Role of raf isoforms in signal transduction pathways relevant to leukemia cell proliferation

The invited commentary is addressed to the paper of Shelton et al published in this issue of Cell Cycle. The intracellular pathways that control cell growth constitute a complex nexus of signaling interactions that serve to regulate cell proliferation, differentiation and apoptosis. Dysregulation of these processes leads to the loss of control of cell growth that is characteristic of malignancy. Understanding cell signaling is a major challenge for modern biological research. One way to begin to unravel the intricate web of signaling pathways is to investigate the effects of mutant forms of key component proteins. One such protein is the serine/threonine-specific protein kinase, Raf.     

FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes

We present a simple but powerful procedure to extract Gene Ontology (GO) terms that are significantly over- or under-represented in sets of genes within the context of a genome-scale experiment (DNA microarray, proteomics, etc.). Said procedure has been implemented as a web application, FatiGO, allowing for easy and interactive querying. FatiGO, which takes the multiple-testing nature of statistical contrast into account, currently includes GO associations for diverse organisms (human, mouse, fly, worm and yeast) and the TrEMBL/Swissprot GOAnnotations@EBI correspondences from the European Bioinformatics Institute.     

Cells in experimental life sciences - challenges and solution to the rapid evolution of knowledge

Cell cultures used in biomedical experiments come in the form of both sample biopsy primary cells, and maintainable immortalised cell lineages. The rise of bioinformatics and high-throughput technologies has led us to the requirement of ontology representation of cell types and cell lines. The Cell Ontology (CL) and Cell Line Ontology (CLO) have long been established as reference ontologies in the OBO framework. We have compiled a series of the challenges and the proposals of solutions in this CELLS (Cells in ExperimentaL Life Sciences) thematic series that cover the grounds of standing issues and the directions, which were discussed in the First International Workshop on CELLS at the the International Conference on Biomedical Ontology (ICBO). This workshop focused on the extension of the current CL and CLO to cover a wider set of biological questions and challenges needing semantic infrastructure for information modeling. We discussed data-driven use cases that leverage linkage of CL, CLO and other bio-ontologies. This is an established approach in data-driven ontologies such as the Experimental Factor Ontology (EFO), and the Ontology for Biomedical Investigation (OBI). The First International Workshop on CELLS at the International Conference on Biomedical Ontology has brought together experimental biologists and biomedical ontologists to discuss solutions to organizing and representing the rapidly evolving knowledge gained from experimental cells. The workshop has successfully identified the areas of challenge, and the gap in connecting the two domains of knowledge. The outcome of this workshop yielded practical implementation plans to filled in this gap.This CELLS workshop also provided a venue for panel discussions of innovative solutions as well as challenges in the development and applications of biomedical ontologies to represent and analyze experimental cell data.     

GoSh: a web-based database for goat and sheep EST sequences

The GoSh database is a collection of 58 990 Capra hircus and Ovis aries expressed sequence tags. A perl pipeline was prepared to process sequences, and data were collected in a MySQL database. A PHP-based web interface allows browsing and querying the database. Putative single nucleotide polymorphism (SNP) detection, as well as search to repeats were performed, and links to external related resources were provided. Sequences were annotated against three different databases and an algorithm was implemented to create statistics of the distribution of retrieved homologous ontologies in the Gene Ontology categories. The GoSh database is a repository of data and links related to goat and sheep expressed genes. AVAILABILITY: The GoSh database is available at http://www.itb.cnr.it/gosh/     

The Most Outstanding Research of the Past Year

Cell Cycle acknowledges the most outstanding cell cycle research of the past year and presents the list of the top ten papers, published in all journals between 2002 and mid 2003. Papers were put forward by and final selections were made by members of the Cell Cycle Editorial Board. More than 40 papers were recommended. Criteria for selection were: the paper will affect future basic research or research in therapy or describes a new technology. This article introduces the authors, who describe the essence of their work.     

A Unified Anatomy Ontology of the Vertebrate Skeletal System

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.     

PRODISTIN Web Site: a tool for the functional classification of proteins from interaction networks

The PRODISTIN Web Site is a web service allowing users to functionally classify genes/proteins from any type of interaction network. The resulting computation provides a classification tree in which (1) genes/proteins are clustered according to the identity of their interaction partners and (2) functional classes are delineated in the tree using the Biological Process Gene Ontology annotations. AVAILABILITY: The PRODISTIN Web Site is freely accessible at http://gin.univ-mrs.fr/webdistin     

GOAnno: GO annotation based on multiple alignment

SUMMARY: GOAnno is a web tool that automatically annotates proteins according to the Gene Ontology (GO) using evolutionary information available in hierarchized multiple alignments. GO terms present in the aligned functional subfamily can be cross-validated and propagated to obtain highly reliable predicted GO annotation based on the GOAnno algorithm. AVAILABILITY: The web tool and a reduced version for local installation are freely available at http://igbmc.u-strasbg.fr/GOAnno/GOAnno.html SUPPLEMENTARY INFORMATION: The website supplies a detailed explanation and illustration of the algorithm at http://igbmc.u-strasbg.fr/GOAnno/GOAnnoHelp.html.     

