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Results for “Functional Genomics”

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At least 91 records · Page 5Linked to original sources
PubMed2006

Using a standard framework for the phenotypic analysis of Medicago truncatula: an effective method for characterizing the plant material used for functional genomics approaches.

A crucial step for identifying genes of interest in legume crops is to determine gene function in Medicago truncatula. To facilitate functional genomics in this species, an ecophysiological framework of analysis was developed. Our primary aim was to establish a standard terminology for identifying each organ on the plant. A standard system for the characterization of the vegetative and the reproductive developmental stages was then proposed. Using these tools, the time course of vegetative development of nitrogen-fixing A17 plants was analysed in experiments conducted under different environmental conditions. To take into account the influence of temperature on plant development timing, an original approach was used by modelling vegetative development as a function of thermal time. Interestingly, the use of thermal time highlighted genotypic constants in plant development. Thereafter, to illustrate how this methodology can be used in explaining phenotypic alterations, the phenotype of two allelic mutants was analysed. Because the tools proposed in this paper allow the following: (1) standardization of how the plant material should be characterized to be used for functional genomics; (2) prediction of plant vegetative development; and (3) a more accurate phenotyping, the use of these tools by the M. truncatula community should provide a relevant framework for facilitating the production of reproducible functional genomics data.

Alleles↗
PubMed2005

Application of metabolome data in functional genomics: a conceptual strategy.

A gene with yet unknown physiological function can be studied by changing its expression level followed by analysis of the resulting phenotype. This type of functional genomics study can be complicated by the occurrence of 'silent mutations', the phenotypes of which are not easily observable in terms of metabolic fluxes (e.g., the growth rate). Nevertheless, genetic alteration may give rise to significant yet complicated changes in the metabolome. We propose here a conceptual functional genomics strategy based on microbial metabolome data, which identifies changes in in vivo enzyme activities in the mutants. These predicted changes are used to formulate hypotheses to infer unknown gene functions. The required metabolome data can be obtained solely from high-throughput mass spectrometry analysis, which provides the following in vivo information: (1) the metabolite concentrations in the reference and the mutant strain; (2) the metabolic fluxes in both strains and (3) the enzyme kinetic parameters of the reference strain. We demonstrate in silico that changes in enzyme activities can be accurately predicted by this approach, even in 'silent mutants'.

Genome, Fungal↗
PubMed2004

Using functional genomics to improve productivity in the manufacture of industrial biochemicals.

Recent developments in the field of functional genomics have been used to increase productivity in the manufacture of industrial biochemicals. Technologies like transcriptomics and proteomics have profited from the increasing number of genome sequencing projects. Meanwhile functional genomics has evolved from several isolated technologies, such as DNA chip technology and proteomics, to combined approaches that can help us to understand why organisms produce a certain product. The combination of expression studies and kinetic studies, such as carbon flux determination or metabolite measurements, has significantly improved productivity in production processes.

Bacteria↗
PubMed2004

Functional genomics approach using mice.

The rapid development and characterization of the mouse genome sequence, coupled with comparative sequence analysis of human, has been paralleled by a reinforced enthusiasm for mouse functional genomics. The way to uncover the in vivo function of genes is to analyze the phenotypes of the mutant animals. From this standpoint, the mouse is a suitable and valuable model organism in the studies of functional genomics. Therefore, there have been enormous efforts to enrich the list of the mutant mice. Such a trend emphasizes the random mutagenesis, including ENU mutagenesis and gene-trap mutagenesis, to obtain a large stock of mutant mice. However, since various mutant alleles are needed to precisely characterize the role of a gene in vivo, mutations should be designed. The simplicity and utility of transgenic technology can satisfy this demand. The combination of RNA interference with transgenic technology will provide more opportunities for researchers. Nevertheless, gene targeting can solely define the in vivo function of a gene without a doubt. Thus, transgenesis and gene targeting will be the major strategies in the field of functional genomics.

Animals↗
PubMed2004

Functional genomics of osteoarthritis: on the way to evaluate disease hypotheses.

