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At least 307 records · Page 17Linked to original sources
PubMed2006

Blast2GO goes grid: developing a grid-enabled prototype for functional genomics analysis.

The vast amount in complexity of data generated in Genomic Research implies that new dedicated and powerful computational tools need to be developed to meet their analysis requirements. Blast2GO (B2G) is a bioinformatics tool for Gene Ontology-based DNA or protein sequence annotation and function-based data mining. The application has been developed with the aim of affering an easy-to-use tool for functional genomics research. Typical B2G users are middle size genomics labs carrying out sequencing, ETS and microarray projects, handling datasets up to several thousand sequences. In the current version of B2G. The power and analytical potential of both annotation and function data-mining is somehow restricted to the computational power behind each particular installation. In order to be able to offer the possibility of an enhanced computational capacity within this bioinformatics application, a Grid component is being developed. A prototype has been conceived for the particular problem of speeding up the Blast searches to obtain fast results for large datasets. Many efforts have been done in the literature concerning the speeding up of Blast searches, but few of them deal with the use of large heterogeneous production Grid Infrastructures. These are the infrastructures that could reach the largest number of resources and the best load balancing for data access. The Grid Service under development will analyse requests based on the number of sequences, splitting them accordingly to the available resources. Lower-level computation will be performed through MPIBLAST. The software architecture is based on the WSRF standard.

Computational Biology↗
PubMed2001

The gene search system: its application to functional genomics in Drosophila melanogaster.

In Drosophila melanogaster, gain-of-function mutagenesis utilizing the GAL4-UAS system has been established, allowing identification of genes that may not be easily detectable by loss-of-function screening approaches. The conditional features of misexpression systems are especially useful for studying late-stage biological processes, such as those involving adult behavior or lifespan. The gene search system, incorporating a bidirectional misexpression vector, was used to screen for genes critical for longevity determination. We have identified several genes whose misexpression in adulthood extends the fly's lifespan. Phenotypic characterization of fly lines carrying a mis-expression vector, in conjunction with obtaining information about the genomic insertion sites, creates valuable resources for the systematic functional genomics in Drosophila.

Animals↗
PubMed2005

A functional genomics approach to hematopoietic stem cell regulation.

Elucidation of the molecular mechanisms that are responsible for regulating the most basic properties of stem cells, self-renewal, and differentiation remains a major challenge in hematopoietic stem cell biology. We have taken a functional genomics approach towards revealing these mechanisms. Previous studies of the fetal liver genetic program led to the development of Stem Cell Database (SCDb, http://stemcell.princeton.edu), a resource for the stem cell community. These studies have been expanded to include the microenvironmental component of hematopoiesis and are the focus herein. In our efforts to study the microenvironmental component we have identified a stromal cell line, AFT024, which serves as a surrogate stem cell niche. The line provides a milieu that facilitates the maintenance of transplantable mouse and human stem cells as well as the generation of large populations of committed progenitors. In a manner mirroring the work done with the SCDb, we provide an online resource, Stromal Cell Database, StroCDB (http://stromalcell.princeton.edu), that is a compendium of information and data derived from biological and molecular studies of this surrogate niche. These include bioinformatic analyses of over 6000 clones derived from a subtracted library enriched for messages expressed in AFT024 as well as data derived from custom expression arrays developed from this library. Herein we describe these efforts and provide a guide for navigating the database and mining the information contained within.

Animals↗
PubMed2003

Functional genomics guided with MR imaging: mouse tumor model study.

To gain a better understanding of gene expression patterns in tumors, the authors used contrast material-enhanced magnetic resonance (MR) imaging to noninvasively characterize regions within the same tumor to provide a correlate for genomic analysis. Gene expression profiles of samples from a mouse tumor model obtained from contrast-enhanced and nonenhanced regions within the same tumor were compared with MR imaging and functional genomics. From these samples, 11000 genes were analyzed: 10 genes were up-regulated in the contrast-enhanced areas, and one gene was up-regulated in the nonenhanced regions. Several of these genes encode extracellular matrix proteins. Findings in this study demonstrate that MR imaging can serve as a powerful noninvasive tool for characterizing different regions of tumors to guide genomic analysis with high spatial and temporal resolution.

