bluuebunny/crossref_metadata_2025 huggingface dataset:
GeneAnnot: comprehensive two-way linking between oligonucleotide array probesets and GeneCards genes
Authors: Chalifa-Caspi Vered , Yanai Itai , Ophir Ron , Rosen Naomi , Shmoish Michael , Benjamin-Rodrig Hila , Shklar Maxim , Stein Tsippi Iny , Shmueli Orit , Safran Marilyn , Lancet Doron
Published: March 2004

Motivation: High density oligonucleotide arrays are usually annotated in a one-to-one fashion, with each probeset assigned to one gene. However, in reality, subsets of oligonucleotides in a probeset may match sequences within more than one gene, potentially leading to misinterpretations. Moreover, a gene is often represented by more than one probeset, and analyzing probe matches at the mRNA level can help one deduce whether these probesets are derived from the same or different splice variants.

Results: The GeneAnnot system comprehensively documents the many-to-many relationship between oligonucleotide array probesets and annotated genes in GeneCards™. It performs pairwise alignments between the probe sequences and gene transcripts, and assigns sensitivity and specificity scores to each probeset/gene pair.

Availability:  http://genecards.weizmann.ac.il/geneannot/

Supplementary information: Program description and statistics http://genecards.weizmann.ac.il/geneannot/DOC/index.html
RAG: RNA-As-Graphs database—concepts, analysis, and features
Authors: Gan Hin Hark , Fera Daniela , Zorn Julie , Shiffeldrim Nahum , Tang Michael , Laserson Uri , Kim Namhee , Schlick Tamar
Published: March 2004

Motivation: Understanding RNA's structural diversity is vital for identifying novel RNA structures and pursuing RNA genomics initiatives. By classifying RNA secondary motifs based on correlations between conserved RNA secondary structures and functional properties, we offer an avenue for predicting novel motifs. Although several RNA databases exist, no comprehensive schemes are available for cataloguing the range and diversity of RNA's structural repertoire.

Results: Our RNA-As-Graphs (RAG) database describes and ranks all mathematically possible (including existing and candidate) RNA secondary motifs on the basis of graphical enumeration techniques. We represent RNA secondary structures as two-dimensional graphs (networks), specifying the connectivity between RNA secondary structural elements, such as loops, bulges, stems and junctions. We archive RNA tree motifs as ‘tree graphs’ and other RNAs, including pseudoknots, as general ‘dual graphs’. All RNA motifs are catalogued by graph vertex number (a measure of sequence length) and ranked by topological complexity. The RAG inventory immediately suggests candidates for novel RNA motifs, either naturally occurring or synthetic, and thereby might stimulate the prediction and design of novel RNA motifs.

Availability: The database is accessible on the web at http://monod.biomath.nyu.edu/rna
Automatic prediction of protein domains from sequence information using a hybrid learning system
Authors: Nagarajan Niranjan , Yona Golan
Published: March 2004

Motivation: We describe a novel method for detecting the domain structure of a protein from sequence information alone. The method is based on analyzing multiple sequence alignments that are derived from a database search. Multiple measures are defined to quantify the domain information content of each position along the sequence and are combined into a single predictor using a neural network. The output is further smoothed and post-processed using a probabilistic model to predict the most likely transition positions between domains.

Results: The method was assessed using the domain definitions in SCOP and CATH for proteins of known structure and was compared with several other existing methods. Our method performs well both in terms of accuracy and sensitivity. It improves significantly over the best methods available, even some of the semi-manual ones, while being fully automatic. Our method can also be used to suggest and verify domain partitions based on structural data. A few examples of predicted domain definitions and alternative partitions, as suggested by our method, are also discussed.

Availability: An online domain-prediction server is available at http://biozon.org/tools/domains/
ACID: a database for microarray clone information
Authors: Ringnér Markus , Veerla Srinivas , Andersson Samuel , Staaf Johan , Häkkinen Jari
Published: March 2004

Summary: Array Close Information Database is an online database for information about microarray cDNA clones. For each clone, the database contents include assigned UniGene cluster(s), location in the full-length transcript, assigned gene ontology terms and position in the genome assembly.

