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 1,441 records · Page 80Linked to original sources
PubMed2005

Computational identification of human mitochondrial proteins based on homology to yeast mitochondrially targeted proteins.

MOTIVATION: Patients with defects of the mitochondrial respiratory chain due to mutations in nuclear genes are often undiagnosable due to the lack of information about the role of these genes. We therefore sought to produce a novel dataset of human nuclear-encoded mitochondrial proteins. RESULTS: We have used the web-based computer program Mitoprot to predict which proteins in the Saccharomyces cerevisiae genome are targeted to mitochondria. We then used this protein dataset to identify the homologous human proteins in the Unigene database using TBLASTN from NCBI. Human proteins with an Expectation value <10(-5) and an Identity >30% were accepted as true homologues of the yeast proteins. These human proteins were then reanalyzed with Mitoprot. The final set of proteins comprises a dataset of 361 human mitochondrially targeted proteins with homology to all S.cerevisiae mitochondrially targeted proteins. One hundred twenty eight of these proteins are novel and are of unknown function. SUPPLEMENTARY INFORMATION: Supplementary tables will be available from http://www.sickkids.ca/Robinsonlab/

Conserved Sequence↗
PubMed2000

[Transcriptome analysis and pharmacogenomics].

Pharmacogenomics is defined as identification of loci which are involved in determining the responsiveness and distinguishing responders and non-responders to a given drug. Genome sequencing, transcriptome and proteome analysis are of particular significance in pharmacogenomics. Sequencing is used to locate polymorphisms, and monitoring of gene expression can provide clues about the genomic response to disease and treatment. The transcriptome analysis can be done by methods of random cDNA sequencing (expressed sequence tag project, body map project, serial analysis of gene expression, etc.), mRNA display (differential display, fluorescent differential display, RNA arbitrary primed PCR, molecular indexing, gene expression fingerprinting, etc.) and differential hybridization (cDNA high density filter, cDNA microarray, oligomicrochip, etc.). We describe the principle and application of trancriptome analysis in pharmacogenomics, especially differential display and cDNA microarray. We used transcriptome analysis to identify therapeutic target genes by studying the change of gene expression in animal models of oxidative stress and hypoxia and found novel drug target candidates through this pharmacogenomic strategy.

Animals↗
PubMed2005

Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling.

The yeast histone variant H2AZ (Htz1) is implicated in transcription activation, prevention of the ectopic spread of heterochromatin, and genome integrity. Our genome-wide localization analysis revealed that Htz1 is widely, but nonrandomly, distributed throughout the genome in an SWR1-dependent manner. We found that Htz1 is enriched in intergenic regions compared with coding regions. Its occupancy is inversely proportional to transcription rates and the enrichment of the RNA polymerase II under different growth conditions. However, Htz1 does not seem to directly regulate transcription repression genome-wide; instead, the presence of Htz1 under the inactivated condition is essential for optimal activation of a subset of genes. In addition, Htz1 is not generally responsible for nucleosome positioning, even at those promoters where Htz1 is highly enriched. Finally, using a biochemical approach, we demonstrate that incorporation of Htz1 into nucleosomes inhibits activities of histone modifiers associated with transcription, Dot1, Set2, and NuA4 and reduces the nucleosome mobilization driven by chromatin remodeling complexes. These lines of evidence collectively suggest that Htz1 may serve to mark quiescent promoters for proper activation.

Chromatin Assembly and Disassembly↗
PubMed2005

A microarray analysis of the rice transcriptome and its comparison to Arabidopsis.

Arabidopsis and rice are the only two model plants whose finished phase genome sequence has been completed. Here we report the construction of an oligomer microarray based on the presently known and predicted gene models in the rice genome. This microarray was used to analyze the transcriptional activity of the gene models in representative rice organ types. Expression of 86% of the 41,754 known and predicted gene models was detected. A significant fraction of these expressed gene models are organized into chromosomal regions, about 100 kb in length, that exhibit a coexpression pattern. Compared with similar genome-wide surveys of the Arabidopsis transcriptome, our results indicate that similar proportions of the two genomes are expressed in their corresponding organ types. A large percentage of the rice gene models that lack significant Arabidopsis homologs are expressed. Furthermore, the expression patterns of rice and Arabidopsis best-matched homologous genes in distinct functional groups indicate dramatic differences in their degree of conservation between the two species. Thus, this initial comparative analysis reveals some basic similarities and differences between the Arabidopsis and rice transcriptomes.

