Briefings in Functional Genomics and Proteomics

Publications in this journal

• Article: Apoptotic blocks and chemotherapy resistance: strategies to identify Bcl-2 protein signatures.

  Ozgur Gul, Huveyda Basaga, Ozgur Kutuk
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  ABSTRACT: Acquired or innate resistance to chemotherapy is a major drawback of cancer therapeutics, which is frequently seen in epithelial cancers. However, the molecular mechanisms underlying chemotherapy resistance remain poorly understood. The mitochondrial pathway is a critical death pathway common to many different types of chemotherapy. Aberrations in this pathway can result in resistance to chemotherapy. The Bcl-2 family of proteins control commitment to programmed cell death by mitochondrial apoptosis. In this review, we will summarize the strategies in determining the components of apoptotic defects responsible for chemotherapy resistance, mainly focused on Bcl-2 protein network.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):27-34.
• Article: Proteogenomics: needs and roles to be filled by proteomics in genome annotation.

  Charles Ansong, Samuel O Purvine, Joshua N Adkins, Mary S Lipton, Richard D Smith
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  ABSTRACT: While genome sequencing efforts reveal the basic building blocks of life, a genome sequence alone is insufficient for elucidating biological function. Genome annotation--the process of identifying genes and assigning function to each gene in a genome sequence--provides the means to elucidate biological function from sequence. Current state-of-the-art high-throughput genome annotation uses a combination of comparative (sequence similarity data) and non-comparative (ab initio gene prediction algorithms) methods to identify protein-coding genes in genome sequences. Because approaches used to validate the presence of predicted protein-coding genes are typically based on expressed RNA sequences, they cannot independently and unequivocally determine whether a predicted protein-coding gene is translated into a protein. With the ability to directly measure peptides arising from expressed proteins, high-throughput liquid chromatography-tandem mass spectrometry-based proteomics approaches can be used to verify coding regions of a genomic sequence. Here, we highlight several ways in which high-throughput tandem mass spectrometry-based proteomics can improve the quality of genome annotations and suggest that it could be efficiently applied during the gene calling process so that the improvements are propagated through the subsequent functional annotation process.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):50-62.
• Article: The prediction of protein subcellular localization from sequence: a shortcut to functional genome annotation.

  Rita Casadio, Pier Luigi Martelli, Andrea Pierleoni
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  ABSTRACT: Automated sequence annotation is a major goal of post-genomic era with hundreds of genomes in the databases, from both prokaryotes and eukaryotes. While the number of fully sequenced chromosomes from microbial organisms exponentially increased in the last decade above 600, presently we know the whole DNA content of only 25 eukaryotic organisms, including Homo sapiens. However, the process of genome annotation is far from being completed. This is particularly relevant in eukaryotes, whose cells contain several subcellular compartments, or organelles, enclosed by membranes, where different relevant functions are performed. Translocation across the membrane into the organelles is a highly regulated and complex cellular process. Indeed different proteins and/or protein isoforms, originated from genes by alternative splicing, may be conveyed to different cell compartments, depending on their specific role in the cell. During recent years the prediction of subcellular localization (SL) by computational means has been an active research area. Several methods are presently available based on different notions and addressing different aspects of SL. This review provides a short overview of the most well performing methods described in the literature, highlighting their predictive capabilities and different applications.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):63-73.
• Article: Directional and quantitative phosphorylation networks.

  Claus Jørgensen, Rune Linding
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  ABSTRACT: Directionality in protein signalling networks is due to modulated protein-protein interactions and is fundamental for proper signal progression and response to external and internal cues. This property is in part enabled by linear motifs embedding post-translational modification sites. These serve as recognition sites, guiding phosphorylation by kinases and subsequent binding of modular domains (e.g. SH2 and BRCT). Characterization of such modification-modulated interactions on a proteome-wide scale requires extensive computational and experimental analysis. Here, we review the latest advances in methods for unravelling phosphorylation-mediated cellular interaction networks. In particular, we will discuss how the combination of new quantitative mass-spectrometric technologies and computational algorithms together are enhancing mapping of these largely uncharted dynamic networks. By combining quantitative measurements of phosphorylation events with computational approaches, we argue that systems level models will help to decipher complex diseases through the ability to predict cellular systems trajectories.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):17-26.
• Article: Profiling killers; unravelling the pathways of human natural killer cell function.