Availability:  http://bioinfo.thep.lu.se/acid.html
A comparison of scoring functions for protein sequence profile alignment
Authors: Edgar Robert C. , Sjölander Kimmen
Published: March 2004

Motivation:In recent years, several methods have been proposed for aligning two protein sequence profiles, with reported improvements in alignment accuracy and homolog discrimination versus sequence–sequence methods (e.g. BLAST) and profile–sequence methods (e.g. PSI-BLAST). Profile–profile alignment is also the iterated step in progressive multiple sequence alignment algorithms such as CLUSTALW. However, little is known about the relative performance of different profile–profile scoring functions. In this work, we evaluate the alignment accuracy of 23 different profile–profile scoring functions by comparing alignments of 488 pairs of sequences with identity ≤30% against structural alignments. We optimize parameters for all scoring functions on the same training set and use profiles of alignments from both PSI-BLAST and SAM-T99. Structural alignments are constructed from a consensus between the FSSP database and CE structural aligner. We compare the results with sequence–sequence and sequence–profile methods, including BLAST and PSI-BLAST.

Results: We find that profile–profile alignment gives an average improvement over our test set of typically 2–3% over profile–sequence alignment and ∼40% over sequence–sequence alignment. No statistically significant difference is seen in the relative performance of most of the scoring functions tested. Significantly better results are obtained with profiles constructed from SAM-T99 alignments than from PSI-BLAST alignments.

Availability: Source code, reference alignments and more detailed results are freely available at http://phylogenomics.berkeley.edu/profilealignment/
COACH: profile–profile alignment of protein families using hidden Markov models
Authors: Edgar Robert C. , Sjölander Kimmen
Published: March 2004

Motivation: 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.

Results: 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.

Availability: COACH is freely available from www.drive5.com/lobster
Site2genome: locating short DNA sequences in whole genomes
Authors: Frith Martin C. , Halees Anason S. , Hansen Ulla , Weng Zhiping
Published: March 2004

Summary: Many biological papers describe short, functional DNA sites without specifying their exact positions in the genome. We have developed a Web server that automates the tedious task of locating such sites in eukaryotic genomes, thus giving access to the context of rich annotations that are increasingly available for genome sequences.

Availability:  http://zlab.bu.edu/site2genome/
A hint to search for metalloproteins in gene banks
Authors: Andreini Claudia , Bertini Ivano , Rosato Antonio
Published: March 2004

Motivation: With the advent of genome sequencing, a huge database of protein primary sequences has been accumulating. In parallel, a number of tools to investigate and expand upon this information, e.g. reconstructing and building relationships between protein families and superfamilies, have been developed. Metalloproteins are proteins capable of binding one or more metal ions, which are required for their biological function or for regulation of their activities or for structural purposes. Sometimes, metal binding can be observed in vitro but not be physiologically relevant. At present, there is a lack of specific tools to address the matter of the identification of metalloproteins in databases of gene sequences.

Results: In the present work, an approach exploiting metal-binding patterns (MBPs) of metalloproteins present in the Protein Data Bank to search gene banks for new metalloproteins is presented and applied to copper proteins. Nearly 100 different MBPs have been identified and then used for subsequent applications. The ensemble of sequences of the whole PDB is used to assess the potentiality and limits of the method and to identify levels of confidence for the predictions output by the search. It appears that copper-binding capabilities are identified with a confidence >90% when the percentage of identical amino acids aligned around the MBP by PHI-BLAST is at least 20% with respect to the entire protein domain length. If this percentage is between 10% and 20%, the level of confidence is ∼50%. Application of the methodology to the entire genome sequences of Pyrococcus furiosus, Escherichia coli, Drosophila melanogaster and Homo sapiens suggests some differentiation between prokaryotes and eukaryotes.

Supplementary information: A table reporting statistics on the MBP identified; a list of all hits retrieved for the four organisms considered; a figure showing the number of hits for the four organisms as a function of IdGlobal.
PartiGene—constructing partial genomes
Authors: Parkinson John , Anthony Alasdair , Wasmuth James , Schmid Ralf , Hedley Ann , Blaxter Mark
Published: March 2004

Expressed sequence tags (ESTs) offer a low-cost approach to gene discovery and are being used by an increasing number of laboratories to obtain sequence information for a wide variety of organisms. The challenge lies in processing and organizing this data within a genomic context to facilitate large scale analyses. Here we present PartiGene, an integrated sequence analysis suite that uses freely available public domain software to (1) process raw trace chromatograms into sequence objects suitable for submission to dbEST; (2) place these sequences within a genomic context; (3) perform customizable first-pass annotation of the data; and (4) present the data as HTML tables and an SQL database resource. PartiGene has been used to create a number of non-model organism database resources including NEMBASE (http://www.nematodes.org) and LumbriBase (http://www.earthworms.org/). The packages are readily portable, freely available and can be run on simple Linux-based workstations.

