Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genomic profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources

Ontology-driven approaches to analyzing data in functional genomics.

Ontologies are fundamental knowledge representations that provide not only standards for annotating and indexing biological information, but also the basis for implementing functional classification and interpretation models. This chapter discusses the application of gene ontology (GO) for predictive tasks in functional genomics. It focuses on the problem of analyzing functional patterns associated with gene products. This chapter is divided into two main parts. The first part overviews GO and its applications for the development of functional classification models. The second part presents two methods for the characterization of genomic information using GO. It discusses methods for measuring functional similarity of gene products, and a tool for supporting gene expression clustering analysis and validation.

Cluster Analysis↗

Occurrence of Salmonella enterica serotype typhimurium DT104A in retail ground beef.

Surveillance data of cattle and human isolates of Salmonella enterica serovar Typhimurium DT104 indicate that this pathogen emerged worldwide in the 1980s, particularly in cattle. Studies were conducted to determine the prevalence of Salmonella Typhimurium DT104 in ground beef. Samples were also tested for the presence of generic Escherichia coli. A total of 404 fresh ground beef samples obtained at retail stores from New York, San Francisco, Philadelphia, Denver, Atlanta, Houston, and Chicago were shipped overnight to Georgia for processing. Salmonella spp. were isolated from 14 (3.5%) samples. Eight different serotypes were identified among the isolates, including Salmonella Typhimurium (5), Salmonella Lille (3), Salmonella Montevideo (1), Salmonella Hadar (1), Salmonella Meleagridis (1), Salmonella Cerro (1), Salmonella Kentucky (1), and Salmonella Muenster (1). Antibiotic resistance profiles indicated that all five Salmonella Typhimurium isolates were resistant to ampicillin, streptomycin, sulfamethoxazole, ticarcillin, and tetracycline but that they were sensitive to chloramphenicol. Phage typing revealed that all five Salmonella Typhimurium isolates were DT104A, a subtype of DT104. All five Salmonella Typhimurium DT104A isolates were obtained from ground beef sampled from retail outlets in San Francisco. Pulsed-field gel electrophoresis (PFGE) genomic DNA profiles of the five Salmonella Typhimurium DT104A isolates from ground beef were indistinguishable from those of four control Salmonella Typhimurium DT104 penta-resistant isolates from cattle that were used for comparison. A total of 102 generic E. coli isolates were obtained, only three of which were multiresistant to antibiotics. In addition, three E. coli isolates were recovered from samples that were positive for Salmonella Typhimurium DT104A. No correlation of antibiotic resistance profiles was observed between Salmonella Typhimurium DT104A and generic E. coli, as two of the three E. coli isolates were susceptible to all of the antibiotics tested, and the third isolate was resistant only to cephalothin. These data indicate that Salmonella Typhimurium DT104A can be isolated from retail ground beef, and because there was little overlap in antibiotic resistance patterns between Salmonella Typhimurium DT104A and E. coli isolates from the same ground beef samples, these limited data suggest that the transfer of antibiotic resistance genes among enteric bacteria in ground beef may not be common. This latter observation is further supported by the limited isolation of multiantibiotic-resistant E. coli from retail ground beef.

Animals↗

Identification of G protein-coupled receptor genes from the human genome sequence.

We have identified novel G protein-coupled receptors (GPCRs) with no introns in the coding region from the human genome sequence: 322 olfactory receptors; 22 taste receptors; 128 registered GPCRs for endogenous ligands; 50 novel GPCR candidates homologous to registered GPCRs for endogenous ligands; and 59 novel GPCR candidates not homologous to registered GPCRs. The total number of GPCRs with and without introns in the human genome was estimated to be approximately 950, of which 500 are odorant or taste receptors and 450 are receptors for endogenous ligands.

Adult↗

A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans.

