Briefings in Bioinformatics

Bioinformatics, multiscale modeling and the IUPS Physiome Project.

Publication Date: 2008 May 13 PMID: 18477639
Authors: Hunter, P. J. - Crampin, E. J. - Nielsen, P. M.
Journal: Brief Bioinform

Multiscale modeling is required for linking physiological processes operating at the organ and tissue levels to signal transduction networks and other subcellular processes. Several XML markup languages, including CellML, have been developed to encode models and to facilitate the building of model repositories and general purpose software tools. Progress in this area is described and illustrated with reference to the heart Physiome Project which aims to understand cardiac arrhythmias in terms of structure-function relations from proteins up to cells, tissues and organs.

post to: CiteULike

VisANT: an integrative framework for networks in systems biology.

Publication Date: 2008 May 7 PMID: 18463131
Authors: Hu, Z. - Snitkin, E. S. - Delisi, C.
Journal: Brief Bioinform

The essence of a living cell is adaptation to a changing environment, and a central goal of modern cell biology is to understand adaptive change under normal and pathological conditions. Because the number of components is large, and processes and conditions are many, visual tools are useful in providing an overview of relations that would otherwise be far more difficult to assimilate. Historically, representations were static pictures, with genes and proteins represented as nodes, and known or inferred correlations between them (links) represented by various kinds of lines. The modern challenge is to capture functional hierarchies and adaptation to environmental change, and to discover pathways and processes embedded in known data, but not currently recognizable. Among the tools being developed to meet this challenge is VisANT (freely available at http://visant.bu.edu) which integrates, mines and displays hierarchical information. Challenges to integrating modeling (discrete or continuous) and simulation capabilities into such visual mining software are briefly discussed.

post to: CiteULike

The Beta Workbench: a computational tool to study the dynamics of biological systems.

Publication Date: 2008 May 7 PMID: 18463130
Authors: Dematte, L. - Priami, C. - Romanel, A.
Journal: Brief Bioinform

We introduce the Beta Workbench (BWB), a scalable tool built on top of the newly defined BlenX language to model, simulate and analyse biological systems. We show the features and the incremental modelling process supported by the BWB on a running example based on the mitogen-activated kinase pathway. Finally, we provide a comparison with related approaches and some hints for future extensions.

post to: CiteULike

Computational intelligence approaches for pattern discovery in biological systems.

Publication Date: 2008 May 5 PMID: 18460474
Authors: Fogel, G. B.
Journal: Brief Bioinform

Biology, chemistry and medicine are faced by tremendous challenges caused by an overwhelming amount of data and the need for rapid interpretation. Computational intelligence (CI) approaches such as artificial neural networks, fuzzy systems and evolutionary computation are being used with increasing frequency to contend with this problem, in light of noise, non-linearity and temporal dynamics in the data. Such methods can be used to develop robust models of processes either on their own or in combination with standard statistical approaches. This is especially true for database mining, where modeling is a key component of scientific understanding. This review provides an introduction to current CI methods, their application to biological problems, and concludes with a commentary about the anticipated impact of these approaches in bioinformatics.

post to: CiteULike

Biodiversity informatics: the challenge of linking data and the role of shared identifiers.

Publication Date: 2008 Apr 29 PMID: 18445641
Authors: Page, R. D.
Journal: Brief Bioinform

A major challenge facing biodiversity informatics is integrating data stored in widely distributed databases. Initial efforts have relied on taxonomic names as the shared identifier linking records in different databases. However, taxonomic names have limitations as identifiers, being neither stable nor globally unique, and the pace of molecular taxonomic and phylogenetic research means that a lot of information in public sequence databases is not linked to formal taxonomic names. This review explores the use of other identifiers, such as specimen codes and GenBank accession numbers, to link otherwise disconnected facts in different databases. The structure of these links can also be exploited using the PageRank algorithm to rank the results of searches on biodiversity databases. The key to rich integration is a commitment to deploy and reuse globally unique, shared identifiers [such as Digital Object Identifiers (DOIs) and Life Science Identifiers (LSIDs)], and the implementation of services that link those identifiers.

post to: CiteULike

The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation.