Animals↗
PubMed2001

Convergent functional genomics: application to bipolar disorder.

The recent development of microarray technologies has made possible the simultaneous measurement of mRNA levels for thousands of genes and a new genomic method termed gene expression profiling. The application of this approach to animal models or post-mortem tissue provides a powerful tool for the discovery of novel genes involved in psychiatric disorders. This approach has strengths that are complementary to those of another genomic method for gene discovery, positional cloning. Microarray technologies and their application to post-mortem tissue and animal models of bipolar disorder are reviewed. A novel approach termed convergent functional genomics, which integrates gene profiling and positional cloning in order to rapidly identify candidate disease genes, is also described.

Amphetamine↗
PubMed2002

The functional genomics of CD14 and its role in IgE responses: an integrated view.

Several studies in recent years have suggested that there is a strong genetic component in the pathogenesis of IgE-mediated diseases. Epidemiologic studies have identified a number of genes that carry single base changes (single nucleotide polymorphisms) associated with parameters of allergy. What remain to be established are the mechanisms whereby genetic variation results in dysregulation of IgE-mediated responses. This is the task of functional genomics. In this article, some of the most powerful approaches that have been devised to provide a mechanistic explanation for the effects of genetic variation on the regulation of gene expression and function are discussed. Recent data on the impact of genetic variation on the regulation of CD14 are explored in the context of the potential role played by this gene in the pathogenesis of allergy. Also discussed is the notion that taken individually, each instance of variation might result in small effects. It is the combination of variations in the same gene and/or in genes arrayed along one functional pathway that might eventually lead to dysregulation strong enough to cause disease. In this scenario, the environment is likely to play an essential role in determining the functional outcome of genetic variation.

Gene Expression Regulation↗
PubMed1999

The University of Minnesota Biocatalysis/Biodegradation Database: specialized metabolism for functional genomics.

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://www.labmed.umn.edu/umbbd/i nde x.html) first became available on the web in 1995 to provide information on microbial biocatalytic reactions of, and biodegradation pathways for, organic chemical compounds, especially those produced by man. Its goal is to become a representative database of biodegradation, spanning the diversity of known microbial metabolic routes, organic functional groups, and environmental conditions under which biodegradation occurs. The database can be used to enhance understanding of basic biochemistry, biocatalysis leading to speciality chemical manufacture, and biodegradation of environmental pollutants. It is also a resource for functional genomics, since it contains information on enzymes and genes involved in specialized metabolism not found in intermediary metabolism databases, and thus can assist in assigning functions to genes homologous to such less common genes. With information on >400 reactions and compounds, it is poised to become a resource for prediction of microbial biodegradation pathways for compounds it does not contain, a process complementary to predicting the functions of new classes of microbial genes.

Bacteria↗
PubMed2005

Functional genomics, new tools in malaria research.

The mosquito-transmitted unicellular parasite Plasmodium falciparum, the agent of malaria disease, still causes more than one million deaths every year in the tropical and subtropical areas of the world. New intervention strategies are needed to contrast the insurgence of resistance to effective drugs and insecticides. The complete annotated genomes of the human parasite P. falciparum and the rodent model P. yoelii is now available thus providing a prediction of their possible gene products. This makes feasible the application of functional genomics to malaria research with the final goal of providing a complete survey of Plasmodium life cycle. Genome-wide approaches to the study of transcriptome or proteome were successfully applied to malaria parasite with the promise for new drug and vaccine candidates in the next future.

Animals↗
PubMed2006

Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms.