Functional genomics is a challenging new way to address complex diseases such as osteoarthritis on a molecular level. This complements previous research and will open up new areas of so far unrecognized molecular networks. In this respect, articular cartilage is a good target for functional genomics as it contains only one cell type to which all expression signals can be attributed to. Despite considerable limitations at present, such as a low sensitivity and insensitivity to alternative splicing, posttranscriptional regulation, and posttranslational modification, cDNA-array technology provides a powerful tool to obtain an overview on gene expression patterns hardly achievable with other techniques. This has been shown to be true for known genes as well as for the identification of new genes of interest. Therefore, gene expression analysis will help to identify single genes depending on the disease and experimental conditions investigated. However, the expression pattern of the plethora of expressed genes will paint a picture (network) of disease context, maybe even more pushing forward our understanding of complex diseases such as osteoarthritis.

Cartilage, Articular↗
PubMed2004

Flying through the genome: a comprehensive study of functional genomics using RNAi in Drosophila.

Sequencing the DNA of an entire mammalian genome now seems routine. The human sequence along with the mouse--the model for mammalian genetics--and the rat--the model for mammalian physiology--are now part of the data archive. However, the real challenges for the 21st century are what to do with this information and how to test the function of so many different genes in so many different cellular contexts. The potential payoffs are enormous. Examples include a better understanding of disease pathologies with effective strategies for therapeutic interventions that cause few, if any, side effects.

Animals↗
PubMed2004

Functional genomics and insect chemical ecology.

High-throughput molecular techniques (i.e., genomics) are now beginning to make their way into chemical ecology research. Pioneering functional genomics studies have made significant contributions to our understanding of insect pheromone production, reception, behavior, and insect-plant interactions. Much of this research involves nonmodel organisms, including the honey bee, silkworm, and bark beetles, underscoring that researchers need not be restricted to traditional model organisms for high-throughput research. Furthermore, the technology can reveal physiological interactions that might otherwise be missed by more traditional molecular approaches. Functional genomics should become more widely used as researchers appreciate the wealth of information this potent approach can supply. This review concentrates on a summary of available technologies for functional genomics as they may be applied by chemical ecologists studying insects. Allied technologies (proteomics and metabolomics) are introduced briefly toward the end in the context of future applications.

Animals↗
PubMed2006

AgBase: a functional genomics resource for agriculture.

BACKGROUND: Many agricultural species and their pathogens have sequenced genomes and more are in progress. Agricultural species provide food, fiber, xenotransplant tissues, biopharmaceuticals and biomedical models. Moreover, many agricultural microorganisms are human zoonoses. However, systems biology from functional genomics data is hindered in agricultural species because agricultural genome sequences have relatively poor structural and functional annotation and agricultural research communities are smaller with limited funding compared to many model organism communities. DESCRIPTION: To facilitate systems biology in these traditionally agricultural species we have established "AgBase", a curated, web-accessible, public resource http://www.agbase.msstate.edu for structural and functional annotation of agricultural genomes. The AgBase database includes a suite of computational tools to use GO annotations. We use standardized nomenclature following the Human Genome Organization Gene Nomenclature guidelines and are currently functionally annotating chicken, cow and sheep gene products using the Gene Ontology (GO). The computational tools we have developed accept and batch process data derived from different public databases (with different accession codes), return all existing GO annotations, provide a list of products without GO annotation, identify potential orthologs, model functional genomics data using GO and assist proteomics analysis of ESTs and EST assemblies. Our journal database helps prevent redundant manual GO curation. We encourage and publicly acknowledge GO annotations from researchers and provide a service for researchers interested in GO and analysis of functional genomics data. CONCLUSION: The AgBase database is the first database dedicated to functional genomics and systems biology analysis for agriculturally important species and their pathogens. We use experimental data to improve structural annotation of genomes and to functionally characterize gene products. AgBase is also directly relevant for researchers in fields as diverse as agricultural production, cancer biology, biopharmaceuticals, human health and evolutionary biology. Moreover, the experimental methods and bioinformatics tools we provide are widely applicable to many other species including model organisms.

Agriculture↗
PubMedDate not supplied

Protein arrays in functional genome research.

