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Results for “Genomic profiling”

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At least 1,711 records · Page 95Linked to original sources
PubMed2000

Preliminary profile of the Cryptosporidium parvum genome: an expressed sequence tag and genome survey sequence analysis.

Cryptosporidium parvum is a protozoan enteropathogen that infects humans and animals and causes a pronounced diarrheal disease that can be life-threatening in immunocompromised hosts. No specific chemo- or immunotherapies exist to treat cryptosporidiosis and little molecular information is available to guide development of such therapies. To accelerate gene discovery and identify genes encoding potential drug and vaccine targets we constructed sporozoite cDNA and genomic DNA sequencing libraries from the Iowa isolate of C. parvum and determined approximately 2000 sequence tags by single-pass sequencing of random clones. Together, the 567 expressed sequence tags (ESTs) and 1507 genome survey sequences (GSSs) totaled one megabase (1 mb) of unique genomic sequence indicating that approximately 10% of the 10.4 mb C. parvum genome has been sequence tagged in this gene discovery expedition. The tags were used to search the public nucleic acid and protein databases via BLAST analyses, and 180 ESTs (32%) and 277 GSSs (18%) exhibited similarity with database sequences at smallest sum probabilities P(N)< or =10(-8). Some tags encoded proteins with clear therapeutic potential including S-adenosylhomocysteine hydrolase, histone deacetylase, polyketide/fatty-acid synthases, various cyclophilins, thrombospondin-related cysteine-rich protein and ATP-binding-cassette transporters. Several anonymous ESTs encoded proteins predicted to contain signal peptides or multiple transmembrane spanning segments suggesting they were destined for membrane-bound compartments, the cell surface or extracellular secretion. One-hundred four simple sequence repeats were identified within the nonredundant sequence tag collection with (TAA)(> or =6)/(TTA)(> or =6) and (TA)(> or = 10)/(AT)(> or =10 ) being the most prevalent, occurring 40 and 15 times, respectively. Various cellular RNAs and their genes were also identified including the small and large ribosomal RNAs, five tRNAs, the U2 small nuclear RNA, and the small and large virus-like, double-stranded RNAs. This investigation has demonstrated that survey sequencing is an efficient procedure for gene discovery and genome characterization and has identified and sequence tagged many C. parvum genes encoding potential therapeutic targets.

Amino Acid Sequence↗
PubMed2002

Toxicogenomics and toxic torts.

One of the first practical applications of toxicogenomics will probably be in the context of toxic tort personal injury litigation. Gene expression changes that'fingerprint' exposure to particular classes of toxic substances can potentially be used to demonstrate exposure, prove causation and support novel damage claims in lawsuits brought by citizens injured by toxic exposures. Although the potential use of toxicogenomic data in toxic tort litigation is immense, there is a danger of premature use of such data before they have been adequately validated and characterized.

Causality↗
PubMed2001

A peptide profile of the Bacillus subtilis genome.

Bacillus subtilis is known to produce an abundance of small polypeptides. Several of these have antimicrobial activity and others are pheromones or extracellular factors that affect internal signal transduction systems. The completion of the B. subtilis genomic nucleotide sequence has revealed 345 small polypeptide open-reading frames (of 85 codons or less), 81% of which are of unknown function. A significant number of these reside in prophage genomes or phage-like elements where they can be organized into large operons. It is likely that many more exist in the genome of B. subtilis but are "hidden" entirely or partially within other reading frames, or possess non-conventional translation start signals and have escaped detection. The discovery of so many small polypeptide orfs (SPORFs) and the likelihood of many more pose a challenging problem for those undertaking the complete functional analysis of genes that constitute prokaryotic genomes. A survey of known and potential peptide-encoding reading frames is presented herein as an attempt to classify those that are found in the B. subtilis genome according to function inferred from homology searches and to conservation among products of other microbial genomes.

Amino Acid Sequence↗
PubMed2001

Gene expression microarrays: a 21st century tool for directed vaccine design.