BACKGROUND: Expression of the Helicobacter pylori outer membrane protein HopH is regulated by phase variation within a CT dinucleotide repeat motif of the hopH gene. METHODS: To investigate the importance of HopH for bacterial pathogenicity, we performed a detailed functional genomic and population-based genetic characterization of this contingency locus. RESULTS: Sequencing of hopH in H. pylori strains from 58 patients revealed that the hopH "on" genotype is linked to bacterial virulence determinants, such as the vacAs1, vacAm1, babA2, and, most strongly, cagA genotypes. hopH mutagenesis resulted in reduced bacterial adherence to gastric epithelia in vitro. Complementation of hopH in trans restored the adherence properties of hopH mutants. Although HopH has been previously linked to proinflammatory epithelial signaling, hopH mutagenesis did not alter epithelial interleukin-8 secretion in vitro. Comparative epithelial gene-expression profiling by cDNA microarrays revealed no significant differences between the wild-type-specific and hopH mutant-specific transcriptomes. By contrast, a large set of genes was differentially regulated in a cag pathogenicity island-dependent manner. CONCLUSION: An in-frame hopH gene may be linked to gastroduodenal diseases because of its association with other virulence factors or increased bacterial adherence and colonization. The strong linkage with cagA indicates that HopH may contribute to the fitness of cagA-positive strains in vivo.

Adhesins, Bacterial↗
PubMed2025

Exploring phage-host interactions in Burkholderia cepacia complex bacterium to reveal host factors and phage resistance genes using CRISPRi functional genomics and transcriptomics.

Complex interactions of bacteriophages with their bacterial hosts determine phage host range and infectivity. While phage defense systems and host factors have been identified in model bacteria, they remain challenging to predict in non-model bacteria. In this paper, we integrate functional genomics and transcriptomics to investigate phage-host interactions, revealing active phage resistance and host factor genes in Burkholderia cenocepacia K56-2. Burkholderia cepacia complex species are commonly found in soil and are opportunistic pathogens in immunocompromised patients. We studied infection of B. cenocepacia K56-2 with Bcep176, a temperate phage isolated from Burkholderia multivorans. A genome-wide dCas9 knockdown library targeting B. cenocepacia K56-2 was constructed, and a pooled infection experiment identified 63 novel genes or operons coding for candidate host factors or phage resistance genes. The activities of a subset of candidate host factor and resistance genes were validated via single-gene knockdowns. Transcriptomics of B. cenocepacia K56-2 during Bcep176 infection revealed that expression of genes coding for host factor and resistance candidates identified in this screen was significantly altered during infection by 4 h post-infection. Identifying which bacterial genes are involved in phage infection is important to understand the ecological niches of B. cenocepacia and its phages, and for designing phage therapies.IMPORTANCEBurkholderia cepacia complex bacteria are opportunistic pathogens inherently resistant to antibiotics, and phage therapy is a promising alternative treatment for chronically infected patients. Burkholderia bacteria are also ubiquitous in soil microbiomes. To develop improved phage therapies for pathogenic Burkholderia bacteria, or engineer phages for applications, such as microbiome editing, it's essential to know the bacterial host factors required by the phage to kill bacteria, as well as how the bacteria prevent phage infection. This work identified 65 genes involved in phage-host interactions in Burkholderia cenocepacia K56-2 and tracked their expression during infection. These findings establish a knowledge base to select and engineer phages infecting or transducing Burkholderia bacteria.

Bacteriophages↗
PubMedDate not supplied

DNA microarray applications in functional genomics.

The successful completion of the Human Genome Project and the achievement of similar goals in other species have generated a huge amount of free available information about the genomic sequence of different organisms, opening the door to a postgenome era where new challenges arise. One of the most ambitious objectives of this new period, addressed by the emerging discipline of functional genomics, attempts to understand the genome and the products it encodes for, and how these gene products interact to produce complex living organisms. This new era is also characterized by the development of new technologies, which have produced genomic tools indispensable for understanding how gene products are regulated in normal and diseased conditions on a global genome scale. One of these technologies is DNA microarrays, turned into a very popular tool in the last years. Although the most common use of DNA microarrays is gene expression profiling, scientists have successfully used them for multiple applications, including genotyping, sequencing, DNA copy number analysis, and DNA-protein interactions, among others. In summary, DNA microarrays are changing the way biomedicine and other disciplines are addressing different biological questions and will allow the translation of genome research to the clinic.

Genomics↗
PubMed2004

Functional genomic analysis in pain research using hybridization arrays.