Whole-genome analyses become more and more necessary for pharmaceutical research. DNA chip hybridizations are an important tool for monitoring gene expression profiles during diseases or medical treatment. However, drug target identification and validation as well as an increasing number of antibodies and other polypeptides tested as potential drugs produce an increasing demand for genome-wide functional assays. Protein arrays are an important step into this direction. Peptide arrays and protein expression libraries are useful for the identification of antibodies and for epitope mapping. Antibody arrays allow protein quantification, protein binding studies, and protein phosphorylation assays. Tissue micro-arrays give a detailed information about the localization of macromolecules. More complex interactions can be addressed in cells spotted in array format. Finally, microfluidics chips enable us to describe the communication between cells in a tissue. In this review, possibilities, limitations and chances of different protein array techniques are discussed.

Antibodies↗
PubMed2026

A practical guide to studying genome function using single-molecule genomics.

Single-molecule genomics (SMG) has transformed our ability to study the mechanisms that regulate the genome by enabling profiling of the activity of regulatory factors on individual DNA molecules genome-wide. SMG is able to quantify molecular heterogeneity and the co-occurrence of regulatory events, including epigenetic modifications, transcription factor binding and chromatin organization on single DNA molecules. SMG reveals dynamics of chromatin interactions that cannot be measured by conventional genomics assays. Therefore, SMG offers a unique platform to study how regulatory events combine to control genome activity. In this Expert Recommendation article, we provide a practical guide for adopting SMG and outline best practices.

Journal Article↗
PubMed2000

Metabolite profiling for plant functional genomics.

Multiparallel analyses of mRNA and proteins are central to today's functional genomics initiatives. We describe here the use of metabolite profiling as a new tool for a comparative display of gene function. It has the potential not only to provide deeper insight into complex regulatory processes but also to determine phenotype directly. Using gas chromatography/mass spectrometry (GC/MS), we automatically quantified 326 distinct compounds from Arabidopsis thaliana leaf extracts. It was possible to assign a chemical structure to approximately half of these compounds. Comparison of four Arabidopsis genotypes (two homozygous ecotypes and a mutant of each ecotype) showed that each genotype possesses a distinct metabolic profile. Data mining tools such as principal component analysis enabled the assignment of "metabolic phenotypes" using these large data sets. The metabolic phenotypes of the two ecotypes were more divergent than were the metabolic phenotypes of the single-loci mutant and their parental ecotypes. These results demonstrate the use of metabolite profiling as a tool to significantly extend and enhance the power of existing functional genomics approaches.

Arabidopsis↗
PubMed2004

Bordetella pertussis from functional genomics to intranasal vaccination.

Whooping cough still represents a major health problem, despite the use of effective vaccines for several decades. Being classically a typical childhood disease, whooping cough in young adults is now more common than it used to be, suggesting that protection after vaccination wanes during adolescence. As an alternative to the current vaccines, we wish to develop live attenuated vaccines to be delivered by the nasal route, such as to mimic the natural route of infection and to induce long lasting immunity. Bordetella pertussis, the etiological agent of whooping cough, produces a number of virulence factors, including toxins. Its recently determined genome sequence makes it now possible to apply functional genomics, such as transcriptomics and systematic knock-out mutagenesis. The expression of most known B. pertussis virulence genes is controlled by the two-component system BvgA/S. DNA microarray analyses have led to the identification of novel genes in the BvgA/S regulon, some of which are activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes appear to be differentially modulated by nicotinic acid and MgSO4, both known to modulate the expression of BvgA/S-regulated genes. Among others, the functional genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA and hotB (for 'homolog of toxin'), the products of which show high sequence similarities to pertussis toxin subunits. The identification of the full array of virulence factors, as well as an integrated understanding of the bacterial physiology should allow us to design attenuated B. pertussis strains useful for intranasal vaccination. A first generation of attenuated strains has already shown full protection in mice after a single intranasal administration. Such strains may also serve as vaccine carriers for heterologous antigens, in order to vaccinate against several different pathogens simultaneously.

Administration, Intranasal↗
PubMed2006

Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach.