DNA microarray technology is a new and powerful tool that allows the simultaneous analysis of a large number of nucleic acid hybridization experiments in a rapid and efficient fashion. The development of the DNA microarray chip has been driven by modern techniques of microelectronic fabrication, miniaturization and integration to produce what is referred to as "laboratory-on-chip" devices. The application of DNA chip technology includes the comprehensive analysis of multiple gene mutations and expressed sequences with regard to newer drug designs, host-pathogen interactions and the design of new vaccines. An advantage of microarray technology is that it can assist researchers to better define and understand the expression profile of a given genotype associated with disease, adverse effects from exposure to certain stimuli, or the ability to understand or predict immune responses to specific antigens. This paper briefly reviews DNA microarray technology and its implications with special reference to vaccine design. The technical aspects comprising array manufacturing and design, array hybridization, formatting, scanning and data handling are also briefly discussed.

Animals↗
PubMed2001

H-NS and H-NS-like proteins in Gram-negative bacteria and their multiple role in the regulation of bacterial metabolism.

In Escherichia coli, the H-NS protein plays an important role in the structure and the functioning of bacterial chromosome. A homologous protein has also been identified in several enteric bacteria and in closely related organisms such as Haemophilus influenzae. To get information on their structure and their function, we identified H-NS-like proteins in various microorganisms by different procedures. In silico analysis of their amino acid sequence and/or in vivo experiments provide evidence that more than 20 proteins belong to the same class of regulatory proteins. Moreover, large scale technologies demonstrate that, at least in E. coli, the loss of motility in hns mutants results from a lack of flagellin biosynthesis, due to the in vivo repression of flagellar gene expression. In contrast, several genes involved in adaptation to low pH are strongly induced in a H-NS deficient strain, resulting in an increased resistance to acidic stress. Finally, expression profiling and phenotypic analysis suggest that, unlike H-NS, its paralogous protein StpA does not play any role in these processes.

Amino Acid Sequence↗
PubMed2002

Toxicogenomics; transcript profiling and potential application to chemical allergy.

Novel transcript profiling technologies allow simultaneous measurement of the changes in expression of many hundreds or many thousands of genes. The availability of these methods has brought about revolutionary changes in many areas of investigative biology, where analyses of patterns of gene expression, rather than of individual genes, are being employed. The application of these technologies to toxicology (toxicogenomics) offers new opportunities for both mechanistic toxicity research and predictive toxicology. Here we provide an overview of the basic approaches used in this field. The development of a series of toxicology-specific microarrays in our own laboratory is discussed, together with an example of one area of mechanistic research, chemical allergy, where we believe judicious application of toxicogenomics will make an important contribution.

Animals↗
PubMed2002

Primary prevention: phytoprevention and chemoprevention of colorectal cancer.

Considering the various stages of carcinogenesis and the numerous tumor types and available chemoprevention agents, knowledge of the etiology and the type of cancer to be treated, or possibly prevented, and understanding of the mechanisms by which agents exert their chemoprevention benefits may provide for improved strategy in designing therapeutic regimens. Because cancer usually develops over a 10- to 20-year period, it may be necessary for some agents to be provided before or early in the initiation steps of carcinogenesis to have beneficial effects. On the other hand, some agents may be more suitable for CRC prevention if provided at a later stage of carcinogenesis. Gene array, genomics, and proteomics are useful tools in advancing our understanding of the molecular events involved in carcinogenesis and in identifying markers of risk and surrogate end-points for colorectal cancer progression. These techniques may also serve for screening, identifying, and providing treatment targets for high-risk patients populations. Treatment could be developed depending on a patient's individual needs and genomic tumor profile. Clinical markers and surrogate end-points should be considered, together with molecular measurements, to more accurately assess risk. NSAIDs and COXIBs are clinically recognized as chemoprevention agents, and clinical trials evaluating their efficacy are ongoing. Treatment protocols, including dose and timing, remain to be determined, however. DFMO may best be used in combination with other chemoprevention agents. Dietary fiber and calcium supplements, as part of an overall low-fat diet, may decrease CRC risk. Long-term compliance with this regimen may be necessary to effect a beneficial outcome. Folate holds promise but needs further investigation, especially because its beneficial effects may depend on cancer type. Phytochemicals have been identified as strong candidates for use as agents to prevent colorectal cancer in cell culture and in rodent models of carcinogenesis. Their potential as chemoprevention agents must be demonstrated in clinical trials. In vitro and animal studies indicated that combination therapy may be a promising strategy over the monotherapy approach; clinical trials addressing the safety and efficacy of some combinations (DFMO/sulindac, fiber/calcium) are underway. The gastrointestinal tract and other organs are constantly exposed to a mixture of potentially toxic compounds and molecules considered favorable to health. Homeostasis between stress-mediated by toxic compounds and defensive mechanisms, is key for the maintenance of health and the prevention of disease. Whereas aggressive pharmacologic treatment may be necessary for patients at high risk for cancer, dietary supplements may be useful for populations at normal risk. The message for cancer prevention in the general population may well remain: keep a balanced healthy diet, eating a variety from all food groups, as part of a healthy lifestyle that includes moderate exercise.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Are there biofilm-specific physiological pathways beyond a reasonable doubt?