Availability: PartiGene is available from http://www.nematodes.org/PartiGene and also forms part of the EST analysis software, associated with the Natural Environmental Research Council (UK) Bio-Linux project (http://envgen.nox.ac.uk/biolinux.html).
Simple sequence repeat marker loci discovery using SSR primer
Authors: Robinson Andrew J. , Love Christopher G. , Batley Jacqueline , Barker Gary , Edwards David
Published: March 2004

Summary: Simple sequence repeats (SSRs) have become important molecular markers for a broad range of applications, such as genome mapping and characterization, phenotype mapping, marker assisted selection of crop plants and a range of molecular ecology and diversity studies. With the increase in the availability of DNA sequence information, an automated process to identify and design PCR primers for amplification of SSR loci would be a useful tool in plant breeding programs. We report an application that integrates SPUTNIK, an SSR repeat finder, with Primer3, a PCR primer design program, into one pipeline tool, SSR Primer. On submission of multiple FASTA formatted sequences, the script screens each sequence for SSRs using SPUTNIK. The results are parsed to Primer3 for locus-specific primer design. The script makes use of a Web-based interface, enabling remote use.

Availability: This program has been written in PERL and is freely available for non-commercial users by request from the authors. The Web-based version may be accessed at http://hornbill.cspp.latrobe.edu.au/
Align-m—a new algorithm for multiple alignment of highly divergent sequences
Authors: Van Walle Ivo , Lasters Ignace , Wyns Lode
Published: March 2004

Motivation: Multiple alignment of highly divergent sequences is a challenging problem for which available programs tend to show poor performance. Generally, this is due to a scoring function that does not describe biological reality accurately enough or a heuristic that cannot explore solution space efficiently enough. In this respect, we present a new program, Align-m, that uses a non-progressive local approach to guide a global alignment.

Results: Two large test sets were used that represent the entire SCOP classification and cover sequence similarities between 0 and 50% identity. Performance was compared with the publicly available algorithms ClustalW, T-Coffee and DiAlign. In general, Align-m has comparable or slightly higher accuracy in terms of correctly aligned residues, especially for distantly related sequences. Importantly, it aligns much fewer residues incorrectly, with average differences of over 15% compared with some of the other algorithms.

Availability: Align-m and the test sets are available at http://bioinformatics.vub.ac.be
VARAN: a web server for Variability Analysis of DNA microarray experiments
Authors: Golfier G. , Dang M. Tran , Dauphinot L. , Graison E. , Rossier J. , Potier M.-C.
Published: March 2004

Summary: Here, we describe a tool for VARiability Analysis of DNA microarrays experiments (VARAN), a freely available Web server that performs a signal intensity based analysis of the log2 expression ratio variability deduced from DNA microarray data (one or two channels). Two modules are proposed: VARAN generator to compute a sliding windows analysis of the experimental variability (mean and SD) and VARAN analyzer to compare experimental data with an asymptotic variability model previously built with the generator module from control experiments. Both modules provide normalized intensity signals with five possible methods, log ratio values and a list of genes showing significant variations between conditions.

Availability:  http://www.bionet.espci.fr/varan/

Supplementary information:  http://www.bionet.espci.fr/varan/help.html
Evaluation and optimization of clustering in gene expression data analysis
Authors: Famili A. Fazel , Liu Ganming , Liu Ziying
Published: March 2004

Motivation: A measurement of cluster quality is needed to choose potential clusters of genes that contain biologically relevant patterns of gene expression. This is strongly desirable when a large number of gene expression profiles have to be analyzed and proper clusters of genes need to be identified for further analysis, such as the search for meaningful patterns, identification of gene functions or gene response analysis.

Results: We propose a new cluster quality method, called stability, by which unsupervised learning of gene expression data can be performed efficiently. The method takes into account a cluster's stability on partition. We evaluate this method and demonstrate its performance using four independent, real gene expression and three simulated datasets. We demonstrate that our method outperforms other techniques listed in the literature. The method has applications in evaluating clustering validity as well as identifying stable clusters.

Availability: Please contact the first author.
A perturbation-based method for calculating explicit likelihood of evolutionary co-variance in multiple sequence alignments
Authors: Dekker John P. , Fodor Anthony , Aldrich Richard W. , Yellen Gary
Published: March 2004

Motivation: The constituent amino acids of a protein work together to define its structure and to facilitate its function. Their interdependence should be apparent in the evolutionary record of each protein family: positions in the sequence of a protein family that are intimately associated in space or in function should co-vary in evolution. A recent approach by Ranganathan and colleagues proposes to look at subsets of a protein family, selected for their sequence at one position, to see how this affects variation at other positions.

Results: We present a quantitative algorithm for assessing covariation with this approach, based on explicit likelihood calculations. By applying our algorithm to 138 Pfam families with at least one member of known structure, we demonstrate that our method has improved power in finding physically close residues in crystal structures, compared to that of Ranganathan and colleagues.