Arabidopsis↗
PubMed2005

Toward functional genomics of flow-induced outward remodeling of resistance arteries.

In resistance-sized arteries, a chronic increase in blood flow leads to increases in arterial structural luminal diameter and arterial wall mass. In this review, we summarize recent evidence that outward remodeling of resistance arteries 1) can help maintain and restore tissue perfusion, 2) is not intimately related to flow-induced vasodilatation, 3) involves transient dedifferentiation and turnover of arterial smooth muscle cells, and 4) is preceded by increased expression of matricellular proteins, which have been shown to promote disassembly of focal adhesion sites. Studies of experimental and physiological resistance artery remodeling involving differential gene expression analyses and the use of knockout and transgenic mouse models can help unravel the mechanisms of outward remodeling.

Animals↗
PubMed2005

Genomics-based prognosis and therapeutic prediction in breast cancer.

Breast cancer is a heterogeneous disease. DNA microarray technology is being applied to breast cancer to identify new prognostic biomarkers, to predict response to therapy, and to discover targets for the development of novel therapies. New diagnostic assays based on global gene expression are being introduced into clinical practice or tested in large-scale clinical trials. This review focuses on translational studies using microarray analyses and discusses best practice features and pitfalls. We note that factors that predict metastatic disease are not necessarily the same factors that predict therapeutic response. We believe that the characterization and discernment of different systems among breast cancers is crucial for understanding drug sensitivity and resistance mechanisms and for guiding therapy.

Antineoplastic Agents↗
PubMed2003

ESTMAP: a system for expressed sequence tags mapping on genomic sequences.

The completion of a number of large genome sequencing projects emphasizes the importance of protein-coding gene predictions. Most of the problems associated with gene prediction are caused by the complex exon-intron structures commonly found in eukaryotic genomes. However, information from homologous sequences can significantly improve the accuracy of the prediction. In particular, expressed sequence tags (ESTs) are very useful for this purpose, since currently existing EST collections are very large. We developed an ESTMAP system, which utilizes homology searches against a database of repetitive elements using the RepeatView program and the EST Division of GenBank using the BLASTN program. ESTMAP extracts "exact" matches with EST sequences (> 95% of homology) from BLASTN output file and predicts introns in DNA comparing ESTs and a query sequence. ESTMAP is implemented as a part of the WebGene system (http://www.cnr.it/webgene).

Base Sequence↗
PubMed2004

Making sense of molecular signatures in the immune system.

The development of Functional Genomics technologies has opened new avenues to investigate the complexity of the immune system. Microarray technology has been particularly successful because of its relatively low cost and high genome coverage. Consequently to our ability to monitor the expression of a significant proportion of an organism genome, our understanding of the molecular dynamics behind cell differentiation and cell response has greatly improved. Molecular signatures associated to immune cells have provided important tools to investigate the molecular basis of diseases and have been often associated to diagnostic and prognostic markers. The availability of such large collection of data has stimulated the application of complex machine learning techniques in the attempt to link molecular signatures and cell physiology. Here we review the most recent developments in the analysis of molecular signatures in the immune system.

Animals↗
PubMed2006

Deconstructing language by comparative gene expression: from neurobiology to microarray.

