BiNoM: a Cytoscape plugin for manipulating and analyzing biological networks

BiNoM (Biological Network Manager) is a new bioinformatics software that significantly facilitates the usage and the analysis of biological networks in standard systems biology formats (SBML, SBGN, BioPAX). BiNoM implements a full-featured BioPAX editor and a method of 'interfaces' for accessing BioPAX content. BiNoM is able to work with huge BioPAX files such as whole pathway databases. In addition, BiNoM allows the analysis of networks created with CellDesigner software and their conversion into BioPAX format. BiNoM comes as a library and as a Cytoscape plugin which adds a rich set of operations to Cytoscape such as path and cycle analysis, clustering sub-networks, decomposition of network into modules, clipboard operations and others. AVAILABILITY: Last version of BiNoM distributed under the LGPL licence together with documentation, source code and API are available at http://bioinfo.curie.fr/projects/binom     

Representations of molecular pathways: an evaluation of SBML, PSI MI and BioPAX

MOTIVATION: Analysis and simulation of pathway data is of high importance in bioinformatics. Standards for representation of information about pathways are necessary for integration and analysis of data from various sources. Recently, a number of representation formats for pathway data, SBML, PSI MI and BioPAX, have been proposed. RESULTS: In this paper we compare these formats and evaluate them with respect to their underlying models, information content and possibilities for easy creation of tools. The evaluation shows that the main structure of the formats is similar. However, SBML is tuned towards simulation models of molecular pathways while PSI MI is more suitable for representing details about particular interactions and experiments. BioPAX is the most general and expressive of the formats. These differences are apparent in allowed information and the structure for representation of interactions. We discuss the impact of these differences both with respect to information content in existing databases and computational properties for import and analysis of data.     

BioPP: a tool for web-publication of biological networks

Background  

Cellular processes depend on the function of intracellular molecular networks. The curation of the literature relevant to specific biological pathways is important for many theoretical and experimental research teams and communities. No current tool supports web publication or hosting of user-developed large scale annotated pathway diagrams. Sharing via web publication is needed to allow real-time access to the current literature pathway knowledgebase, both privately within a research team or publicly among the outside research community. Web publication also facilitates team and/or community input into the curation process while allowing centralized control of the curation and validation process. We have developed new tool to address these needs. Biological Pathway Publisher (BioPP) is a software suite for converting CellDesigner Systems Biology Markup Language (CD-SBML) formatted pathways into a web viewable format. The BioPP suite is available for private use and for depositing knowledgebases into a newly created public repository.     

Integrating biological pathways and genomic profiles with ChiBE 2

Background

Dynamic visual exploration of detailed pathway information can help researchers digest and interpret complex mechanisms and genomic datasets.

Results

ChiBE is a free, open-source software tool for visualizing, querying, and analyzing human biological pathways in BioPAX format. The recently released version 2 can search for neighborhoods, paths between molecules, and common regulators/targets of molecules, on large integrated cellular networks in the Pathway Commons database as well as in local BioPAX models. Resulting networks can be automatically laid out for visualization using a graphically rich, process-centric notation. Profiling data from the cBioPortal for Cancer Genomics and expression data from the Gene Expression Omnibus can be overlaid on these networks.

Conclusions

ChiBE’s new capabilities are organized around a genomics-oriented workflow and offer a unique comprehensive pathway analysis solution for genomics researchers. The software is freely available at http://code.google.com/p/chibe.     

mmsearch: a motif arrangement language and search program.

This paper presents a language for describing arrangements of motifs in biological sequences, and a program that uses the language to find the arrangements in motif match databases. The program does not by itself search for the constituent motifs, and is thus independent of how they are detected, which allows it to use motif match data of various origins. AVAILABILITY: The program can be tested online at http://hits.isb-sib.ch and the distribution is available from ftp://ftp.isrec.isb-sib.ch/pub/software/unix/mmsearch-1.0.tar.gz CONTACT: Thomas.Junier@isrec.unil.ch SUPPLEMENTARY INFORMATION: The full documentation about mmsearchis available from http://hits.isb-sib.ch/~tjunier/mmsearch/doc.     