Supplementary information:  www.afodor.net/bioinfosup.html
A graph theoretical approach for predicting common RNA secondary structure motifs including pseudoknots in unaligned sequences
Authors: Ji Yongmei , Xu Xing , Stormo Gary D.
Published: March 2004

Motivation: RNA structure motifs contained in mRNAs have been found to play important roles in regulating gene expression. However, identification of novel RNA regulatory motifs using computational methods has not been widely explored. Effective tools for predicting novel RNA regulatory motifs based on genomic sequences are needed.

Results: We present a new method for predicting common RNA secondary structure motifs in a set of functionally or evolutionarily related RNA sequences. This method is based on comparison of stems (palindromic helices) between sequences and is implemented by applying graph-theoretical approaches. It first finds all possible stable stems in each sequence and compares stems pairwise between sequences by some defined features to find stems conserved across any two sequences. Then by applying a maximum clique finding algorithm, it finds all significant stems conserved across at least k sequences. Finally, it assembles in topological order all possible compatible conserved stems shared by at least k sequences and reports a number of the best assembled stem sets as the best candidate common structure motifs. This method does not require prior structural alignment of the sequences and is able to detect pseudoknot structures. We have tested this approach on some RNA sequences with known secondary structures, in which it is capable of detecting the real structures completely or partially correctly and outperforms other existing programs for similar purposes.

Availability: The algorithm has been implemented in C++ in a program called comRNA, which is available at http://ural.wustl.edu/softwares.html
Protein secondary structure: entropy, correlations and prediction
Authors: Crooks Gavin E. , Brenner Steven E.
Published: March 2004

Motivation: Is protein secondary structure primarily determined by local interactions between residues closely spaced along the amino acid backbone or by non-local tertiary interactions? To answer this question, we measure the entropy densities of primary and secondary structure sequences, and the local inter-sequence mutual information density.

Results: We find that the important inter-sequence interactions are short ranged, that correlations between neighboring amino acids are essentially uninformative and that only one-fourth of the total information needed to determine the secondary structure is available from local inter-sequence correlations. These observations support the view that the majority of most proteins fold via a cooperative process where secondary and tertiary structure form concurrently. Moreover, existing single-sequence secondary structure prediction algorithms are almost optimal, and we should not expect a dramatic improvement in prediction accuracy.

Availability: Both the data sets and analysis code are freely available from our Web site at http://compbio.berkeley.edu/
Common structural patterns in human genes
Authors: Hill Aubrey , Sorscher Eric
Published: March 2004

Motivation: A graphical representation of the exon–intron structure of various genes, such as that presented by the National Center for Biotechnology Information Map Viewer, suggests a digital waveform or pattern that varies either in amplitude or frequency. This observation suggests that different genes may have portions of their total exon–intron structure in common. The existence of common structural patterns across unrelated genes suggests the repeated insertion of transposable elements throughout the human genome and/or a common structural function.

Results: We compared the exon–intron size patterns of a number of human genes and discovered numerous conserved arrangements with similarity at a high degree of stringency (>99%) across the otherwise unrelated and diverse genomic landscape. In our experimental analyses, more than 200 patterns of length 2 or greater at 99% stringency were found among the 72 genes we compared.
Mathematical characterization of three-dimensional gene expression patterns
Authors: Costa L. da F. , Barbosa M. S. , Manoel E. T. M. , Streicher J. , Müller G. B.
Published: March 2004

Motivation: The importance of a systematic methodology for the mathematical characterization of three-dimensional gene expression patterns in embryonic development.

Methods: By combining lacunarity and multiscale fractal dimension analyses with computer-based methods of three-dimensional reconstruction, it becomes possible to extract new information from in situ hybridization studies. Lacunarity and fractality are appropriate measures for the cloud-like gene activation signals in embryonic tissues. The newly introduced multiscale method provides a natural extension of the fractal dimension concept, being capable of characterizing the fractality of geometrical patterns in terms of spatial scale. This tool can be systematically applied to three-dimensional patterns of gene expression.

Results: Applications are illustrated using the three-dimensional expression patterns of the myogenic marker gene Myf5 in a series of differentiating somites of a mouse embryo.
Development of joint application strategies for two microbial gene finders
Authors: McHardy Alice C. , Goesmann Alexander , Pühler Alfred , Meyer Folker
Published: March 2004

Motivation: As a starting point in annotation of bacterial genomes, gene finding programs are used for the prediction of functional elements in the DNA sequence. Due to the faster pace and increasing number of genome projects currently underway, it is becoming especially important to have performant methods for this task.