RGMIMS: a web-based Laboratory Information Management System for plant functional genomics research

A robust Laboratory Information Management System (LIMS) is required for the efficient handling of data generated from large-scale insertional mutagenesis projects. The Rice Gene Machine Information Management System (RGMIMS), a web-based modular LIMS, developed in a rice functional genomics laboratory at CSIRO, currently has four core modules: Seed Management, Transformation Management, Plant/Progeny Management, Phenotype Management, and an ad hoc querying module. RGMIMS manages, preserves and tracks large inventories of transgenic germplasm and enables efficient and accurate record keeping of the large quantities of experimental data. RGMIMS automates and seamlessly integrates multi-step experimental processes. A web user interface, incorporating barcoding utilities, enables rapid data capture and tracking of biological resources. Ontologies from Gramene and Plant Ontology consortium are used to describe mutant phenotypes. RGMIMS supports generic research processes in plant mutagenesis and could readily be adapted to general LIMS for high-throughput plant research.     

An interview with Dr. John J. Tyson on his highly cited paper published in Cell Cycle

Comment on: Steady states and oscillations in the p53/Mdm2 network.

Ciliberto A, et al. Cell Cycle 2005; 4:488-93.     

An improved ontological representation of dendritic cells as a paradigm for all cell types

Background  

Recent increases in the volume and diversity of life science data and information and an increasing emphasis on data sharing and interoperability have resulted in the creation of a large number of biological ontologies, including the Cell Ontology (CL), designed to provide a standardized representation of cell types for data annotation. Ontologies have been shown to have significant benefits for computational analyses of large data sets and for automated reasoning applications, leading to organized attempts to improve the structure and formal rigor of ontologies to better support computation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL's utility for computation and for cross-species data integration.     

The semantic metadatabase (SEMEDA): ontology based integration of federated molecular biological data sources

A system for "intelligent" semantic integration and querying of federated databases is being implemented by using three main components: A component which enables SQL access to integrated databases by database federation (MARGBench), an ontology based semantic metadatabase (SEMEDA) and an ontology based query interface (SEMEDA-query). In this publication we explain and demonstrate the principles, architecture and the use of SEMEDA. Since SEMEDA is implemented as 3 tiered web application database providers can enter all relevant semantic and technical information about their databases by themselves via a web browser. SEMEDA' s collaborative ontology editing feature is not restricted to database integration, and might also be useful for ongoing ontology developments, such as the "Gene Ontology" [2]. SEMEDA can be found at http://www-bm.cs.uni-magdeburg.de/semeda/. We explain how this ontologically structured information can be used for semantic database integration. In addition, requirements to ontologies for molecular biological database integration are discussed and relevant existing ontologies are evaluated. We further discuss how ontologies and structured knowledge sources can be used in SEMEDA and whether they can be merged supplemented or updated to meet the requirements for semantic database integration.     

Dissecting the role of mTOR complexes in cellular senescence

Comment on: Kolesnichenko M, et al. Cell Cycle 2012; 11:2391-401. and Pospelova TV, et al. Cell Cycle 2012; 11:2402-407.     

POINeT: protein interactome with sub-network analysis and hub prioritization

Background  

Protein-protein interactions (PPIs) are critical to every aspect of biological processes. Expansion of all PPIs from a set of given queries often results in a complex PPI network lacking spatiotemporal consideration. Moreover, the reliability of available PPI resources, which consist of low- and high-throughput data, for network construction remains a significant challenge. Even though a number of software tools are available to facilitate PPI network analysis, an integrated tool is crucial to alleviate the burden on querying across multiple web servers and software tools.     

Dissecting the role of mTOR complexes in cellular senescence

Comment on: Kolesnichenko M, et al. Cell Cycle 2012; 11:2391-401. and Pospelova TV, et al. Cell Cycle 2012; 11:2402-407.     

Towards zoomable multidimensional maps of the cell

The detailed structure of molecular networks, including their dependence on conditions and time, are now routinely assayed by various experimental techniques. Visualization is a vital aid in integrating and interpreting such data. We describe emerging approaches for representing and visualizing systems data and for achieving semantic zooming, or changes in information density concordant with scale. A central challenge is to move beyond the display of a static network to visualizations of networks as a function of time, space and cell state, which capture the adaptability of the cell. We consider approaches for representing the role of protein complexes in the cell cycle, displaying modules of metabolism in a hierarchical format, integrating experimental interaction data with structured vocabularies such as Gene Ontology categories and representing conserved interactions among orthologous groups of genes.     

The Silicon Cell initiative: working towards a detailed kinetic description at the cellular level

The Silicon Cell initiative aims to understand cellular systems on the basis of the characteristics of their components. As a tool to achieve this, detailed kinetic models at the network reaction level are being constructed. Such detailed kinetic models are extremely useful for medical and biotechnological applications and form strong tools for fundamental studies. Several recently constructed detailed kinetic models on metabolism (glycolysis), signal transduction (EGF receptor), and the eukaryotic cell cycle (Saccharomyces cerevisiae) have been used to exemplify the Silicon Cell project. These models are stored and made accessible via the JWS Online Cellular Systems Modeling project, a web-based repository of kinetic models. Using a web-browser the models can be interrogated via a user-friendly graphical interface. The goal of the two projects is to combine models on parts of cellular systems and ultimately to construct detailed kinetic models at the cellular level.     

Interaction of TACC3 and TSC2 at the nuclear envelope and mitotic structures

Comment on: Gómez-Baldó L, et al. TACC3-TSC2 maintains nuclear envelope structure and controls cell division. Cell Cycle 2010; 9(6):In press.