Binary state pattern clustering: a digital paradigm for class and biomarker discovery in gene microarray studies of cancer.

Class and biomarker discovery continue to be among the preeminent goals in gene microarray studies of cancer. We have developed a new data mining technique, which we call Binary State Pattern Clustering (BSPC) that is specifically adapted for these purposes, with cancer and other categorical datasets. BSPC is capable of uncovering statistically significant sample subclasses and associated marker genes in a completely unsupervised manner. This is accomplished through the application of a digital paradigm, where the expression level of each potential marker gene is treated as being representative of its discrete functional state. Multiple genes that divide samples into states along the same boundaries form a kind of gene-cluster that has an associated sample-cluster. BSPC is an extremely fast deterministic algorithm that scales well to large datasets. Here we describe results of its application to three publicly available oligonucleotide microarray datasets. Using an alpha-level of 0.05, clusters reproducing many of the known sample classifications were identified along with associated biomarkers. In addition, a number of simulations were conducted using shuffled versions of each of the original datasets, noise-added datasets, as well as completely artificial datasets. The robustness of BSPC was compared to that of three other publicly available clustering methods: ISIS, CTWC and SAMBA. The simulations demonstrate BSPC's substantially greater noise tolerance and confirm the accuracy of our calculations of statistical significance.     

Combo: a whole genome comparative browser

SUMMARY: Combo is a comparative genome browser that provides a dynamic view of whole genome alignments along with their associated annotations. Combo provides two different visualization perspectives. The perpendicular (dot plot) view provides a dot plot of genome alignments synchronized with a display of genome annotations along each axis. The parallel view displays two genome annotations horizontally, synchronized through a panel displaying local alignments as trapezoids. Users can zoom to any resolution, from whole chromosomes to individual bases. They can select, highlight and view detailed information from specific alignments and annotations. Combo is an organism agnostic and can import data from a variety of file formats. AVAILABILITY: Combo is integrated as part of the Argo Genome Browser which also provides single-genome browsing and editing capabilities. Argo is written in Java, runs on multiple platforms and is freely available for download at http://www.broad.mit.edu/annotation/argo/.     

An integrated database for the enhanced identification of silkworm gene resources

The National Academy of Agricultural Science (NAAS) has developed a web-based database to provide characterization information in silkworm. The silkworm database has four major function menus: variety searching, characterization viewing, general information and photo gallery. It provides 321 silkworm varieties characterization information for six different regions namely, Korean, Japanese, Chinese, European, Tropical and non-classified group. Additionally, the database provides 1,132 photo images regarding life cycle of various silkworm varieties. A specific characterization information table provides accession number, variety, strain and larval marking, blood color, cocoon color, cocoon shape, egg colors, remarks and image table provides photos which consist of shape and color in the different stages of larval, egg and cocoon stages. AVAILABILITY: The database is available for free at http://www.naas.go.kr/silkworm/english/     

WebVar: A resource for the rapid estimation of relative site variability from multiple sequence alignments

WebVar is an online resource that provides estimates of relative site variability from multiple alignments of homologous protein or nucleic acid sequences. WebVar provides a variety of graphic and textual representations of estimates, designed to assist in phylogenetic analysis. AVAILABILITY: The WebVar server is located at http://www.pesolelab.it/Tools/WebVar.html     

Applications of Tree-Maps to hierarchical biological data

SUMMARY: A brief overview of Tree-Maps provides the basis for understanding two new implementations of Tree-Map methods. TreeMapClusterView provides a new way to view microarray gene expression data, and GenePlacer provides a view of gene ontology annotation data. We also discuss the benefits of Tree-Maps to visualize complex hierarchies in functional genomics. AVAILABILITY: Java class files are freely available at http://mendel.mc.duke.edu/bioinformatics/ CONTACT: mccon012@mc.duke.edu SUPPLEMENTARY INFORMATION: For more information on TreeMapClusterView (see http://mendel.mc.duke.edu/bioinformatics/software/boxclusterview/), and http://mendel.mc.duke.edu/bioinformatics/software/geneplacer/).     

PathAligner

MOTIVATION: Analysis of metabolic pathways is a central topic in understanding the relationship between genotype and phenotype. The rapid accumulation of biological data provides the possibility of studying metabolic pathways at both the genomic and the metabolic levels. Retrieving metabolic pathways from current biological data sources, reconstructing metabolic pathways from rudimentary pathway components, and aligning metabolic pathways with each other are major tasks. Our motivation was to develop a conceptual framework and computational system that allows the retrieval of metabolic pathway information and the processing of alignments to reveal the similarities between metabolic pathways. RESULTS: PathAligner extracts metabolic information from biological databases via the Internet and builds metabolic pathways with data sources of genes, sequences, enzymes, metabolites etc. It provides an easy-to-use interface to retrieve, display and manipulate metabolic information. PathAligner also provides an alignment method to compare the similarity between metabolic pathways. AVAILABILITY: PathAligner is available at http://bibiserv.techfak.uni-bielefeld.de/pathaligner.     