Results: This study describes the development of joint application strategies that combine the strengths of two microbial gene finders to improve the overall gene finding performance. Critica is very specific in the detection of similarity-supported genes as it uses a comparative sequence analysis-based approach. Glimmer employs a very sophisticated model of genomic sequence properties and is sensitive also in the detection of organism-specific genes. Based on a data set of 113 microbial genome sequences, we optimized a combined application approach using different parameters with relevance to the gene finding problem. This results in a significant improvement in specificity while there is similarity in sensitivity to Glimmer. The improvement is especially pronounced for GC rich genomes. The method is currently being applied for the annotation of several microbial genomes.

Availability: The methods described have been implemented within the gene prediction component of the GenDB genome annotation system.
GeneCluster 2.0: an advanced toolset for bioarray analysis
Authors: Reich M. , Ohm K. , Angelo M. , Tamayo P. , Mesirov J. P.
Published: March 2004

Summary: GeneCluster 2.0 is a software package for analyzing gene expression and other bioarray data, giving users a variety of methods to build and evaluate class predictors, visualize marker lists, cluster data and validate results. GeneCluster 2.0 greatly expands the data analysis capabilities of GeneCluster 1.0 by adding classification, class discovery and permutation test methods. It includes algorithms for building and testing supervised models using weighted voting and k-nearest neighbor algorithms, a module for systematically finding and evaluating clustering via self-organizing maps, and modules for marker gene selection and heat map visualization that allow users to view and sort samples and genes by many criteria. GeneCluster 2.0 is a standalone Java application and runs on any platform that supports the Java Runtime Environment version 1.3.1 or greater.

Availability:  http://www.broad.mit.edu/cancer/software
Decoupling dynamical systems for pathway identification from metabolic profiles
Authors: Voit Eberhard O. , Almeida Jonas
Published: March 2004

Rationale: Modern molecular biology is generating data of unprecedented quantity and quality. Particularly exciting for biochemical pathway modeling and proteomics are comprehensive, time-dense profiles of metabolites or proteins that are measurable, for instance, with mass spectrometry, nuclear magnetic resonance or protein kinase phosphorylation. These profiles contain a wealth of information about the structure and dynamics of the pathway or network from which the data were obtained. The retrieval of this information requires a combination of computational methods and mathematical models, which are typically represented as systems of ordinary differential equations.

Results: We show that, for the purpose of structure identification, the substitution of differentials with estimated slopes in non-linear network models reduces the coupled system of differential equations to several sets of decoupled algebraic equations, which can be processed efficiently in parallel or sequentially. The estimation of slopes for each time series of the metabolic or proteomic profile is accomplished with a ‘universal function’ that is computed directly from the data by cross-validated training of an artificial neural network (ANN).

Conclusions: Without preprocessing, the inverse problem of determining structure from metabolic or proteomic profile data is challenging and computationally expensive. The combination of system decoupling and data fitting with universal functions simplifies this inverse problem very significantly. Examples show successful estimations and current limitations of the method.

Availability: A preliminary Web-based application for ANN smoothing is accessible at http://bioinformatics.musc.edu/webmetabol/. S-systems can be interactively analyzed with the user-friendly freeware PLAS© (http://correio.cc.fc.ul.pt/~aenf/plas.html) or with the MATLAB module BSTLab (http://bioinformatics.musc.edu/bstlab/), which is currently being beta-tested.
A knowledge-based scale for the analysis and prediction of buried and exposed faces of transmembrane domain proteins
Authors: Beuming Thijs , Weinstein Harel
Published: March 2004

Motivation: The dearth of structural data on α-helical membrane proteins (MPs) has hampered thus far the development of reliable knowledge-based potentials that can be used for automatic prediction of transmembrane (TM) protein structure. While algorithms for identifying TM segments are available, modeling of the TM domains of α-helical MPs involves assembling the segments into a bundle. This requires the correct assignment of the buried and lipid-exposed faces of the TM domains.

Results: A recent increase in the number of crystal structures of α-helical MPs has enabled an analysis of the lipid-exposed surfaces and the interiors of such molecules on the basis of structure, rather than sequence alone. Together with a conservation criterion that is based on previous observations that conserved residues are mostly found in the interior of MPs, the bias of certain residue types to be preferably buried or exposed is proposed as a criterion for predicting the lipid-exposed and interior faces of TMs. Applications to known structures demonstrates 80% accuracy of this prediction algorithm.

Availability: The algorithm used for the predictions is implemented in the ProperTM Web server (http://icb.med.cornell.edu/services/propertm/start).
HMMGEP: clustering gene expression data using hidden Markov models
Authors: Ji Xinglai , Yuan Yuan , Li-Ling Jesse , Li Yanda , Sun Zhirong
Published: March 2004

Summary: The package HMMGEP performs cluster analysis on gene expression data using hidden Markov models.