The development of surface-attached communities called biofilms is often thought to be a regulated developmental process involving profound biofilm-specific modifications. Despite intense scrutiny and a growing body of evidence correlating changes in gene expression with the switch from planktonic-to-biofilm lifestyle, an integrated view of biofilm formation is still missing.

Biofilms↗
PubMed2002

Gene-expression profiling and the genetic dissection of complex disease.

Several recent studies have highlighted how combining the powerful techniques of microarray analysis and congenic-strain analysis may greatly facilitate unravelling the genetic basis of susceptibility to common autoimmune diseases. In addition to providing pointers to the genetic variants themselves, the pathway(s) they control may also be highlighted, thereby identifying new targets for therapeutic intervention.

Animals↗
PubMed2002

Predictive non-linear modeling of complex data by artificial neural networks.

An artificial neural network (ANN) is an artificial intelligence tool that identifies arbitrary nonlinear multiparametric discriminant functions directly from experimental data. The use of ANNs has gained increasing popularity for applications where a mechanistic description of the dependency between dependent and independent variables is either unknown or very complex. This machine learning technique can be roughly described as a universal algebraic function that will distinguish signal from noise directly from experimental data. The application of ANNs to complex relationships makes them highly attractive for the study of biological systems. Recent applications include the analysis of expression profiles and genomic and proteomic sequences.

Biochemical Phenomena↗
PubMedDate not supplied

Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins.

BACKGROUND: In all organisms, nutrients are primary regulators of signaling pathways that control transcription. In Saccharomyces cerevisiae, the Tor proteins regulate the transcription of genes sensitive to the quality of available nitrogen and carbon sources. Formation of a ternary complex of the immunosuppressant rapamycin, its immunophilin receptor Fpr1p and Tor1p or Tor2p results in the nuclear import of several nutrient- and stress-responsive transcription factors. RESULTS: We show that treating yeast cells with rapamycin results in a broader modulation of functionally related gene sets than previously understood. Using chemical epistasis and vector-based global expression analyses, we partition the transcriptional program induced by rapamycin among five effectors (TAP42, MKS1, URE2, GLN3, GAT1) of the Tor proteins, and identify how the quality of carbon and nitrogen sources impinge upon components of the program. Biochemical data measuring Ure2p phosphorylation coupled with the partition analysis indicate that there are distinct signaling branches downstream of the Tor proteins. CONCLUSIONS: Whole-genome transcription profiling reveals a striking similarity between shifting to low-quality carbon or nitrogen sources and treatment with rapamycin. These data suggest that the Tor proteins are central sensors of the quality of carbon and nitrogen sources. Depending on which nutrient is limited in quality, the Tor proteins can modulate a given pathway differentially. Integrating the partition analysis of the transcriptional program of rapamycin with the biochemical data, we propose a novel architecture of Tor protein signaling and of the nutrient-response network, including the identification of carbon discrimination and nitrogen discrimination pathways.

Carbon↗
PubMed2003

Identification of a new cryptochrome class. Structure, function, and evolution.

Cryptochrome flavoproteins, which share sequence homology with light-dependent DNA repair photolyases, function as photoreceptors in plants and circadian clock components in animals. Here, we coupled sequencing of an Arabidopsis cryptochrome gene with phylogenetic, structural, and functional analyses to identify a new cryptochrome class (cryptochrome DASH) in bacteria and plants, suggesting that cryptochromes evolved before the divergence of eukaryotes and prokaryotes. The cryptochrome crystallographic structure, reported here for Synechocystis cryptochrome DASH, reveals commonalities with photolyases in DNA binding and redox-dependent function, despite distinct active-site and interaction surface features. Whole genome transcriptional profiling together with experimental confirmation of DNA binding indicated that Synechocystis cryptochrome DASH functions as a transcriptional repressor.

Amino Acid Sequence↗