the first sequence alignment tool to run on Intel MIC and it can achieve more than fivefold speedup over the original BWA while maintaining the alignment precision.

A Preliminary Investigation into the Added Value of Multiple Gates and Informants in Universal Screening for Behavioral and Emotional Risk

ERIC Educational Resources Information Center

Dowdy, Erin; Dever, Bridget V.; Raines, Tara C.; Moffa, Kathryn

2016-01-01

Mental health screening in schools is a progressive practice to identify students for prevention and intervention services. Multiple gating procedures, in which students are provided more intensive assessments following initial identification of risk, are aligned with prevention science and poised to enhance multi-tiered systems of support. Yet,…

Universal primers for amplification of the complete mitochondrial control region in marine fish species.

PubMed

Cheng, Y Z; Xu, T J; Jin, X X; Tang, D; Wei, T; Sun, Y Y; Meng, F Q; Shi, G; Wang, R X

2012-01-01

Through multiple alignment analysis of mitochondrial tRNA-Thr and tRNA-Phe sequences from 161 fishes, new universal primers specially targeting the entire mitochondrial control region were designed. This new primer set successfully amplified the expected PCR products from various kinds of marine fish species, belonging to various families, and the amplified segments were confirmed to be the control region by sequencing. These primers provide a useful tool to study the control region diversity in economically important fish species, the possible mechanism of control region evolution, and the functions of the conserved motifs in the control region.

Evol and ProDy for bridging protein sequence evolution and structural dynamics

PubMed Central

Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R.; Bahar, Ivet

2014-01-01

Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. Availability and implementation: ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. Contact: bahar@pitt.edu PMID:24849577

[Challenges of the right to health in the Colombian model].

PubMed

Bernal, Oscar; Barbosa, Samuel

2015-01-01

Health in Colombia is now a fundamental right that has to be provided and protected by the government. We evaluated the strengths and difficulties of the health system with respect to the statutory law enacted in February 2015, using methodologies for analysis of health systems proposed by the WHO and the World Bank. The challenges include the fragmentation and specialization of services, access barriers and incentives that are not aligned with the quality, weak governance, multiple actors with little coordination and information system that does not measure results. The government needs to find a necessary social agreement, a balance between the particular and the collective benefit.

Discovery and analysis of an active long terminal repeat-retrotransposable element in Aspergillus oryzae.

PubMed

Jie Jin, Feng; Hara, Seiichi; Sato, Atsushi; Koyama, Yasuji

2014-01-01

Wild-type Aspergillus oryzae RIB40 contains two copies of the AO090005001597 gene. We previously constructed A. oryzae RIB40 strain, RKuAF8B, with multiple chromosomal deletions, in which the AO090005001597 copy number was found to be increased significantly. Sequence analysis indicated that AO090005001597 is part of a putative 6,000-bp retrotransposable element, flanked by two long terminal repeats (LTRs) of 669 bp, with characteristics of retroviruses and retrotransposons, and thus designated AoLTR (A. oryzae LTR-retrotransposable element). AoLTR comprised putative reverse transcriptase, RNase H, and integrase domains. The deduced amino acid sequence alignment of AoLTR showed 94% overall identity with AFLAV, an A. flavus Tf1/sushi retrotransposon. Quantitative real-time RT-PCR showed that AoLTR gene expression was significantly increased in the RKuAF8B, in accordance with the increased copy number. Inverse PCR indicated that the full-length retrotransposable element was randomly integrated into multiple genomic locations. However, no obvious phenotypic changes were associated with the increased AoLTR gene copy number.