Availability: HMMGEP, including the source code, documentation and sample data files, is available at http://www.bioinfo.tsinghua.edu.cn:8080/~rich/hmmgep_download/index.html.
Structural exon database, SEDB, mapping exon boundaries on multiple protein structures
Authors: Leslin Chesley M. , Abyzov Alex , Ilyin Valentin A.
Published: March 2004

Summary: Comparative analysis of exon/intron organization of genes and their resulting protein structures is important for understanding evolutionary relationships between species, rules of protein organization and protein functionality. We present Structural Exon Database (SEDB), with a Web interface, an application that allows users to retrieve the exon/intron organization of genes and map the location of the exon boundaries and the intron phase onto a multiple structural alignment. SEDB is linked with Friend, an integrated analytical multiple sequence/structure viewer, which allows simultaneous visualization of exon boundaries on structure and sequence alignments. With SEDB researchers can study the correlations of gene structure with the properties of the encoded three-dimensional protein structures across eukaryotic organisms.

Availability: SEDB is publicly available at http://glinka.bio.neu.edu/SEDB/SEDB.html

Supplementary information: On the SEDB Web site.
TOPALi: software for automatic identification of recombinant sequences within DNA multiple alignments
Authors: Milne Iain , Wright Frank , Rowe Glenn , Marshall David F. , Husmeier Dirk , McGuire Gràinne
Published: March 2004

Summary: TOPALi is a new Java graphical analysis application that allows the user to identify recombinant sequences within a DNA multiple alignment (either automatically or via manual investigation). TOPALi allows a choice of three statistical methods to predict the positions of breakpoints due to past recombination. The breakpoint predictions are then used to identify putative recombinant sequences and their relationships to other sequences. In addition to its sophisticated interface, TOPALi can import many sequence formats, estimate and display phylogenetic trees and allow interactive analysis and/or automatic HTML report generation.

Availability: TOPALi is freely available from http://www.bioss.ac.uk/software.html
FunMap: functional mapping of complex traits
Authors: Ma Chang-Xing , Wu Rongling , Casella George
Published: March 2004

Summary: FunMap is a Web-based user interface designed to map quantitative trait loci (QTL) affecting function-valued traits or infinite-dimensional traits in well-structured pedigrees or natural populations. User input includes three files: longitudinal trait data, marker genotypes and/or a linkage map. This software allows for a systematic genome-wide scan and significance test of QTL throughout the map. The dynamic change of QTL effects during the time course of growth is automatically drawn, from which specific biological hypotheses regarding the genetic control mechanisms of growth and development can be tested.

Availability:  http://web.biostat.ufl.edu/~cma/genetics/software.html
Second eigenvalue of the Laplacian matrix for predicting RNA conformational switch by mutation
Authors: Barash Danny
Published: March 2004

Motivation: Conformational switching in RNAs is thought to be of fundamental importance in several biological processes, including translational regulation, regulation of self-cleavage in viruses, protein biosynthesis and mRNA splicing. Current methods for detecting bi-stable RNAs that can lead to structural switching when triggered by an outside event rely on kinetics, energetics and properties of the combinatorial structure space of RNAs. Based on these properties, tools have been developed to predict whether a given sequence folds to a structure characterized by a bi-stable conformation, or to design multi-stable RNAs by an iterative algorithm. A useful addition is in developing a local procedure to prescribe, given an initial sequence, the least amount of mutations needed to drive the system into an optimal bi-stable conformation.

Results: We introduce a local procedure for predicting mutations, by generating and analyzing eigenvalue tables, that are capable of transforming the wild-type sequence into a bi-stable conformation. The method is independent of the folding algorithms but relies on their success. It can be used in conjunction with existing tools, as well as being incorporated into more general RNA prediction packages. We apply this procedure on three well-studied structures. First, the method is validated on the mutation leading to a conformational switch in the spliced leader RNA from Leptomonas collosoma, a mutation that has already been confirmed by an experiment. Second, the method is used to predict a mutation that can lead to a novel conformational switch in the P5abc subdomain of the group I intron ribozyme in Tetrahymena thermophila. Third, the method is applied on Hepatitis delta virus to predict mutations that transform the wild-type into a bi-stable conformation, a configuration assessed by calculating the free energies using folding prediction algorithms. The predictions in the final examples need to be verified experimentally, whereas the mutation predicted in the first example complies with the experiment. This supports the use of our proposed method on other known structures, as well as genetically engineered ones.