  Gina B Scott, Josephine L Meade, Graham P Cook
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  ABSTRACT: Natural killer (NK) cells are lymphocytes with an innate ability to recognize and kill infected cells and tumour cells. Unlike B and T cells, NK cells do not express an antigen receptor. Instead, NK cells detect changes in the phenotype of the target cell surface; malignant transformation or infection resulting in the loss or gain of particular molecules that are detected by inhibitory or activating receptors on the NK cell surface. The identification and characterization of NK cells and their receptors was made possible by monoclonal antibody technology. The ease with which genes and gene products can now be identified and manipulated has accelerated our understanding of NK cell function. Furthermore, gene and protein profiling studies are beginning to refine our understanding of NK cells, their interactions with other cells and their effector mechanisms. This review illustrates some of the basic features of NK cell biology and highlights the contribution made by post-genomic technology in defining the molecular mechanisms by which NK cells identify and kill susceptible targets.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):8-16.
• Article: Functional genomics in translational cancer research: focus on breast cancer.

  Isik G Yulug, Bala Gur-Dedeoglu
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  ABSTRACT: Conventional molecular and genetic methods for studying cancer are limited to the analysis of one locus at a time. A cluster of genes that are regulated together can be identified by DNA microarray, and the functional relationships can uncover new aspects of cancer biology. Breast cancer can be used to provide a model to demonstrate the current approaches to the molecular analysis of cancer. Meta-analysis is an important tool for the identification and validation of differentially expressed genes to increase power in clinical and biological studies across different sets of data. Recently, meta-analysis approaches have been applied to large collections of microarray datasets to investigate molecular commonalities of multiple cancer types not only to find the common molecular pathways in tumour development but also to compare the individual datasets to other cancer datasets to identify new sets of genes. Several investigators agree that microarray results should be validated. One commonly used method is quantitative reverse transcription PCR (qRT-PCR) to validate the expression profiles of the target genes obtained through microarray experiments. qRT-PCR is attractive for clinical use, since it can be automated and performed on fresh or archived formalin-fixed, paraffin-embedded tissue samples. The outcome of these analyses might accelerate the application of basic research findings into daily clinical practice through translational research and may have an impact on foreseeing the clinical outcome, predicting tumour response to specific therapy, identification of new prognostic biomarkers, discovering targets for the development of novel therapies and providing further insights into tumour biology.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):1-7.
• Article: Mass spectrometry is only one piece of the puzzle in clinical proteomics.

  James N McGuire, Julie Overgaard, Flemming Pociot
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  ABSTRACT: Biomarker discovery in clinical proteomics is being performed on relatively large patient cohorts by utilizing the high throughput of laser desorption/ionization mass spectrometry (MALDI- and SELDI-TOF-MS). Dealing directly with patient samples as opposed to working in cell or animal systems requires a host of considerations both before and after mass spectrometric analysis to obtain robust biomarker candidates. The challenges associated with the heterogeneity of typical samples are amplified by the ability to detect hundreds to thousands of proteins simultaneously. Adherence to protocols and consistency, however, can ensure optimal results. A study starts necessarily with a relevant clinical question and proceeds to a planning phase where sample availability, statistical test selection, logistics and bias reduction are key points. The physical analysis requires consistency and standardized protocols that are helped significantly through automation. Data analysis is broken into two stages, screening and final testing, which can detect either single candidates or a pattern of proteins. Biomarker identification can be performed at this point and will help significantly in the last stage, interpretation. Replication should be performed in an independent sample set in a separate study. The candidate biomarkers from an initial study give a wealth of information that can help to pinpoint patient subpopulations for a more exhaustive proteomic study using complementary platforms with limited capacity but extremely high information content. A clinical proteomics pilot project can also lead to better selection of model systems by providing a direct link with patient samples.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):74-83.
• Article: The plasma proteome, adductome and idiosyncratic toxicity in toxicoproteomics research.

  B Alex Merrick
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  ABSTRACT: Toxicoproteomics uses the discovery potential of proteomics in toxicology research by applying global protein measurement technologies to biofluids and tissues after host exposure to injurious agents. Toxicoproteomic studies thus far have focused on protein profiling of major organs and biofluids such as liver and blood in preclinical species exposed to model toxicants. The slow pace of discovery for new biomarkers, toxicity signatures and mechanistic insights is partially due to the limited proteome coverage derived from analysis of native organs, tissues and body fluids by traditional proteomic platforms. Improved toxicoproteomic analysis would result by combining higher data density LC-MS/MS platforms with stable isotope labelled peptides and parallel use of complementary platforms. Study designs that remove abundant proteins from biofluids, enrich subcellular structures and include cell specific isolation from heterogeneous tissues would greatly increase differential expression capabilities. By leveraging resources from immunology, cell biology and nutrition research communities, toxicoproteomics could make particular contributions in three inter-related areas to advance mechanistic insights and biomarker development: the plasma proteome and circulating microparticles, the adductome and idiosyncratic toxicity.
  Briefings in Functional Genomics and Proteomics 02/2008; 7(1):35-49.
• Article: A proteomic approach to iron and copper homeostasis in cyanobacteria.