Hybridization array technology makes it possible to compare global gene-expression patterns in any experimental context for which good-quality RNA can be generated. To date, DNA arrays have been used as a tool to compare functional genomic changes (differences in wholesale gene expression) in studies that cover an impressive variety of research disciplines including cancer, yeast genomics, and, more recently, neuroscience and behavior. The basic premise of the array experiment is that one interrogates a panel of probes (gene-specific cDNA fragments or gene-specific oligonucleotides that have been immobilized on a solid support) with RNAs (targets) from control and treated experimental samples that have been either radioactively or fluorescently labeled. Signal derived from either competitive (both samples on a single chip) or differential (one sample/one chip) hybridization is used to calculate relative gene expression. There are three widely used platforms available to perform array experiments (Affymetrix GeneChips, oligonucleotide arrays, and membrane-based cDNA arrays) and each platform offers advantages and limitations. The experimental description in this chapter explains, in detail, how to perform a hybridization array using the macroarray platform.

Animals↗
PubMed2006

Wheat EST resources for functional genomics of abiotic stress.

BACKGROUND: Wheat is an excellent species to study freezing tolerance and other abiotic stresses. However, the sequence of the wheat genome has not been completely characterized due to its complexity and large size. To circumvent this obstacle and identify genes involved in cold acclimation and associated stresses, a large scale EST sequencing approach was undertaken by the Functional Genomics of Abiotic Stress (FGAS) project. RESULTS: We generated 73,521 quality-filtered ESTs from eleven cDNA libraries constructed from wheat plants exposed to various abiotic stresses and at different developmental stages. In addition, 196,041 ESTs for which tracefiles were available from the National Science Foundation wheat EST sequencing program and DuPont were also quality-filtered and used in the analysis. Clustering of the combined ESTs with d2_cluster and TGICL yielded a few large clusters containing several thousand ESTs that were refractory to routine clustering techniques. To resolve this problem, the sequence proximity and "bridges" were identified by an e-value distance graph to manually break clusters into smaller groups. Assembly of the resolved ESTs generated a 75,488 unique sequence set (31,580 contigs and 43,908 singletons/singlets). Digital expression analyses indicated that the FGAS dataset is enriched in stress-regulated genes compared to the other public datasets. Over 43% of the unique sequence set was annotated and classified into functional categories according to Gene Ontology. CONCLUSION: We have annotated 29,556 different sequences, an almost 5-fold increase in annotated sequences compared to the available wheat public databases. Digital expression analysis combined with gene annotation helped in the identification of several pathways associated with abiotic stress. The genomic resources and knowledge developed by this project will contribute to a better understanding of the different mechanisms that govern stress tolerance in wheat and other cereals.

Acclimatization↗
PubMed2002

Functional genomic analysis of type II IL-1beta decoy receptor: potential for gene therapy in human arthritis and inflammation.

Gene expression arrays show that human epithelial cells and human arthritis-affected cartilage lack detectable amounts of mRNA for IL-1 antagonizing molecules: IL-1Ra and IL-1RII, but constitutively express IL-1. Functional genomic analysis was performed by reconstituting human IL-1RII expression in various IL-1RII-deficient cell types to examine its antagonist role using gene therapy approaches. Adenovirus-expressing IL-1RII when transduced into human and bovine chondrocytes, human and rabbit synovial cells, human epithelial cells, and rodent fibroblasts expressed membrane IL-1RII and spontaneously released functional soluble IL-1RII. The IL-1RII(+) (but not IL-1RII(-)) cells were resistant to IL-1beta-induced, NO, PGE(2), IL-6, and IL-8 production or decreased proteoglycan synthesis. IL-1RII inhibited the function of IL-1 in chondrocytes and IL-1- and TNF-alpha-induced inflammatory mediators in human synovial and epithelial cells. IL-1RII(+) chondrocytes were more resistant to induction of NO and PGE(2) by IL-1beta compared with IL-1RII(-) cells incubated with a 10-fold (weight) excess of soluble type II IL-1R (sIL-1RII) protein. In cocultures, IL-1RII(+) synovial cells released sIL-1RII, which in a paracrine fashion protected chondrocytes from the effects of IL-1beta. Furthermore, IL-1RII(+) (but not IL-1RII(-)) chondrocytes when transplanted onto human osteoarthritis-affected cartilage in vitro, which showed spontaneous release of sIL-1RII for 20 days, inhibited the spontaneous production of NO and PGE(2) in cartilage in ex vivo. In summary, reconstitution of IL-1RII in IL-1RII(-) cells using gene therapy approaches significantly protects cells against the autocrine and paracrine effects of IL-1 at the signaling and transcriptional levels.