Rainbow: a toolbox for phylogenetic supertree construction and analysis

Rainbow is a program that provides a graphic user interface to construct supertrees using different methods. It also provides tools to analyze the quality of the supertrees produced. Rainbow is available for Mac OS X, Windows and Linux. AVAILABILITY: Rainbow is a free open-source software. Its binary files, source code, and manual can be downloaded from the Rainbow web page: http://genome.cs.iastate.edu/Rainbow/     

APOPTO-CELL--a simulation tool and interactive database for analyzing cellular susceptibility to apoptosis

We have developed a web service that provides a comprehensive analysis of the susceptibility of cells to undergo apoptosis in response to an activation of the mitochondrial apoptotic pathway. Based on ordinary differential equations, (pre-determined) protein concentrations and release kinetics of mitochondrial pro-apoptotic factors, a network of 52 reactions and 19 reaction partners can be employed as a tool to display temporal protein profiles, to identify key regulatory proteins and to determine critical threshold concentrations required for the execution of apoptosis in HeLa cancer cells or other cell types. The web service also provides an interactive database function for the deposition of cell-type-specific quantitative data. In addition, the web service provides an output that can be compared directly to experimental results obtained from real-time single-cell experiments, making this a widely applicable systems biology tool for apoptosis and cancer researchers. AVAILABILITY: http://systemsbiology.rcsi.ie/apopto-cell.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

The Los Alamos hepatitis C sequence database

MOTIVATION: The hepatitis C virus (HCV) is a significant threat to public health worldwide. The virus is highly variable and evolves rapidly, making it an elusive target for the immune system and for vaccine and drug design. At present, some 30 000 HCV sequences have been published. A central website that provides annotated sequences and analysis tools will be helpful to HCV scientists worldwide. RESULTS: The HCV sequence database collects and annotates sequence data and provides them to the public via a website that contains a user-friendly search interface and a large number of sequence analysis tools, based on the model of the highly regarded Los Alamos HIV database. The HCV sequence database was officially launched in September 2003. Since then, its usage has steadily increased and is now at an average of approximately 280 visits per day from distinct IP addresses. AVAILABILITY: The HCV website can be accessed via http://hcv.lanl.gov and http://hcv-db.org.     

An integrated database to enhance the identification of SNP markers for rice

The National Academy of Agricultural Science (NAAS) has developed a web-based marker database to provide information about SNP markers in rice. The database consists of three major functional categories: map viewing, marker searching and gene annotation. It provides 12,829 SNP markers information including gene location information on 12 chromosomes in rice. The annotation of SNP marker provides information such as marker name, EST number, gene definition and general marker information. Users are assisted in tracing any new structures of the chromosomes and gene positional functions using specific SNP markers. AVAILABILITY: The database is available for free at http://nabic.niab.go.kr/SNP/     

BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing

SUMMARY: Manual processing of DNA methylation data from bisulfite sequencing is a tedious and error-prone task. Here we present an interactive software tool that provides start-to-end support for this process. In an easy-to-use manner, the tool helps the user to import the sequence files from the sequencer, to align them, to exclude or correct critical sequences, to document the experiment, to perform basic statistics and to produce publication-quality diagrams.Emphasis is put on quality control: The program automatically assesses data quality and provides warnings and suggestions for dealing with critical sequences. The BiQ Analyzer program is implemented in the Java programming language and runs on any platform for which a recent Java virtual machine is available. AVAILABILITY: The program is available without charge for non-commercial users and can be downloaded from http://biq-analyzer.bioinf.mpi-inf.mpg.de/     

The Influence of Facial Characteristics on the Relation between Male 2D:4D and Dominance

Although relations between 2D:4D and dominance rank in both baboons and rhesus macaques have been observed, evidence in humans is mixed. Whereas behavioral patterns in humans have been discovered that are consistent with these animal findings, the evidence for a relation between dominance and 2D:4D is weak or inconsistent. The present study provides experimental evidence that male 2D:4D is related to dominance after (fictitious) male-male interaction when the other man has a dominant, but not a submissive or neutral face. This finding provides evidence that the relationship between 2D:4D and dominance emerges in particular, predictable situations and that merely dominant facial characteristics of another person are enough to activate supposed relationships between 2D:4D and dominance.     