  Berta De la Cerda, Ornella Castielli, Raúl V Durán, José A Navarro, Manuel Hervás, Miguel A De la Rosa
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  ABSTRACT: Cyanobacteria, which are considered to be the chloroplast precursors, are significant contributors to global photosynthetic productivity. The ample variety of membrane and soluble proteins containing different metals (mainly, iron and copper) has made these organisms develop a complex homeostasis with different mechanisms and tight regulation processes to fulfil their metal requirements in a changing environment. Cell metabolism is so adapted as to synthesize alternative proteins depending on the relative metal availabilities. In particular, plastocyanin, a copper protein, and cytochrome c(6), a haem protein, can replace each other to play the same physiological role as electron carriers in photosynthesis and respiration, with the synthesis of one protein or another being regulated by copper concentration in the medium. The unicellular cyanobacterium Synechocystis sp. PCC 6803 has been widely used as a model system because of completion of its genome sequence and the ease of its genetic manipulation, with a lot of proteomic work being done. In this review article, we focus on the functional characterization of knockout Synechocystis mutants for plastocyanin and cytochrome c(6), and discuss the ongoing proteomic analyses performed at varying copper concentrations to investigate the cyanobacterial metal homeostasis and cell response to changing environmental conditions.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):322-9.
• Article: Genomics of mRNA turnover.

  José E Pérez-Ortín
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  ABSTRACT: Most studies on eukaryotic gene regulation have focused on mature mRNA levels. Nevertheless, the steady-state mRNA level is the result of two opposing biological processes: transcription and degradation, both of which can be important points to regulate gene expression. It is now possible to determine the transcription and degradation rates (TR and DR), as well as the mRNA amount, for each gene using DNA chip technologies. In this way, each individual contribution to gene expression can be analysed. This review will deal with the techniques used for the genomic evaluation of TR and DR developed for the yeast Saccharomyces cerevisiae. They will be described in detail and their potential drawbacks discussed. I will also discuss the integration of the data obtained to fully analyse the expression strategies used by yeast and other eukaryotic cells.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):282-91.
• Article: IG, TR and IgSF, MHC and MhcSF: what do we learn from the IMGT Colliers de Perles?

  Quentin Kaas, François Ehrenmann, Marie-Paule Lefranc
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  ABSTRACT: The immunoglobulin superfamily (IgSF) comprises the immunoglobulins (IG), T cell receptors (TR) and proteins that have the common feature of having at least one Ig-like domain. The major histocompatibility complex (MHC) superfamily (MhcSF) comprises, in addition to the MHC, proteins which share the common feature of having Mhc-like domains. IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr) has set up a unique numbering system and standardized 2D graphical representations, or IMGT Colliers de Perles, which take into account the structural features of the Ig-like and Mhc-like domains. In this article, we review the IMGT Scientific chart rules for the description of the IgSF (V and C types) and of the MhcSF (G type) domains. These rules are based on the IMGT-ONTOLOGY axioms and concepts and are applicable for the sequence and structure analysis, whatever the species, the IgSF or MhcSF protein, or the chain type. These IMGT Colliers de Perles are particularly useful for antibody engineering, sequence-structure analysis, visualization and comparison of positions for mutations, polymorphisms and contact analysis.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):253-64.
• Article: Improving yeast two-hybrid screening systems.

  Manfred Koegl, Peter Uetz
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  ABSTRACT: Yeast two-hybrid (Y2H) screening methods are an effective means for the detection of protein-protein interactions. Optimisation and automation has increased the throughput of the method to an extent that allows the systematic mapping of protein-protein interactions on a proteome-wide scale. Since two-hybrid screens fail to detect a great number of interactions, parallel high-throughput approaches are needed for proteome-wide interaction screens. In this review, we discuss and compare different approaches for adaptation of Y2H screening to high-throughput, the limits of the method and possible alternative approaches to complement the mapping of organism-wide protein-protein interactions.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):302-12.
• Article: Molecular approaches in pig breeding to improve meat quality.

  Roberta Davoli, Silvia Braglia
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  ABSTRACT: This article reviews the advances in molecular genetics that have led to the identification of genes and markers associated with meat quality in pig. The development of a considerable number of annotated livestock genome sequences represents an incredibly rich source of information that can be used to identify candidate genes responsible for complex traits and quantitative trait loci effects. In pig, the huge amount of information emerging from the study of the genome has helped in the acquisition of new knowledge concerning biological systems and it is opening new opportunities for the genetic selection of this specie. Among the new fields of genomics recently developed, functional genomics and proteomics that allow considering many genes and proteins at the same time are very useful tools for a better understanding of the function and regulation of genes, and how these participate in complex networks controlling the phenotypic characteristics of a trait. In particular, global gene expression profiling at the mRNA and protein level can provide a better understanding of gene regulation that underlies biological functions and physiology related to the delivery of a better pig meat quality. Moreover, the possibility to realize an integrated approach of genomics and proteomics with bioinformatics tools is essential to obtain a complete exploitation of the available molecular genetics information. The development of this knowledge will benefit scientists, industry and breeders considering that the efficiency and accuracy of the traditional pig selection schemes will be improved by the implementation of molecular data into breeding programs.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):313-21.
• Article: Phenobabelomics--mouse phenotype data resources.