Transposon jumps are a major cause of genome instability. In the C. elegans strain Bristol N2, transposons are active in somatic cells, but they are silenced in the germline, presumably to protect the germline from mutations. Interestingly, the transposon-silencing mechanism shares factors with the RNAi machinery. To better understand the mechanism of transposon silencing, we performed a genome-wide RNAi screen for genes that, when silenced, cause transposition of Tc1 in the C. elegans germline. We identified 27 such genes, among which are mut-16, a mutator that was previously found but not identified at the molecular level, ppw-2, a member of the argonaute family, and several factors that indicate a role for chromatin structure in the regulation of transposition. Some of the newly identified genes are also required for cosuppression and therefore represent the shared components of the two pathways. Since most of the newly identified genes have clear homologs in other species, and since transposons are found from protozoa to human, it seems likely that they also protect other genomes against transposon activity in the germline.

Animals↗

A comparative phylogenetic approach for dating whole genome duplication events.

MOTIVATION: Whole genome duplications have played a major role in determining the structure of eukaryotic genomes. Current evidence revealing large blocks of duplicated chromatin yields new insights into the evolutionary history of species, but also presents a major challenge for researchers attempting to utilize comparative genomics techniques. Understanding the timing of duplication events relative to divergence among taxa is critical to accurate and comprehensive cross-species comparisons. RESULTS: We describe a large-scale approach to estimate the timing of duplication events in a phylogenetic context. The methodology has been previously utilized for analysis of Arabidopsis and Saccharomyces duplication events. This new implementation provides a more flexible and reusable framework for these analyses. Scripts written in the Python programming language drive a number of freely available bioinformatics programs, creating a no-cost tool for researchers. The usefulness of the approach is demonstrated through genome-scale analysis of Arabidopsis and Oryza (rice) duplications. AVAILABILITY: Software and documentation are freely available from http://plantgenome.agtec.uga.edu/bioinformatics/dating/

Algorithms↗

Use of genomics tools to isolate key ripening genes and analyse fruit maturation in tomato.

Development, maturation and ripening of fruits has received considerable experimental attention, primarily due to the uniqueness of such processes to plant species and the importance of fruit as a significant aspect of human dietary intake and nutrition. Molecular and genetic analysis of fruit development, and especially ripening of fleshy fruits, has resulted in significant gains in knowledge over recent years, especially with respect to understanding ethylene biosynthesis and response, cell wall metabolism and, to a lesser extent, environmental cues which impact ripening. Tomato has proved to be an excellent model system for the analysis of fruit ripening and development, in part due to the availability of well characterized ripening mutants. Especially interesting are the non-allelic ripening-inhibitor (rin) and non-ripening (nor) mutations which result in non-ripening fruit. Fruit from both mutants are deficient in climacteric respiration and the associated burst in ethylene biosynthesis. Exogenous ethylene does not restore ripening yet does induce expression of ethylene-regulated ripening genes, suggesting both mutations block necessary aspects of ripening outside the realm of ethylene's influence. Both mutations therefore represent genes upstream of ethylene control and additional non-ethylene mediated aspects of ripening. Both genes have recently been isolated through positional cloning strategies and it was shown that ripening is regulated, in part, by a MADS-box transcription factor at the rin locus. Recent development of tools for tomato genomics summarized here have further expanded the potential of the tomato system for the elucidation of genetic regulatory components impacting fruit development, ripening and nutritional quality.

Cell Wall↗

Functional genomic analysis of herpes simplex virus type 1 counteraction of the host innate response.

Herpes simplex virus type 1 (HSV-1) mutants lacking the ICP34.5 gene are severely attenuated in mouse models and have a significant growth defect in confluent mouse embryo fibroblasts. Previously, ICP34.5 was demonstrated to have a crucial role in evading the innate immune response to infection by mediating the dephosphorylation of eIF2alpha, a translation initiation factor phosphorylated by PKR during the antiviral response. To further understand the role of ICP34.5 in evasion of the antiviral response, we used transcriptional profiling to examine host cell gene expression in both wild-type and ICP34.5-null virus-infected mouse embryo fibroblasts over a time course of infection. Our study revealed that cells responded to infection within 3 h through PKR-dependent eIF2alpha phosphorylation and that the majority of up-regulated genes at 3 h postinfection were involved in the antiviral response. HSV-1 counters this response through early expression of ICP34.5 and dephosphorylation of eIF2alpha. By 12 h postinfection, the differences between the number and functional classification of genes differentially up- and down-regulated between wild-type and ICP34.5-null virus-infected cells were maximal. Specifically, in wild-type virus-infected cells, the majority of changed genes were involved in metabolic and biosynthetic processes, while in ICP34.5-null virus-infected cells, mostly antiviral genes were up-regulated. Further, ICP34.5-null virus-infected cells produced greater amounts of beta interferon than wild-type virus-infected cells. These results indicate that ICP34.5 expression and function at early times postinfection have a pivotal role in the ability of HSV-1 to gain control of the host cell and maintain an environment for successful viral replication.