Publication Date: 2008 Apr 24 PMID: 18436575
Authors: Wingender, E.
Journal: Brief Bioinform

Since its beginning as a data collection more than 20 years ago, the TRANSFAC project underwent an evolution to become the basis for a complex platform for the description and analysis of gene regulatory events and networks. In the following, I describe what the original concepts were, what their present status is and how they may be expected to contribute to future system biology approaches.

post to: CiteULike

A critical examination of stoichiometric and path-finding approaches to metabolic pathways.

Publication Date: 2008 Apr 24 PMID: 18436574
Authors: Planes, F. J. - Beasley, J. E.
Journal: Brief Bioinform

Advances in the field of genomics have enabled computational analysis of metabolic pathways at the genome scale. Singular attention has been devoted in the literature to stoichiometric approaches, and path-finding approaches, to metabolic pathways. Stoichiometric approaches make use of reaction stoichiometry when trying to determine metabolic pathways. Stoichiometric approaches involve elementary flux modes and extreme pathways. In contrast, path-finding approaches propose an alternative view based on graph theory in which reaction stoichiometry is not considered. Path-finding approaches use shortest path and k-shortest path concepts. In this article we give a critical overview of the theory, applications and key research challenges of stoichiometric and path-finding approaches to metabolic pathways.

post to: CiteULike

Protein structure databases with new web services for structural biology and biomedical research.

Publication Date: 2008 Apr 22 PMID: 18430752
Authors: Standley, D. M. - Kinjo, A. R. - Kinoshita, K. - Nakamura, H.
Journal: Brief Bioinform

The Protein Data Bank Japan (PDBj) curates, edits and distributes protein structural data as a member of the worldwide Protein Data Bank (wwPDB) and currently processes approximately 25-30% of all deposited data in the world. Structural information is enhanced by the addition of biological and biochemical functional data as well as experimental details extracted from the literature and other databases. Several applications have been developed at PDBj for structural biology and biomedical studies: (i) a Java-based molecular graphics viewer, jV; (ii) display of electron density maps for the evaluation of structure quality; (iii) an extensive database of molecular surfaces for functional sites, eF-site, as well as a search service for similar molecular surfaces, eF-seek; (iv) identification of sequence and structural neighbors; (v) a graphical user interface to all known protein folds with links to the above applications, Protein Globe. Recent examples are shown that highlight the utility of these tools in recognizing remote homologies between pairs of protein structures and in assigning putative biochemical functions to newly determined targets from structural genomics projects.

post to: CiteULike

IMGT, a system and an ontology that bridge biological and computational spheres in bioinformatics.

Publication Date: 2008 Apr 19 PMID: 18424816
Authors: Marie-Paule, L. - Giudicelli, V. - Regnier, L. - Duroux, P.
Journal: Brief Bioinform

IMGT(R), the international ImMunoGeneTics information system (http://imgt.cines.fr), is the reference in immunogenetics and immunoinformatics. IMGT standardizes and manages the complex immunogenetic data that include the immunoglobulins (IG) or antibodies, the T cell receptors (TR), the major histocompatibility complex (MHC) and the related proteins of the immune system (RPI), which belong to the immunoglobulin superfamily (IgSF) and the MHC superfamily (MhcSF). The accuracy and consistency of IMGT data and the coherence between the different IMGT components (databases, tools and Web resources) are based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets relying on seven axioms, 'IDENTIFICATION', 'DESCRIPTION', 'CLASSIFICATION', 'NUMEROTATION', 'LOCALIZATION', 'ORIENTATION' and 'OBTENTION', that postulate that objects, processes and relations have to be identified, described, classified, numerotated, localized, orientated, and that the way they are obtained has to be determined. These axioms constitute the Formal IMGT-ONTOLOGY, also designated as IMGT-Kaleidoscope. These axioms have been essential for the conceptualization of the molecular immunogenetics knowledge and for the creation of IMGT. Indeed all the components of the IMGT integrated system have been developed, based on standardized concepts and relations, thus allowing IMGT to bridge biological and computational spheres in bioinformatics. The same axioms can be used to generate concepts for multi-scale level approaches at the molecule, cell, tissue, organ, organism or population level, emphasizing the generalization of the application domain. In that way the Formal IMGT-ONTOLOGY represents a paradigm for the elaboration of ontologies in system biology.

post to: CiteULike

The relative value of operon predictions.