Availability: An eigenvalue application will be available in the near future attached to one of the existing tools.
Robust PCA and classification in biosciences
Authors: Hubert Mia , Engelen Sanne
Published: March 2004

Motivation: Principal components analysis (PCA) is a very popular dimension reduction technique that is widely used as a first step in the analysis of high-dimensional microarray data. However, the classical approach that is based on the mean and the sample covariance matrix of the data is very sensitive to outliers. Also, classification methods based on this covariance matrix do not give good results in the presence of outlying measurements.

Results: First, we propose a robust PCA (ROBPCA) method for high-dimensional data. It combines projection-pursuit ideas with robust estimation of low-dimensional data. We also propose a diagnostic plot to display and classify the outliers. This ROBPCA method is applied to several bio-chemical datasets. In one example, we also apply a robust discriminant method on the scores obtained with ROBPCA. We show that this combination of robust methods leads to better classifications than classical PCA and quadratic discriminant analysis.

Availability: All the programs are part of the Matlab Toolbox for Robust Calibration, available at http://www.wis.kuleuven.ac.be/stat/robust.html.
Visualization for genomics: the Microbial Genome Viewer
Authors: Kerkhoven Robert , van Enckevort Frank H. J. , Boekhorst Jos , Molenaar Douwe , Siezen Roland J.
Published: March 2004

Summary: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a MySQL database. The generated images are in scalable vector graphics (SVG) format, which is suitable for creating high-quality scalable images and dynamic Web representations. Gene-related data such as transcriptome and time-course microarray experiments can be superimposed on the maps for visual inspection.

Availability: The Microbial Genome Viewer 1.0 is freely available at http://www.cmbi.kun.nl/MGV
Improving false discovery rate estimation
Authors: Pounds Stan , Cheng Cheng
Published: March 2004

Motivation: Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of significant findings. However, such an interpretation of the q-value may be unwarranted considering that the q-value is based on an unstable estimator of the positive FDR (pFDR). Another method proposes estimating the FDR by modeling p-values as arising from a beta-uniform mixture (BUM) distribution. Unfortunately, the BUM approach is reliable only in settings where the assumed model accurately represents the actual distribution of p-values.

Methods: A method called the spacings LOESS histogram (SPLOSH) is proposed for estimating the conditional FDR (cFDR), the expected proportion of false positives conditioned on having k ‘significant’ findings. SPLOSH is designed to be more stable than the q-value and applicable in a wider variety of settings than BUM.

Results: In a simulation study and data analysis example, SPLOSH exhibits the desired characteristics relative to the q-value and BUM.

Availability: The Web site www.stjuderesearch.org/statistics/splosh.html has links to freely available S-plus code to implement the proposed procedure.
Research in progress: some preliminary and key insights into the information needs of the contemporary academic researcher. Part 1
Authors: Herman Eti
Published: March 2004

Reports the preliminary conclusions derived from the initial, pathfinder phase of a study devoted to a re‐assessment of the information needs of academic researchers. This exploration of researchers’ current information requirements and information seeking practices has been undertaken with a special emphasis on examining the validity of anything and everything we have customarily been holding true as to the information component of academic research work. The groundwork for the investigation has been laid down in a pilot project of seven in‐depth critical incident method based information needs interviews with faculty at the University of Haifa (Israel). The qualitative data thus obtained as to researchers’ information needs, how they go about meeting these needs, and the barriers they encounter in the process have been analysed within the comprehensive framework proposed for a systematic description of information needs. The ensuing evaluation considers 11 aspects of the present‐day academic researcher’s information needs: subject, function, nature, intellectual level, viewpoint, quantity, quality/authority, date/currency, speed of delivery, place of publication/origin, and processing/packaging.
Adrift in the mainstream: Challenges facing the UK vegetarian movement
Authors: Smart Andrew
Published: March 2004

Assesses how the mainstream availability and acceptability of vegetarian food has impacted on the organised vegetarian movement in the UK. Presents data collected during an ethnographic case study to show the dilemmas facing the leading UK vegetarian organisation during the mid‐1990s. In order to understand these dilemmas distinguishes between vegetarian food and the ideology of vegetarianism, using existing evidence about variability in diets, motives and organisational politics. When reflecting on the implications of the case study suggests that mainstream acceptance is a double‐edged sword that facilitates the adoption of the diet but threatens the moral foundations of the ideology.
Segmenting the convenience and health trends in the British food market
Authors: Shiu Eric C.C. , Dawson John A. , Marshall David W.
Published: March 2004