Molecular Cloning and Sequence Analysis of a Phenylalanine Ammonia-Lyase Gene from Dendrobium

PubMed Central

Cai, Yongping; Lin, Yi

2013-01-01

In this study, a phenylalanine ammonia-lyase (PAL) gene was cloned from Dendrobium candidum using homology cloning and RACE. The full-length sequence and catalytic active sites that appear in PAL proteins of Arabidopsis thaliana and Nicotiana tabacum are also found: PAL cDNA of D. candidum (designated Dc-PAL1, GenBank No. JQ765748) has 2,458 bps and contains a complete open reading frame (ORF) of 2,142 bps, which encodes 713 amino acid residues. The amino acid sequence of DcPAL1 has more than 80% sequence identity with the PAL genes of other plants, as indicated by multiple alignments. The dominant sites and catalytic active sites, which are similar to that showing in PAL proteins of Arabidopsis thaliana and Nicotiana tabacum, are also found in DcPAL1. Phylogenetic tree analysis revealed that DcPAL is more closely related to PALs from orchidaceae plants than to those of other plants. The differential expression patterns of PAL in protocorm-like body, leaf, stem, and root, suggest that the PAL gene performs multiple physiological functions in Dendrobium candidum. PMID:23638048

Modeling of field-aligned guided echoes in the plasmasphere

NASA Astrophysics Data System (ADS)

Fung, Shing F.; Green, James L.

2005-01-01

Ray tracing modeling is used to investigate the plasma conditions under which high-frequency (f ≫ fuh) extraordinary mode waves can be guided along geomagnetic field lines. These guided signals have often been observed as long-range discrete echoes in the plasmasphere by the Radio Plasma Imager (RPI) onboard the Imager for Magnetopause-to-Aurora Global Exploration satellite. Field-aligned discrete echoes are most commonly observed by RPI in the plasmasphere, although they are also observed over the polar cap region. The plasmasphere field-aligned echoes appearing as multiple echo traces at different virtual ranges are attributed to signals reflected successively between conjugate hemispheres that propagate along or nearly along closed geomagnetic field lines. The ray tracing simulations show that field-aligned ducts with as little as 1% density perturbations (depletions) and <10 wavelengths wide can guide nearly field-aligned propagating high-frequency X mode waves. Effective guidance of a wave at a given frequency and wave normal angle (Ψ) depends on the cross-field density scale of the duct, such that ducts with stronger density depletions need to be wider in order to maintain the same gradient of refractive index across the magnetic field. While signal guidance by field aligned density gradient without ducting is possible only over the polar region, conjugate field-aligned echoes that have traversed through the equatorial region are most likely guided by ducting.

Optical properties of orthodontic aligners--spectrophotometry analysis of three types before and after aging.

PubMed

Lombardo, Luca; Arreghini, Angela; Maccarrone, Roberta; Bianchi, Anna; Scalia, Santo; Siciliani, Giuseppe

2015-01-01

The aim was to assess and compare absorbance and transmittance values of three types of clear orthodontic aligners before and after two cycles of in vitro aging. Nine samples of orthodontic aligners from three different manufacturers (Invisalign, Align Technology, Santa Clara, CA, USA; All-In, Micerium, Avegno, GE, Italy; F22 Aligner, Sweden & Martina, Due Carrare, PD, Italy) were selected, and each sample was subjected to spectrophotometry analysis of both its transmittance and absorbance a total of 27 times. Samples were subsequently aged in vitro at a constant temperature in artificial saliva supplemented with food colouring for two cycles of 14 days each. The spectrophotometry protocol was then repeated, and the resulting data were analysed and compared by means of ANOVA (p < 0.05). All types of aligners tested yielded lower transmittance and higher absorbance values after aging, but the difference was not significant in any case. That being said, the F22 aligners were found to be most transparent, both before and after aging, followed by Invisalign and All-In, and these differences were statistically significant. Commercial aligners possess significantly different optical, and therefore aesthetic, properties, both as delivered and following aging.

Analyzing and synthesizing phylogenies using tree alignment graphs.

PubMed

Smith, Stephen A; Brown, Joseph W; Hinchliff, Cody E

2013-01-01

Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG). The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees), we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to observe.

Analyzing and Synthesizing Phylogenies Using Tree Alignment Graphs

PubMed Central

Smith, Stephen A.; Brown, Joseph W.; Hinchliff, Cody E.