VARSPLIC: alternatively-spliced protein sequences derived from SWISS-PROT and TrEMBL

SUMMARY: The program varsplic.pl uses information present in the SWISS-PROT and TrEMBL databases to create new records for alternatively spliced isoforms. These new records can be used in similarity searches. AVAILABILITY: The program is available at ftp://ftp.ebi.ac.uk/pub/software/swissprot/, together with regularly updated output files. CONTACT: pkersey@ebi.ac.uk     

Databases and software for the analysis of mutations in the human p53 gene, the human hprt gene and the lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations in the human p53 gene, the human hprt gene and the rodent transgenic lacZ locus. The databases themselves are stand-alone dBase files and the software for analysis of the databases runs on IBM- compatible computers. The software created for these databases permits filtering, ordering, report generation and display of information in the database. In addition, a significant number of routines have been developed for the analysis of single base substitutions. One method of obtaining the databases and software is via the World Wide Web (WWW). Open home page http://sunsite.unc.edu/dnam/mainpage.ht ml with a WWW browser. Alternatively, the databases and programs are available via public ftp from anonymous@sunsite.unc.edu. There is no password required to enter the system. The databases and software are found in subdirectory pub/academic/biology/dna-mutations. Two other programs are available at the WWW site, a program for comparison of mutational spectra and a program for entry of mutational data into a relational database.     

Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis

SUMMARY: The purpose of this work is to provide the modern molecular geneticist with tools to perform more efficient and more accurate analysis of the genotype data they produce. By using Microsoft Excel macros written in Visual Basic, we can translate genotype data into a form readable by the versatile software 'Arlequin', read the Arlequin output, calculate statistics of linkage disequilibrium, and put the results in a format for viewing with the software 'GOLD'. AVAILABILITY: The software is available by FTP at: ftp://xcsg.iarc.fr/cox/Genotype_Transposer/. SUPPLEMENTARY INFORMATION: Detailed instruction and examples are available at: ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at: http://lgb.unige.ch/arlequin/. GOLD is available at: http://www.well.ox.ac.uk/asthma/GOLD/.     

EC_oligos: automated and whole-genome primer design for exons within one or between two genomes

SUMMARY: EC_oligos designs oligonucleotides (oligos) from exons of annotated genomic sequence information. It can automatically and rapidly select oligos that are conserved between two sets of sequence data, and can pair up oligos for use as PCR primers. It can do this on a whole-genome scale and according to user-defined criteria. AVAILABILITY: The source code, executable program and user manual are available at ftp://ftp.ebi.ac.uk/pub/software/dos/EC_oligos/.     

InterProScan--an integration platform for the signature-recognition methods in InterPro

InterProScan is a tool that scans given protein sequences against the protein signatures of the InterPro member databases, currently--PROSITE, PRINTS, Pfam, ProDom and SMART. The number of signature databases and their associated scanning tools as well as the further refinement procedures make the problem complex. InterProScan is designed to be a scalable and extensible system with a robust internal architecture. AVAILABILITY: The Perl-based InterProScan implementation is available from the EBI ftp server (ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/) and the SRS-basedInterProScan is available upon request. We provide the public web interface (http://www.ebi.ac.uk/interpro/scan.html) as well as email submission server (interproscan@ebi.ac.uk).     

An automated comparative analysis of 17 complete microbial genomes

MOTIVATION: As sequenced genomes become larger and sequencing becomes faster, there is a need to develop accurate automated genome comparison techniques and databases to facilitate derivation of genome functionality; identification of enzymes, putative operons and metabolic pathways; and to derive phylogenetic classification of microbes. RESULTS: This paper extends an automated pair-wise genome comparison technique (Bansal et al., Math. Model. Sci. Comput., 9, 1-23, 1998, Bansal and Bork, in First International Workshop of Declarative Languages, Springer, pp. 275-289, 1999) used to identify orthologs and gene groups to derive orthologous genes in a group of genomes and to identify genes with conserved functionality. Seventeen microbial genomes archived at ftp://ncbi.nlm.nih.gov/genbank/genomes have been compared using the automated technique. Data related to orthologs, gene groups, gene duplication, gene fusion, orthologs with conserved functionality, and genes specifically orthologous to Escherichia coli and pathogens has been presented and analyzed. AVAILABILITY: A prototype database is available at ftp://www.mcs.kent.edu/arvind/intellibio / orthos.html. The software is free for academic research under an academic license. The detailed database for every microbial genome in NCBI is commercially available through intellibio software and consultancy corporation (Web site: http://www.mcs.kent.edu/?rvind/intellibio . html). CONTACT: arvind@mcs.kent.edu.     