  John M Hancock, Ann-Marie Mallon
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  ABSTRACT: An essential aspect to understanding the functional significance of individual genes in the mouse genome is an understanding of the phenotypic consequences of gene mutations. A wide variety of online sites exist that provide different types of phenotypic information on the laboratory mouse. In this review, we describe the major resources that are currently available and discuss some of the bioinformatics requirements that will be necessary to make more seamless searching, comparison and analysis of these various data types possible.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):292-301.
• Article: Microarray data analysis and mining approaches.

  Francesca Cordero, Marco Botta, Raffaele A Calogero
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  ABSTRACT: Microarray based transcription profiling is now a consolidated methodology and has widespread use in areas such as pharmacogenomics, diagnostics and drug target identification. Large-scale microarray studies are also becoming crucial to a new way of conceiving experimental biology. A main issue in microarray transcription profiling is data analysis and mining. When microarrays became a methodology of general use, considerable effort was made to produce algorithms and methods for the identification of differentially expressed genes. More recently, the focus has switched to algorithms and database development for microarray data mining. Furthermore, the evolution of microarray technology is allowing researchers to grasp the regulative nature of transcription, integrating basic expression analysis with mRNA characteristics, i.e. exon-based arrays, and with DNA characteristics, i.e. comparative genomic hybridization, single nucleotide polymorphism, tiling and promoter structure. In this article, we will review approaches used to detect differentially expressed genes and to link differential expression to specific biological functions.
  Briefings in Functional Genomics and Proteomics 01/2008; 6(4):265-81.
• Article: Transcriptomics resources for functional genomics.

  Jun Kawai, Piero Carninci, Yoshihide Hayashizaki
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  ABSTRACT: For the past decade, extensive efforts have been made for establishing cDNA clone resources for various species. The most striking breakthrough has been full-length cDNA technology allowing cloning of intact RNA molecules as cDNA. These transcriptomics resources are providing researchers with essential tools for studies of functional genomics. Here, the importance of quality and availability of these resources is discussed.
  Briefings in Functional Genomics and Proteomics 10/2007; 6(3):171-9.
• Article: Resources, standards and tools for systems biology.

  Christoph Wierling, Ralf Herwig, Hans Lehrach
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  ABSTRACT: Modelling and simulation techniques are valuable tools for the understanding of complex biological systems. The design of a computer model necessarily has many diverse inputs, such as information on the model topology, reaction kinetics and experimental data, derived either from the literature, databases or direct experimental investigation. In this review, we describe different data resources, standards and modelling and simulation tools that are relevant to integrative systems biology.
  Briefings in Functional Genomics and Proteomics 10/2007; 6(3):240-51.
• Article: Development and perspectives of scientific services offered by genomic biological resource centres.

  Florian Wagner, Karsten R Heidtke, Bernd Drescher, Uwe Radelof
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  ABSTRACT: A number of fundamental technical developments like the evolvement of oligonucleotide microarrays, new sequencing technologies and gene synthesis have considerably changed the character of genomic biological resource centres in recent years. While genomic biological resource centres traditionally served mainly as providers of sparsely characterized cDNA clones and clone sets, there is nowadays a clear tendency towards well-characterized, high-quality clones. In addition, major new service units like microarray services have developed, which are completely independent of clone collections, reflecting the co-evolution of data generation and technology development. The new technologies require an increasingly higher degree of specialization, data integration and quality standards. Altogether, these developments result in spin-offs of highly specialized biotech companies, some of which will take a prominent position in translational medicine.
  Briefings in Functional Genomics and Proteomics 10/2007; 6(3):163-70.
• Article: EMMA--the European mouse mutant archive.

  Michael Hagn, Susan Marschall, Martin Hrabè de Angelis
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  ABSTRACT: The European Mouse Mutant Archive (EMMA) offers the worldwide scientific community a free archiving service for its mutant mouse lines and access to a wide range of disease models and other research tools. EMMA is currently comprised of seven partners who operate as the primary mouse repository in Europe. EMMA' s primary objectives are to establish and manage a unified repository for maintaining mouse mutations and to make them available to the scientific community. In addition to these core services, the consortium can generate germ-free (axenic) mice for its customers and also hosts courses in cryopreservation. EMMA is a founder member of the Federation of International Mouse Resources (FIMRe). The EMMA network is funded by the participating institutes, national research programmes and the European Commission Research Infrastructures Programme.
  Briefings in Functional Genomics and Proteomics 10/2007; 6(3):186-92.