Animals↗

Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis.

The molecular mechanisms that regulate asymmetric divisions of hematopoietic progenitor cells (HPCs) are not yet understood. The slow-dividing fraction (SDF) of HPCs is associated with primitive function and self-renewal, whereas the fast-dividing fraction (FDF) predominantly proceeds to differentiation. CD34+/CD38- cells of human umbilical cord blood were separated into the SDF and FDF. Genomewide gene expression analysis of these populations was determined using the newly developed Human Transcriptome Microarray containing 51 145 cDNA clones of the Unigene Set-RZPD3. In addition, gene expression profiles of CD34+/CD38- cells were compared with those of CD34+/CD38+ cells. Among the genes showing the highest expression levels in the SDF were the following: CD133, ERG, cyclin G2, MDR1, osteopontin, CLQR1, IFI16, JAK3, FZD6, and HOXA9, a pattern compatible with their primitive function and self-renewal capacity. Furthermore, morphologic differences between the SDF and FDF were determined. Cells in the SDF have more membrane protrusions and CD133 is located on these lamellipodia. The majority of cells in the SDF are rhodamine-123dull. These results provide molecular evidence that the SDF is associated with primitive function and serves as basis for a detailed understanding of asymmetric division of stem cells.

ADP-ribosyl Cyclase↗

Global protein function annotation through mining genome-scale data in yeast Saccharomyces cerevisiae.

As we are moving into the post genome-sequencing era, various high-throughput experimental techniques have been developed to characterize biological systems on the genomic scale. Discovering new biological knowledge from the high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed a Bayesian statistical method together with Boltzmann machine and simulated annealing for protein functional annotation in the yeast Saccharomyces cerevisiae through integrating various high-throughput biological data, including yeast two-hybrid data, protein complexes and microarray gene expression profiles. In our approach, we quantified the relationship between functional similarity and high-throughput data, and coded the relationship into 'functional linkage graph', where each node represents one protein and the weight of each edge is characterized by the Bayesian probability of function similarity between two proteins. We also integrated the evolution information and protein subcellular localization information into the prediction. Based on our method, 1802 out of 2280 unannotated proteins in yeast were assigned functions systematically.

Bayes Theorem↗

A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors.

Krüppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets.

Computational Biology↗

Genome-Wide Analysis of DtxR and HrrA Regulons Reveals Novel Targets and a High Level of Interconnectivity Between Iron and Heme Regulatory Networks in Corynebacterium glutamicum.

Iron is vital for most organisms, serving as a cofactor in enzymes, regulatory proteins, and respiratory cytochromes. In Corynebacterium glutamicum , iron and heme homeostasis are tightly interconnected and controlled by the global regulators DtxR and HrrA. While DtxR senses intracellular Fe2+, HrrSA is activated by heme. This study provides the first genome-wide analysis of DtxR and HrrA binding dynamics under varying iron and heme conditions using chromatin affinity purification and sequencing (ChAP-Seq). We revealed 25 novel DtxR targets and 210 previously unrecognized HrrA targets. Among these, metH, encoding homocysteine methyltransferase, and xerC, encoding a tyrosine recombinase, were bound by DtxR exclusively under heme conditions, underscoring condition-dependent variation. Activation of metH by DtxR links iron metabolism to methionine synthesis, potentially relevant for the mitigation of oxidative stress. Beyond novel targets, 16 shared targets between DtxR and HrrA, some with overlapping operator sequences, highlight their interconnected regulons. Strikingly, we demonstrate the significance of weak ChAP-Seq peaks that are often disregarded in global approaches, but feature an impact of the regulator on differential gene expression. These findings emphasize the importance of genome-wide profiling under different conditions to uncover novel targets and shed light on the complexity and dynamic nature of bacterial regulatory networks.