2013-01-01

Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG). The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees), we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to observe. PMID:24086118

Multi-Beam Approach for Accelerating Alignment and Calibration of HyspIRI-Like Imaging Spectrometers

NASA Technical Reports Server (NTRS)

Eastwood, Michael L.; Green, Robert O.; Mouroulis, Pantazis; Hochberg, Eric B.; Hein, Randall C.; Kroll, Linley A.; Geier, Sven; Coles, James B.; Meehan, Riley

2012-01-01

A paper describes an optical stimulus that produces more consistent results, and can be automated for unattended, routine generation of data analysis products needed by the integration and testing team assembling a high-fidelity imaging spectrometer system. One key attribute of the system is an arrangement of pick-off mirrors that provides multiple input beams (five in this implementation) to simultaneously provide stimulus light to several field angles along the field of view of the sensor under test, allowing one data set to contain all the information that previously required five data sets to be separately collected. This stimulus can also be fed by quickly reconfigured sources that ultimately provide three data set types that would previously be collected separately using three different setups: Spectral Response Function (SRF), Cross-track Response Function (CRF), and Along-track Response Function (ARF), respectively. This method also lends itself to expansion of the number of field points if less interpolation across the field of view is desirable. An absolute minimum of three is required at the beginning stages of imaging spectrometer alignment.

RNAcode: Robust discrimination of coding and noncoding regions in comparative sequence data

PubMed Central

Washietl, Stefan; Findeiß, Sven; Müller, Stephan A.; Kalkhof, Stefan; von Bergen, Martin; Hofacker, Ivo L.; Stadler, Peter F.; Goldman, Nick

2011-01-01

With the availability of genome-wide transcription data and massive comparative sequencing, the discrimination of coding from noncoding RNAs and the assessment of coding potential in evolutionarily conserved regions arose as a core analysis task. Here we present RNAcode, a program to detect coding regions in multiple sequence alignments that is optimized for emerging applications not covered by current protein gene-finding software. Our algorithm combines information from nucleotide substitution and gap patterns in a unified framework and also deals with real-life issues such as alignment and sequencing errors. It uses an explicit statistical model with no machine learning component and can therefore be applied “out of the box,” without any training, to data from all domains of life. We describe the RNAcode method and apply it in combination with mass spectrometry experiments to predict and confirm seven novel short peptides in Escherichia coli and to analyze the coding potential of RNAs previously annotated as “noncoding.” RNAcode is open source software and available for all major platforms at http://wash.github.com/rnacode. PMID:21357752

RNAcode: robust discrimination of coding and noncoding regions in comparative sequence data.

PubMed

Washietl, Stefan; Findeiss, Sven; Müller, Stephan A; Kalkhof, Stefan; von Bergen, Martin; Hofacker, Ivo L; Stadler, Peter F; Goldman, Nick

2011-04-01

With the availability of genome-wide transcription data and massive comparative sequencing, the discrimination of coding from noncoding RNAs and the assessment of coding potential in evolutionarily conserved regions arose as a core analysis task. Here we present RNAcode, a program to detect coding regions in multiple sequence alignments that is optimized for emerging applications not covered by current protein gene-finding software. Our algorithm combines information from nucleotide substitution and gap patterns in a unified framework and also deals with real-life issues such as alignment and sequencing errors. It uses an explicit statistical model with no machine learning component and can therefore be applied "out of the box," without any training, to data from all domains of life. We describe the RNAcode method and apply it in combination with mass spectrometry experiments to predict and confirm seven novel short peptides in Escherichia coli and to analyze the coding potential of RNAs previously annotated as "noncoding." RNAcode is open source software and available for all major platforms at http://wash.github.com/rnacode.

Identifying functionally informative evolutionary sequence profiles.

PubMed

Gil, Nelson; Fiser, Andras

2018-04-15

Multiple sequence alignments (MSAs) can provide essential input to many bioinformatics applications, including protein structure prediction and functional annotation. However, the optimal selection of sequences to obtain biologically informative MSAs for such purposes is poorly explored, and has traditionally been performed manually. We present Selection of Alignment by Maximal Mutual Information (SAMMI), an automated, sequence-based approach to objectively select an optimal MSA from a large set of alternatives sampled from a general sequence database search. The hypothesis of this approach is that the mutual information among MSA columns will be maximal for those MSAs that contain the most diverse set possible of the most structurally and functionally homogeneous protein sequences. SAMMI was tested to select MSAs for functional site residue prediction by analysis of conservation patterns on a set of 435 proteins obtained from protein-ligand (peptides, nucleic acids and small substrates) and protein-protein interaction databases. Availability and implementation: A freely accessible program, including source code, implementing SAMMI is available at https://github.com/nelsongil92/SAMMI.git. andras.fiser@einstein.yu.edu. Supplementary data are available at Bioinformatics online.

Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach.

PubMed

Andreatta, Massimo; Lund, Ole; Nielsen, Morten

2013-01-01

Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides. The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities in peptide data by performing two essential tasks simultaneously: alignment and clustering of peptide data. We apply the method to de-convolute binding motifs in a panel of peptide datasets with different degrees of complexity spanning from the simplest case of pre-aligned fixed-length peptides to cases of unaligned peptide datasets of variable length. Example applications described in this article include mixtures of binders to different MHC class I and class II alleles, distinct classes of ligands for SH3 domains and sub-specificities of the HLA-A*02:01 molecule. The Gibbs clustering method is available online as a web server at http://www.cbs.dtu.dk/services/GibbsCluster.

MSAProbs-MPI: parallel multiple sequence aligner for distributed-memory systems.

PubMed

González-Domínguez, Jorge; Liu, Yongchao; Touriño, Juan; Schmidt, Bertil

2016-12-15

MSAProbs is a state-of-the-art protein multiple sequence alignment tool based on hidden Markov models. It can achieve high alignment accuracy at the expense of relatively long runtimes for large-scale input datasets. In this work we present MSAProbs-MPI, a distributed-memory parallel version of the multithreaded MSAProbs tool that is able to reduce runtimes by exploiting the compute capabilities of common multicore CPU clusters. Our performance evaluation on a cluster with 32 nodes (each containing two Intel Haswell processors) shows reductions in execution time of over one order of magnitude for typical input datasets. Furthermore, MSAProbs-MPI using eight nodes is faster than the GPU-accelerated QuickProbs running on a Tesla K20. Another strong point is that MSAProbs-MPI can deal with large datasets for which MSAProbs and QuickProbs might fail due to time and memory constraints, respectively. Source code in C ++ and MPI running on Linux systems as well as a reference manual are available at http://msaprobs.sourceforge.net CONTACT: jgonzalezd@udc.esSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CodonLogo: a sequence logo-based viewer for codon patterns.

PubMed

Sharma, Virag; Murphy, David P; Provan, Gregory; Baranov, Pavel V

2012-07-15

Conserved patterns across a multiple sequence alignment can be visualized by generating sequence logos. Sequence logos show each column in the alignment as stacks of symbol(s) where the height of a stack is proportional to its informational content, whereas the height of each symbol within the stack is proportional to its frequency in the column. Sequence logos use symbols of either nucleotide or amino acid alphabets. However, certain regulatory signals in messenger RNA (mRNA) act as combinations of codons. Yet no tool is available for visualization of conserved codon patterns. We present the first application which allows visualization of conserved regions in a multiple sequence alignment in the context of codons. CodonLogo is based on WebLogo3 and uses the same heuristics but treats codons as inseparable units of a 64-letter alphabet. CodonLogo can discriminate patterns of codon conservation from patterns of nucleotide conservation that appear indistinguishable in standard sequence logos. The CodonLogo source code and its implementation (in a local version of the Galaxy Browser) are available at http://recode.ucc.ie/CodonLogo and through the Galaxy Tool Shed at http://toolshed.g2.bx.psu.edu/.

JavaScript DNA translator: DNA-aligned protein translations.

PubMed

Perry, William L

2002-12-01

There are many instances in molecular biology when it is necessary to identify ORFs in a DNA sequence. While programs exist for displaying protein translations in multiple ORFs in alignment with a DNA sequence, they are often expensive, exist as add-ons to software that must be purchased, or are only compatible with a particular operating system. JavaScript DNA Translator is a shareware application written in JavaScript, a scripting language interpreted by the Netscape Communicator and Internet Explorer Web browsers, which makes it compatible with several different operating systems. While the program uses a familiar Web page interface, it requires no connection to the Internet since calculations are performed on the user's own computer. The program analyzes one or multiple DNA sequences and generates translations in up to six reading frames aligned to a DNA sequence, in addition to displaying translations as separate sequences in FASTA format. ORFs within a reading frame can also be displayed as separate sequences. Flexible formatting options are provided, including the ability to hide ORFs below a minimum size specified by the user. The program is available free of charge at the BioTechniques Software Library (www.Biotechniques.com).