At the 38th Annual Meeting of the Society for Leukocyte Biology held in Oxford this year, the biology of dendritic cells (DCs) and macrophages was discussed. In particular, functional genomics approaches were presented to investigate transcriptional changes during microbe and phagocytes interactions. Here, we report functional genomics studies likely to be of interest to the Journal of Leukocyte Biology readers with a particular emphasis on DC biology. DCs are professional antigen-presenting cells, which are essential for the initiation and regulation of natural killer, T, and T regulatory cell responses. Immature DCs, resident in peripheral sites, are specialized in antigen capture and continually sample soluble and particulate antigens in their local environment. DCs express receptors for cytokines, chemokines, endogenous danger signals, and microbial structures. The interactions between DCs and microorganism are complex, but progress in the past few years has shed light on several aspects of these processes. Infectious disease is the result of an intimate relationship between pathogens and hosts. Thus, understanding the cross-talk between host and pathogen is essential to improve our knowledge of infectious disease. Functional genomics and proteomics applied to DCs and macrophage biology are now providing powerful tools to dissect, at the molecular level, host-pathogen interactions.

Animals↗
PubMed2006

Yeast-based functional genomics and proteomics technologies: the first 15 years and beyond.

Yeast-based functional genomics and proteomics technologies developed over the past decade have contributed greatly to our understanding of bacterial, yeast, fly, worm, and human gene functions. In this review, we highlight some of these yeast-based functional genomic and proteomic technologies that are advancing the utility of yeast as a model organism in molecular biology and speculate on their future uses. Such technologies include use of the yeast deletion strain collection, large-scale determination of protein localization in vivo, synthetic genetic array analysis, variations of the yeast two-hybrid system, protein microarrays, and tandem affinity purification (TAP)-tagging approaches. The integration of these advances with established technologies is invaluable in the drive toward a comprehensive understanding of protein structure and function in the cellular milieu.

Forecasting↗
PubMed2004

An integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver.

In functional genomics, DNA microarrays for gene expression profiling are increasingly being used to provide insights into biological function or pathology. To better understand the significance of the multiple transcriptional changes across a time period, the temporal changes in phenotype must be described. Orotic acid-induced fatty liver disease was investigated at the transcriptional and metabolic levels using microarrays and metabolic profiling in two strains of rats. High-resolution 1H-NMR spectroscopic analysis of liver tissue indicated that Kyoto rats compared with Wistar rats are predisposed to the insult. Metabolite analysis and gene expression profiling following orotic acid treatment identified perturbed metabolic pathways, including those involved in fatty acid, triglyceride, and phospholipid synthesis, beta-oxidation, altered nucleotide, methyl donor, and carbohydrate metabolism, and stress responses. Multivariate analysis and statistical bootstrapping were used to investigate co-responses with transcripts involved in metabolism and stress responses. This reverse functional genomic strategy highlighted the relationship between changes in the transcription of stearoyl-CoA desaturase 1 and those of other lipid-related transcripts with changes in NMR-derived lipid profiles. The results suggest that the integration of 1H-NMR and gene expression data sets represents a robust method for identifying a focused line of research in a complex system.

Administration, Oral↗
PubMed2001

Evolution, language and analogy in functional genomics.

Almost a century ago, Wittgenstein pointed out that theory in science is intricately connected to language. This connection is not a frequent topic in the genomics literature. But a case can be made that functional genomics is today hindered by the paradoxes that Wittgenstein identified. If this is true, until these paradoxes are recognized and addressed, functional genomics will continue to be limited in its ability to extrapolate information from genomic sequences.

Amino Acid Sequence↗
PubMedDate not supplied

CDNAs for functional genomics and proteomics: the German Consortium.

To functionally characterize numerous novel proteins encoded by cDNAs sequenced by the German Consortium, 800 were tagged with green fluorescent protein. The subcellular localizations of the fusion proteins were examined in living cells, enabling their classification in subcellular groups. Their activity in cell growth, cell death, and protein transport was screened in high throughput using robotic liquid handling and reading stations. The resulting information is integrated with functional genomics and proteomics data for further understanding of protein functions in the cellular context.

DNA, Complementary↗