Corynebacterium glutamicum↗

Extraction of phylogenetic network modules from prokayrote metabolic pathways.

In the post-genomic era, it is important to analyze interaction networks that include genes, proteins, enzymes and compounds such as a metabolic pathway. Every organism has such networks individually. However, several parts of them are conserved in different organisms. The purpose of this analysis is to extract sub-networks composed of these common elements through the phylogenetic analysis. We extracted network modules from metabolic pathways using phylogenetic profile and cluster analysis. The enzymes of these modules are related by evolutionary and functional correlation. Our results give a valuable insight into the evolution of metabolic pathways.

Bacteria↗

Global Profiling and Analysis of 5' Monophosphorylated mRNA Decay Intermediates.

During RNA turnover, the action of endo- and exo-ribonucleases can yield RNA decay intermediates with specific 5' ends. These RNA decay intermediates have been demonstrated to be the outcome of decapping, microRNA-directed endo-cleavage, or the protected fragments of ribosomes and exon-junction complexes. Therefore, global analysis of RNA decay intermediates can facilitate studies of many RNA decay pathways. In this chapter, we describe a high-throughput sequencing protocol named parallel analysis of RNA ends (PARE), which allows genome-wide profiling of 5' monophosphorylated mRNA decay intermediates from plants or other eukaryotes. Also, we present the tools and scripts necessary for the proper analysis of RNA degradome data obtained from the PARE method. Details and modifications of library construction procedures and bioinformatic analyses to optimize sequencing quality and cope with emerging sequencing platforms and findings are highlighted.

RNA Stability↗

Genomics of host-pathogen interactions.

The complete sequences of hundreds of microbial genomes have provided drug discovery pipelines with thousands of new potential drug targets. Their availability has also stimulated the development of a variety of innovative approaches that allow functional studies to be performed on the entire genome of an organism. This chapter describes how these approaches have been applied to the analysis of host-pathogen interactions and discusses how such studies might facilitate the development of new antibiotics.

Anti-Bacterial Agents↗

Plasmodium research in the postgenomic era.

The complete genomic sequence of Plasmodium falciparum strain 3D7 was published in October 2002. At the Next Steps in Malaria Research meeting in April 2005, the next practical steps were considered and the priorities ranked for postgenomic research in Plasmodium. The high-throughput approaches that will help to answer the major biological questions regarding Plasmodium should, like the genome project itself, build community-shared resources, and efforts must be made to help researchers ready themselves to use the tools that will become available.

Animals↗

The genomic revolution: what does it mean for human and ecological risk assessment?

The first sequencing of a complete organism genome occurred in 1995. Since then there has been an explosion of information, with a new organism being sequenced nearly every week. This rapid development of genomics is providing unparalleled opportunities in toxicology, ecology, and risk assessment. This paper provides an overview of some possible applications of this new information in ecological and human risk assessment.

Animals↗

DNA amplification method tolerant to sample degradation.

Despite recent advances in linear whole genome amplification of intact DNA/RNA, amplification of degraded nucleic acids in an unbiased fashion remains a serious challenge for genetic diagnosis. We describe a new whole genome amplification procedure, RCA-RCA (Restriction and Circularization-Aided Rolling Circle Amplification), which retains the allelic differences among degraded amplified genomes while achieving almost complete genome coverage. RCA-RCA utilizes restriction digestion and whole genome circularization to generate genomic sequences amenable to rolling circle amplification. When intact genomic DNA is used, RCA-RCA retains gene-amplification differences (twofold or higher) between complex genomes on a genome-wide scale providing highly improved concordance with unamplified material as compared with other amplification methodologies including multiple displacement amplification. Using RCA-RCA, formalin-fixed samples of modest or substantial DNA degradation were successfully amplified and screened via array-CGH or Taqman PCR that displayed retention of the principal gene amplification features of the original material. Microsatellite analysis revealed that RCA-RCA amplified genomic DNA is representative of the original material at the nucleotide level. Amplification of cDNA is successfully performed via RCA-RCA and results to unbiased gene expression analysis (R(2) = 0.99). The simplicity and universal applicability of RCA-RCA make it a powerful new tool for genome analysis with unique advantages over previous amplification technologies.

Cell Line, Tumor↗