LC-MS Data Processing with MAVEN: A Metabolomic Analysis and Visualization Engine

PubMed Central

Clasquin, Michelle F.; Melamud, Eugene; Rabinowitz, Joshua D.

2014-01-01

MAVEN is an open-source software program for interactive processing of LC-MS-based metabolomics data. MAVEN enables rapid and reliable metabolite quantitation from multiple reaction monitoring data or high-resolution full-scan mass spectrometry data. It automatically detects and reports peak intensities for isotope-labeled metabolites. Menu-driven, click-based navigation allows visualization of raw and analyzed data. Here we provide a User Guide for MAVEN. Step-by-step instructions are provided for data import, peak alignment across samples, identification of metabolites that differ strongly between biological conditions, quantitation and visualization of isotope-labeling patterns, and export of tables of metabolite-specific peak intensities. Together, these instructions describe a workflow that allows efficient processing of raw LC-MS data into a form ready for biological analysis. PMID:22389014

LC-MS data processing with MAVEN: a metabolomic analysis and visualization engine.

PubMed

Clasquin, Michelle F; Melamud, Eugene; Rabinowitz, Joshua D

2012-03-01

MAVEN is an open-source software program for interactive processing of LC-MS-based metabolomics data. MAVEN enables rapid and reliable metabolite quantitation from multiple reaction monitoring data or high-resolution full-scan mass spectrometry data. It automatically detects and reports peak intensities for isotope-labeled metabolites. Menu-driven, click-based navigation allows visualization of raw and analyzed data. Here we provide a User Guide for MAVEN. Step-by-step instructions are provided for data import, peak alignment across samples, identification of metabolites that differ strongly between biological conditions, quantitation and visualization of isotope-labeling patterns, and export of tables of metabolite-specific peak intensities. Together, these instructions describe a workflow that allows efficient processing of raw LC-MS data into a form ready for biological analysis.

Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions

NASA Astrophysics Data System (ADS)

Chaudhari, Rajan; Heim, Andrew J.; Li, Zhijun

2015-05-01

Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.

RBT-GA: a novel metaheuristic for solving the Multiple Sequence Alignment problem.

PubMed

Taheri, Javid; Zomaya, Albert Y

2009-07-07

Multiple Sequence Alignment (MSA) has always been an active area of research in Bioinformatics. MSA is mainly focused on discovering biologically meaningful relationships among different sequences or proteins in order to investigate the underlying main characteristics/functions. This information is also used to generate phylogenetic trees. This paper presents a novel approach, namely RBT-GA, to solve the MSA problem using a hybrid solution methodology combining the Rubber Band Technique (RBT) and the Genetic Algorithm (GA) metaheuristic. RBT is inspired by the behavior of an elastic Rubber Band (RB) on a plate with several poles, which is analogues to locations in the input sequences that could potentially be biologically related. A GA attempts to mimic the evolutionary processes of life in order to locate optimal solutions in an often very complex landscape. RBT-GA is a population based optimization algorithm designed to find the optimal alignment for a set of input protein sequences. In this novel technique, each alignment answer is modeled as a chromosome consisting of several poles in the RBT framework. These poles resemble locations in the input sequences that are most likely to be correlated and/or biologically related. A GA-based optimization process improves these chromosomes gradually yielding a set of mostly optimal answers for the MSA problem. RBT-GA is tested with one of the well-known benchmarks suites (BALiBASE 2.0) in this area. The obtained results show that the superiority of the proposed technique even in the case of formidable sequences.

3D tissue formation by stacking detachable cell sheets formed on nanofiber mesh.