Interactive gene-order comparison for multiple small genomes

SUMMARY: The Genome Organization Analysis Tool (GOAT) is a program that performs comparative sequence analysis on ordered gene lists from annotated genomes, provides visual and tabular output, and provides means of accessing and analyzing related gene sequence data, for the purpose of comparing genome organization at the gene-order level. GOAT can be used to compare any two or more genomes or chromosomes on demand, or configured to provide access to precomputed comparisons of a specific group of genome sequences. AVAILABILITY: Demonstration web server and software download, subject to the Virginia Tech Noncommercial License are available at http://gaia.biotech.vt.edu/goat/. SUPPLEMENTARY INFORMATION: Updates, installation and configuration information are available at http://gaia.biotech.vt.edu/goat.     

The ModFOLD server for the quality assessment of protein structural models

The reliable assessment of the quality of protein structural models is fundamental to the progress of structural bioinformatics. The ModFOLD server provides access to two accurate techniques for the global and local prediction of the quality of 3D models of proteins. Firstly ModFOLD, which is a fast Model Quality Assessment Program (MQAP) used for the global assessment of either single or multiple models. Secondly ModFOLDclust, which is a more intensive method that carries out clustering of multiple models and provides per-residue local quality assessment. AVAILABILITY: http://www.biocentre.rdg.ac.uk/bioinformatics/ModFOLD/.     

Swissknife - 'lazy parsing' of SWISS-PROT entries.

SUMMARY: We present Swissknife, a set of Perl modules which provides a fast and reliable object-oriented interface to parsing and modifying files in SWISS-PROT format. AVAILABILITY: The Swissknife modules are available at ftp://ftp.ebi.ac. uk/pub/software/swissprot/. CONTACT: hhe@ebi.ac.uk     

Measuring Corporate Environmental Performance: The ICI Environmental Burden System

The Imperial Chemical Industries (ICI) group has developed a method, called the “environmental burden system” to rank the potential environmental impacts of its emissions and wastes. The method uses potency factors to characterize the potential environmental impacts of wastes and emissions in ten major impact categories. When compared to the more traditional approach of reporting the total mass of emissions and wastes, the environmental burden approach provides a more meaningful picture of the potential impact of emissions: it helps identi?. the most harmful wastes and emissions; it provides the public with a better understanding ofthe potential impact of company operations: and it helps communicate the effectiveness of waste and emission reduction programs     

A weight of evidence approach for selecting exposure biomarkers for biomonitoring

Context: It is known that there are usually several biomarkers and/or medium combinations that can be applied to answer a specific exposure question. To help determine an appropriate combination for the specific question, we have developed a weight-of-evidence Framework that provides a relative appropriateness score for competing combinations.

Methods: The Framework is based on an expert assessor’s evaluation of the relevance and suitability of the biomarker and medium for the question based on a set of criteria. We provide a computer based modeling tool to guide the researcher through the process.

Results: We present an example with six biomarkers of benzene exposure in one matrix; the six are either the most commonly used biomarkers and/or have recent widespread usage. The example clearly demonstrates the usefulness of the Framework for scoring the choices, as well as the transparency of the method that provides the basis for discussion.

Conclusions: The Framework provides for the first time a method to transparently document the rationale behind selecting, from among a set of alternatives, the most scientifically supportable exposure biomarker to address a specific biomonitoring question, thus providing a reproducible account of expert opinions on the suitability of a biomarker.     

Predicting class II MHC/peptide multi-level binding with an iterative stepwise discriminant analysis meta-algorithm.

MOTIVATION: Predicting peptides that bind to both Major Histocompatibility Complex (MHC) molecules and T cell receptors provides crucial information for vaccine development. An agretope is that portion of a peptide that interacts with an MHC molecule. The identification and prediction of agretopes is the first step towards vaccine design. RESULTS: An iterative stepwise discriminant analysis meta-algorithm is utilized to derive a quantitative motif for classifying potential agretopes as high-, moderate- or non-binders for HLA-DR1, a class II MHC molecule. A large molecular online database provides the input for this data-driven algorithm. The model correctly classifies over 85% of the peptides in the database. AVAILABILITY: Stepwise discriminant analysis software is available commercially in SPSS and BMDP statistical software packages. Peptides known to bind MHC molecules can be downloaded from http://wehih.wehi.edu.au/mhcpep/. Peptides known not to bind HLA-DR1 are available from the author upon request. CONTACT: ronna@ucsfresno.edu.     

An extensible application for assembling annotation for genomic data

SUMMARY: AnnBuilder is an R package for assembling genomic annotation data. The system currently provides parsers to process annotation data from LocusLink, Gene Ontology Consortium, and Human Gene Project and can be extended to new data sources via user defined parsers. AnnBuilder differs from other existing systems in that it provides users with unlimited ability to assemble data from user selected sources. The products of AnnBuilder are files in XML format that can be easily used by different systems. AVAILABILITY: (http://www.bioconductor.org). Open source.