Convenience and health trends are arguably the two most prevailing consumption trends in the British food market, with single‐adult households as keener followers than many other household types. Two portfolios of food products have been developed as proxies of the twin trends respectively, and the Poisson regression technique is employed to segment these two trend markets. Results confirm some previously held views, challenge others, and make some serendipity that has not been found in previous studies. Marketers are informed of greater accessibility in the health trend market vis‐à‐vis the convenience trend market for segmentation purpose, and are advised to treat the two trend markets as non‐overlapping. A number of future research directions, including a multivariate measure of the aspiration intensity of the two food trends and a measure of the twin trends for a wider range of typical products within the consumer market, are suggested.
Internationalisation strategies of food‐testing firms in the changing Nordic market
Authors: Orava Markus , Wiklund Patricia
Published: March 2004

The growing interest in food safety has led to food‐testing services becoming an issue of increasing importance. The demand for outsourced food‐testing services is growing. One of the results of these developments has been the internationalisation of such firms. This paper analyses the internationalisation of food‐testing services in the light of developments in the Nordic food‐testing market. The focus is on the external elements. These include development of the market to allow food‐testing firms to overcome problems and exploit opportunities arising from the fundamental changes in the nature of the market. The adopted internationalisation strategies of the Nordic food‐testing companies are studied. The key driver for internationalisation of firms is growth. Successful firms also need to maintain high levels of quality, speed of delivery, and competitive pricing.
Mikron extends modularization
Authors: Bloss Richard
Published: March 2004

Modularization continues to evolve in the automated assembly system business. Mikron Technology Group, a Swiss headquartered system developer, has extended modularization beyond structure construction, workstation modules to modularization of the controls for flexibility in design, development as well as operation.
Building a mini‐assembly system from a technology construction kit
Authors: Gaugel Tobias , Bengel Matthias , Malthan Dirk
Published: March 2004

As part of this paper, extracts will be presented from the results of the joint project “MiniProd”, which is carried out by the Fraunhofer IPA together with industrial partners and sponsored by the BMBF (Federal Ministry for Education and Research/02PD2370). The aim of the research project is to develop a marketable, miniaturized highly‐flexible micro‐assembly system capable of reproducing the correct size proportions between a product and its production environment and also able to intelligently integrate processes which had earlier run separately.
Force‐guided robot in automated assembly of mobile phone: overcoming component misalignment
Authors: Suh Chin Kong , Maran Ratnam Mani , Mandava Rajeswari
Published: March 2004

This paper describes the development of a force‐guided robot that uses the information of contact force to overcome component misalignment in the automated assembly of a mobile phone. Several possibilities of misalignment in the assembly of the back chassis and front housing of the mobile phone are studied. An assembly approach using force‐guided motion is implemented to perform the assembly task. The assembly operation was carried out in the presence of translational and rotational misalignment of the mating components. Experimental results show that the proposed assembly approach successfully performs the assembly task.
Gender and instructional outcomes
Authors: Ochieng Walumbwa Fred , Wu Cindy , Ojode Lucy A.
Published: March 2004

This article examines how perceived instructor leadership style mediates the students' gender‐instruction effectiveness relationship. We administered the multifactor leadership questionnaire to a convenient sample of 360 undergraduate and graduate students drawn from a mid‐west research university (USA) over two consecutive semesters. Partial mediation was indicated as students' gender discriminated perception of certain instructor leadership styles that were positively associated with instructional outcomes. However, gender itself did not discriminate instructional outcomes. Further our results showed that both female and male students converged on unfavorable assessment of instructors who exhibit passive management‐by‐exception. These instructors were perceived as ineffective, unable to draw extra effort, and unsatisfactory. Overall, the results indicated a favorable assessment of active management‐by‐exemption, contingent reward, and transformational leadership behaviors by both genders. This research therefore indicates the importance of these three leadership skills for instruction and learning effectiveness.
Team feedback based on dialogue
Authors: Jabri Muayyad
Published: March 2004

Recent work in change management has emphasized the role of feedback in creating a readiness for, and contributing to acceptance of, the need for change. This article illustrates the development and application of an intervention protocol where differences in perceptual location among team members of an R&D team were used as a springboard for inducing them to talk more openly about their differences and to help them see how change could be constructed through dialogue as a medium. To the extent that team members were willing to create shared meaning, rather than gaining agreement on one meaning, they were more able to learn from each other and to “criss‐cross” their views with each other, thus enhancing their understanding of the sorts of issues that are impeding their ability to perform.
Strategic marketing planning: a twenty‐first century perspective
Authors: Keegan Warren J.
Published: March 2004

Looks back at the Viewpoint from the first issue of International Marketing Review in order to reflect on how things have changed in the intervening 21 year period. The author then explains that he sees a continuation of the driving and restraining forces that have shaped global markets for the past half century. If the terrorist and other threats to world peace are contained or resolved, the final critical driver for further globalization is management vision.