PubMed

Kim, Min Sung; Lee, Byungjun; Kim, Hong Nam; Bang, Seokyoung; Yang, Hee Seok; Kang, Seong Min; Suh, Kahp-Yang; Park, Suk-Hee; Jeon, Noo Li

2017-03-23

We present a novel approach for assembling 3D tissue by layer-by-layer stacking of cell sheets formed on aligned nanofiber mesh. A rigid frame was used to repeatedly collect aligned electrospun PCL (polycaprolactone) nanofiber to form a mesh structure with average distance between fibers 6.4 µm. When human umbilical vein endothelial cells (HUVECs), human foreskin dermal fibroblasts, and skeletal muscle cells (C2C12) were cultured on the nanofiber mesh, they formed confluent monolayers and could be handled as continuous cell sheets with areas 3 × 3 cm 2 or larger. Thicker 3D tissues have been formed by stacking multiple cell sheets collected on frames that can be nested (i.e. Matryoshka dolls) without any special tools. When cultured on the nanofiber mesh, skeletal muscle, C2C12 cells oriented along the direction of the nanofibers and differentiated into uniaxially aligned multinucleated myotube. Myotube cell sheets were stacked (upto 3 layers) in alternating or aligned directions to form thicker tissue with ∼50 µm thickness. Sandwiching HUVEC cell sheets with two dermal fibroblast cell sheets resulted in vascularized 3D tissue. HUVECs formed extensive networks and expressed CD31, a marker of endothelial cells. Cell sheets formed on nanofiber mesh have a number of advantages, including manipulation and stacking of multiple cell sheets for constructing 3D tissue and may find applications in a variety of tissue engineering applications.

Alignment and integration of complex networks by hypergraph-based spectral clustering

NASA Astrophysics Data System (ADS)

Michoel, Tom; Nachtergaele, Bruno

2012-11-01

Complex networks possess a rich, multiscale structure reflecting the dynamical and functional organization of the systems they model. Often there is a need to analyze multiple networks simultaneously, to model a system by more than one type of interaction, or to go beyond simple pairwise interactions, but currently there is a lack of theoretical and computational methods to address these problems. Here we introduce a framework for clustering and community detection in such systems using hypergraph representations. Our main result is a generalization of the Perron-Frobenius theorem from which we derive spectral clustering algorithms for directed and undirected hypergraphs. We illustrate our approach with applications for local and global alignment of protein-protein interaction networks between multiple species, for tripartite community detection in folksonomies, and for detecting clusters of overlapping regulatory pathways in directed networks.

Alignment and integration of complex networks by hypergraph-based spectral clustering.

PubMed

Michoel, Tom; Nachtergaele, Bruno

2012-11-01

Complex networks possess a rich, multiscale structure reflecting the dynamical and functional organization of the systems they model. Often there is a need to analyze multiple networks simultaneously, to model a system by more than one type of interaction, or to go beyond simple pairwise interactions, but currently there is a lack of theoretical and computational methods to address these problems. Here we introduce a framework for clustering and community detection in such systems using hypergraph representations. Our main result is a generalization of the Perron-Frobenius theorem from which we derive spectral clustering algorithms for directed and undirected hypergraphs. We illustrate our approach with applications for local and global alignment of protein-protein interaction networks between multiple species, for tripartite community detection in folksonomies, and for detecting clusters of overlapping regulatory pathways in directed networks.

Self-assembly of vertically aligned quantum ring-dot structure by Multiple Droplet Epitaxy

NASA Astrophysics Data System (ADS)

Elborg, Martin; Noda, Takeshi; Mano, Takaaki; Kuroda, Takashi; Yao, Yuanzhao; Sakuma, Yoshiki; Sakoda, Kazuaki

2017-11-01

We successfully grow vertically aligned quantum ring-dot structures by Multiple Droplet Epitaxy technique. The growth is achieved by depositing GaAs quantum rings in a first droplet epitaxy process which are subsequently covered by a thin AlGaAs barrier. In a second droplet epitaxy process, Ga droplets preferentially position in the center indentation of the ring as well as attached to the edge of the ring in [ 1 1 bar 0 ] direction. By designing the ring geometry, full selectivity for the center position of the ring is achieved where we crystallize the droplets into quantum dots. The geometry of the ring and dot as well as barrier layer can be controlled in separate growth steps. This technique offers great potential for creating complex quantum molecules for novel quantum information technologies.