Publication Date: 2008 Apr 17 PMID: 18420711
Authors: Brouwer, R. W. - Kuipers, O. P. - Hijum, S. A.
Journal: Brief Bioinform

For most organisms, computational operon predictions are the only source of genome-wide operon information. Operon prediction methods described in literature are based on (a combination of) the following five criteria: (i) intergenic distance, (ii) conserved gene clusters, (iii) functional relation, (iv) sequence elements and (v) experimental evidence. The performance estimates of operon predictions reported in literature cannot directly be compared due to differences in methods and data used in these studies. Here, we survey the current status of operon prediction methods. Based on a comparison of the performance of operon predictions on Escherichia coli and Bacillus subtilis we conclude that there is still room for improvement. We expect that existing and newly generated genomics and transcriptomics data will further improve accuracy of operon prediction methods.

post to: CiteULike

MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences.

Publication Date: 2008 Apr 16 PMID: 18417537
Authors: Kumar, S. - Nei, M. - Dudley, J. - Tamura, K.
Journal: Brief Bioinform

The Molecular Evolutionary Genetics Analysis (MEGA) software is a desktop application designed for comparative analysis of homologous gene sequences either from multigene families or from different species with a special emphasis on inferring evolutionary relationships and patterns of DNA and protein evolution. In addition to the tools for statistical analysis of data, MEGA provides many convenient facilities for the assembly of sequence data sets from files or web-based repositories, and it includes tools for visual presentation of the results obtained in the form of interactive phylogenetic trees and evolutionary distance matrices. Here we discuss the motivation, design principles and priorities that have shaped the development of MEGA. We also discuss how MEGA might evolve in the future to assist researchers in their growing need to analyze large data set using new computational methods.

post to: CiteULike

Pfam 10 years on: 10,000 families and still growing.

Publication Date: 2008 May PMID: 18344544
Authors: Sammut, S. J. - Finn, R. D. - Bateman, A.
Journal: Brief Bioinform

Classifications of proteins into groups of related sequences are in some respects like a periodic table for biology, allowing us to understand the underlying molecular biology of any organism. Pfam is a large collection of protein domains and families. Its scientific goal is to provide a complete and accurate classification of protein families and domains. The next release of the database will contain over 10,000 entries, which leads us to reflect on how far we are from completing this work. Currently Pfam matches 72% of known protein sequences, but for proteins with known structure Pfam matches 95%, which we believe represents the likely upper bound. Based on our analysis a further 28,000 families would be required to achieve this level of coverage for the current sequence database. We also show that as more sequences are added to the sequence databases the fraction of sequences that Pfam matches is reduced, suggesting that continued addition of new families is essential to maintain its relevance.

post to: CiteULike

A review of bioinformatics education in Germany.

Publication Date: 2008 May PMID: 18310676
Authors: Koch, I. - Fuellen, G.
Journal: Brief Bioinform

We describe the establishment of bioinformatics in Germany and give an overview of current bioinformatics education in this country, from the perspective of the practitioner. The aim of this study is to demonstrate development of a strong bioinformatics education at German universities and research institutes during the last years. Beginning with a definition of the multi-disciplinary field bioinformatics, we give a survey of government initiatives in Germany in support of this field, which resulted in a wide spectrum of courses. To the best of our knowledge, we compile all ongoing courses at universities and research institutes. Five case studies featuring university courses with different educational focus illustrate the variety of efforts. In this context we also discuss the main components of German bioinformatics curricula. These components can be considered as the basic knowledge of German bioinformaticians. We conclude by giving perspectives for further development of bioinformatics education.

post to: CiteULike

Interoperability with Moby 1.0--it's better than sharing your toothbrush!

Publication Date: 2008 May PMID: 18238804
Authors: Wilkinson, M. D. - Senger, M. - Kawas, E. - Bruskiewich, R. - Gouzy, J. - Noirot, C. - Bardou, P. - Ng, A. - Haase, D. - Saiz Ede, A. - Wang, D. - Gibbons, F. - Gordon, P. M. - Sensen, C. W. - Carrasco, J. M. - Fernandez, J. M. - Shen, L. - Links, M. - Ng, M. - Opushneva, N. - Neerincx, P. B. - Leunissen, J. A. - Ernst, R. - Twigger, S. - Usadel, B. - Good, B. - Wong, Y. - Stein, L. - Crosby, W. - Karlsson, J. - Royo, R. - Parraga, I. - Ramirez, S. - Gelpi, J. L. - Trelles, O. - Pisano, D. G. - Jimenez, N. - Kerhornou, A. - Rosset, R. - Zamacola, L. - Tarraga, J. - Huerta-Cepas, J. - Carazo, J. M. - Dopazo, J. - Guigo, R. - Navarro, A. - Orozco, M. - Valencia, A. - Claros, M. G. - Perez, A. J. - Aldana, J. - Rojano, M. M. - Fernandez-Santa Cruz, R. - Navas, I. - Schiltz, G. - Farmer, A. - Gessler, D. - Schoof, H. - Groscurth, A.
Journal: Brief Bioinform