Adenoviridae↗
PubMed2003

Immunology and functional genomics of Behçet's disease.

Behçet's disease (BD) is a multisystemic inflammatory disorder. Although the cause and pathogenesis of BD are still unclear, there is evidence for genetic, immunologic and infectious factors at the onset or in the course of BD. This review focuses on the functional genomics and immunology of BD. HLA-B51 is the major disease susceptibility gene locus in BD. An increased number of gammadelta T cells in the peripheral blood and in the involved tissues have been reported. However, the T cells at the sites of inflammation appear to be a phenotypically distinct subset. There is also a significant gammadelta T cell proliferative response to mycobacterial 65-kDa heat shock protein peptides. Homologous peptides derived from the human 60-kDa heat shock protein were observed in BD patients. There is evidence that natural killer T cells may also play a role in BD.

Animals↗
PubMed2001

From chromosomal alterations to target genes for therapy: integrating cytogenetic and functional genomic views of the breast cancer genome.

A vast number of recurrent chromosomal alterations have been implicated in cancer development and progression. However, most of the genes involved in recurrent chromosomal alterations in solid tumors remain unknown, despite the recent substantial progress in genomic research and availability of high-throughput technologies. For example, it is now possible to quickly identify large numbers of differentially expressed genes in cancer specimens using cDNA microarrays. Integration of this "functional genomic view" of the cancer genome with the "cytogenetic view" could lead to the identification of genes playing a critical role in cancer development and progression. In this review, we illustrate how the combination of three different microarray technologies, cDNA, CGH, and tissue microarrays, makes it possible to directly identify genes involved in chromosomal rearrangements in cell line model systems and then rapidly explore their significance as potential diagnostic and therapeutic targets in human primary breast cancer progression.

Breast Neoplasms↗
PubMed1998

Microarrays: biotechnology's discovery platform for functional genomics.

Advances in microarray technology enable massive parallel mining of biological data, with biological chips providing hybridization-based expression monitoring, polymorphism detection and genotyping on a genomic scale. Microarrays containing sequences representative of all human genes may soon permit the expression analysis of the entire human genome in a single reaction. These 'genome chips' will provide unprecedented access to key areas of human health, including disease prognosis and diagnosis, drug discovery, toxicology, aging, and mental illness. Microarray technology is rapidly becoming a central platform for functional genomics.

Biotechnology↗
PubMed2006

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach.

We describe a comprehensive translational approach for identifying candidate genes for alcoholism. The approach relies on the cross-matching of animal model brain gene expression data with human genetic linkage data, as well as human tissue data and biological roles data, an approach termed convergent functional genomics. An analysis of three animal model paradigms, based on inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to treatments with alcohol, was used. A comprehensive analysis of microarray gene expression data from five key brain regions (frontal cortex, amygdala, caudate-putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like integration of multiple independent lines of evidence, each by itself lacking sufficient discriminatory power, led to the identification of high probability candidate genes, pathways and mechanisms for alcoholism. These data reveal that alcohol has pleiotropic effects on multiple systems, which may explain the diverse neuropsychiatric and medical pathology in alcoholism. Some of the pathways identified suggest avenues for pharmacotherapy of alcoholism with existing agents, such as angiotensin-converting enzyme (ACE) inhibitors. Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show a marked modulation of alcohol intake. Other pathways are new potential targets for drug development. The emergent overall picture is that physical and physiological robustness may permit alcohol-preferring individuals to withstand the aversive effects of alcohol. In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur.

Alcohol Drinking↗