BioDownloader: bioinformatics downloads and updates in a few clicks

There are many ftp or http servers storing data required for biological research. While some download applications are available, there is no user-friendly download application with a graphical interface specifically designed and adapted to meet the requirements of bioinformatics. BioDownloader is a program for downloading and updating files from ftp and http servers. It is optimized to work robustly with large numbers of files. It allows the selective retrieval of only the required files (batch downloads, multiple file masks, ls-lR file parsing, recursive search, recent updates, etc.). BioDownloader has a built-in repository containing the settings for common bioinformatics file-synchronization needs, including the Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) databases. It can post-process downloaded files, including archive extraction and file conversions. AVAILABILITY: The program can be installed from http://dunbrack.fccc.edu/BioDownloader. The software is freely available for both non-commercial and commercial users under the BSD license.     

cPath: open source software for collecting, storing, and querying biological pathways

Background  

Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required.     

The role of bioinformatics in pathway curation

Diagrams and models of biological pathways are useful tools in biology. Pathway diagrams are mainly used for illustrative purposes for instance in textbooks and in presentations. Pathway models are used in the analysis of genomic data. Bridging the gap between diagrams and models allows not only the analysis of genomics data and interactions but also the visualisation of the results in a variety of different ways. The knowledge needed for pathway creation and curation is available from three distinct sources: databases, literature and experts. We describe the role of bioinformatics in facilitating the creation and curation of pathway.     

MedicCyc: a biochemical pathway database for Medicago truncatula

MOTIVATION: There is an imperative need to integrate functional genomics data to obtain a more comprehensive systems-biology view of the results. We believe that this is best achieved through the visualization of data within the biological context of metabolic pathways. Accordingly, metabolic pathway reconstruction was used to predict the metabolic composition for Medicago truncatula and these pathways were engineered to enable the correlated visualization of integrated functional genomics data. Results: Metabolic pathway reconstruction was used to generate a pathway database for M. truncatula (MedicCyc), which currently features more than 250 pathways with related genes, enzymes and metabolites. MedicCyc was assembled from more than 225,000 M. truncatula ESTs (MtGI Release 8.0) and available genomic sequences using the Pathway Tools software and the MetaCyc database. The predicted pathways in MedicCyc were verified through comparison with other plant databases such as AraCyc and RiceCyc. The comparison with other plant databases provided crucial information concerning enzymes still missing from the ongoing, but currently incomplete M. truncatula genome sequencing project. MedicCyc was further manually curated to remove non-plant pathways, and Medicago-specific pathways including isoflavonoid, lignin and triterpene saponin biosynthesis were modified or added based upon available literature and in-house expertise. Additional metabolites identified in metabolic profiling experiments were also used for pathway predictions. Once the metabolic reconstruction was completed, MedicCyc was engineered to visualize M. truncatula functional genomics datasets within the biological context of metabolic pathways. Availability: freely accessible at http://www.noble.org/MedicCyc/     

iPfam: visualization of protein-protein interactions in PDB at domain and amino acid resolutions

SUMMARY: There are many resources that contain information about binary interactions between proteins. However, protein interactions are defined by only a subset of residues in any protein. We have implemented a web resource that allows the investigation of protein interactions in the Protein Data Bank structures at the level of Pfam domains and amino acid residues. This detailed knowledge relies on the fact that there are a large number of multidomain proteins and protein complexes being deposited in the structure databases. The resource called iPfam is hosted within the Pfam UK website. Most resources focus on the interactions between proteins; iPfam includes these as well as interactions between domains in a single protein. AVAILABILITY: iPfam is available on the Web for browsing at http://www.sanger.ac.uk/Software/Pfam/iPfam/; the source-data for iPfam is freely available in relational tables via the ftp site ftp://ftp.sanger.ac.uk/pub/databases/Pfam/database_files/.