The BioMoby project was initiated in 2001 from within the model organism database community. It aimed to standardize methodologies to facilitate information exchange and access to analytical resources, using a consensus driven approach. Six years later, the BioMoby development community is pleased to announce the release of the 1.0 version of the interoperability framework, registry Application Programming Interface and supporting Perl and Java code-bases. Together, these provide interoperable access to over 1400 bioinformatics resources worldwide through the BioMoby platform, and this number continues to grow. Here we highlight and discuss the features of BioMoby that make it distinct from other Semantic Web Service and interoperability initiatives, and that have been instrumental to its deployment and use by a wide community of bioinformatics service providers. The standard, client software, and supporting code libraries are all freely available at http://www.biomoby.org/.

post to: CiteULike

The BREW workshop series: a stimulating experience in PhD education.

Publication Date: 2008 May PMID: 18216087
Authors: Giegerich, R. - Brazma, A. - Jonassen, I. - Ukkonen, E. - Vingron, M.
Journal: Brief Bioinform

Over recent years, five European PhD programmes have organized a series of 'Bioinformatics Research and Education Workshops'. These workshops address the needs of first-year PhD students and have been designed to combine a maximum of educational impact and scientific stimulation with a minimum of financial and administrative effort. We describe the BREW experience and argue that this type of event constitutes an attractive component of PhD education in computational biology and beyond.

post to: CiteULike

Gene-set approach for expression pattern analysis.

Publication Date: 2008 May PMID: 18202032
Authors: Nam, D. - Kim, S. Y.
Journal: Brief Bioinform

Recently developed gene set analysis methods evaluate differential expression patterns of gene groups instead of those of individual genes. This approach especially targets gene groups whose constituents show subtle but coordinated expression changes, which might not be detected by the usual individual gene analysis. The approach has been quite successful in deriving new information from expression data, and a number of methods and tools have been developed intensively in recent years. We review those methods and currently available tools, classify them according to the statistical methods employed, and discuss their pros and cons. We also discuss several interesting extensions to the methods.

post to: CiteULike

Two interactive Bioinformatics courses at the Bielefeld University Bioinformatics Server.

Publication Date: 2008 May PMID: 18199576
Authors: Sczyrba, A. - Konermann, S. - Giegerich, R.
Journal: Brief Bioinform

Conferences in computational biology continue to provide tutorials on classical and new methods in the field. This can be taken as an indicator that education is still a bottleneck in our field's process of becoming an established scientific discipline. Bielefeld University has been one of the early providers of bioinformatics education, both locally and via the internet. The Bielefeld Bioinformatics Server (BiBiServ) offers a variety of older and new materials. Here, we report on two online courses made available recently, one introductory and one on the advanced level: (i) SADR: Sequence Analysis with Distributed Resources (http://bibiserv.techfak.uni-bielefeld.de/sadr/) and (ii) ADP: Algebraic Dynamic Programming in Bioinformatics (http://bibiserv.techfak.uni-bielefeld.de/dpcourse/).

post to: CiteULike

ROC analysis: applications to the classification of biological sequences and 3D structures.

Publication Date: 2008 May PMID: 18192302
Authors: Sonego, P. - Kocsor, A. - Pongor, S.
Journal: Brief Bioinform

ROC ('receiver operator characteristics') analysis is a visual as well as numerical method used for assessing the performance of classification algorithms, such as those used for predicting structures and functions from sequence data. This review summarizes the fundamental concepts of ROC analysis and the interpretation of results using examples of sequence and structure comparison. We overview the available programs and provide evaluation guidelines for genomic/proteomic data, with particular regard to applications to large and heterogeneous databases used in bioinformatics.

post to: CiteULike