Language is a defining characteristic of our species that has emerged quite recently on an evolutionary timescale. Understanding the neurobiological substrates and genetic underpinnings of language constitutes a basic challenge for both neuroscience and genetics. The functional localization of language in the brain has been progressively refined over the last century through studies of aphasics and more recently through neuroimaging. Concurrently, structural specializations in these brain regions have been identified by virtue of their lateralization in humans and also through comparisons with homologous brain regions in non-human primate species. Comparative genomics has revealed the genome of our closest living relative, the chimpanzee, to be astonishingly similar to our own. To explore the role that changes in the regulation of gene expression have had in recent human evolution, several groups have used microarrays to compare expression levels for thousands of genes in the brain between humans and chimpanzees. By applying this approach to the increasingly refined peri-sylvian network of brain regions involved in language, it may be possible to discern functionally significant changes in gene expression that are universal among humans but unique to our species, thus casting light on the molecular basis of language in the brain.

Animals↗
PubMed2002

[Individuated molecular target chemotherapy].

Developing the technological innovation for genomic and molecular biology rapidly, the strategy of molecular target chemotherapy for cancer is recognized in the medical circles to be defined on the basic science and the ethical society. The novel strategy of the individuated anticancer chemotherapy is growing of geno-projects to be determined of more effective and harmless therapeutic methods for every cancer patients by the individual difference of pharmacogenetics and molecular biology. The new strategy is dependent on the general analysis for the personal life science from pharmacokinetics, pharmacodynamics, and oncogenomics. We summarized the problems and the possibility of the translational research for these strategies from the position of medical oncology.

Antineoplastic Agents↗
PubMed2004

Parasite-specific immune response in adult Drosophila melanogaster: a genomic study.

Insects of the order Diptera are vectors for parasitic diseases such as malaria, sleeping sickness and leishmania. In the search for genes encoding proteins involved in the antiparasitic response, we have used the protozoan parasite Octosporea muscaedomesticae for oral infections of adult Drosophila melanogaster. To identify parasite-specific response molecules, other flies were exposed to virus, bacteria or fungi in parallel. Analysis of gene expression patterns after 24 h of microbial challenge, using Affymetrix oligonucleotide microarrays, revealed a high degree of microbe specificity. Many serine proteases, key intermediates in the induction of insect immune responses, were uniquely expressed following infection of the different organisms. Several lysozyme genes were induced in response to Octosporea infection, while in other treatments they were not induced or downregulated. This suggests that lysozymes are important in antiparasitic defence.

Animals↗
PubMed2004

From masking repeats to identifying functional repeats in the mouse transcriptome.

The back-to-back release of the mouse genome and the functionally annotated RIKEN mouse full-length cDNA collection was an important milestone in mammalian genomics. Yet much of the data remain to be explored in terms of biological effects and mechanisms. For example, interspersed repeats account for 39 per cent of the mouse genome sequence and 11 per cent of representative transcripts. A considerable number of transposable repeat elements are still active and propagating in mouse compared with human. While existing repeat databases and tools assist the classification of repeats or identification of new repeats, there is little bioinformatic support towards exploring the extent and role of repeats in transcriptional variation, modulation of protein function, or gene regulatory events. Since the mouse is used as a model organism to study human genes and their disease associations, this review focuses on information extraction and collation that captures the functional context of repeats in mouse transcripts to facilitate the biological interpretation and extrapolation of findings to the human.

Animals↗
PubMed2005

Tools enabling the elucidation of molecular pathways active in human disease: application to Hepatitis C virus infection.

BACKGROUND: The extraction of biological knowledge from genome-scale data sets requires its analysis in the context of additional biological information. The importance of integrating experimental data sets with molecular interaction networks has been recognized and applied to the study of model organisms, but its systematic application to the study of human disease has lagged behind due to the lack of tools for performing such integration. RESULTS: We have developed techniques and software tools for simplifying and streamlining the process of integration of diverse experimental data types in molecular networks, as well as for the analysis of these networks. We applied these techniques to extract, from genomic expression data from Hepatitis C virus-infected liver tissue, potentially useful hypotheses related to the onset of this disease. Our integration of the expression data with large-scale molecular interaction networks and subsequent analyses identified molecular pathways that appear to be induced or repressed in the response to Hepatitis C viral infection. CONCLUSION: The methods and tools we have implemented allow for the efficient dynamic integration and analysis of diverse data in a major human disease system. This integrated data set in turn enabled simple analyses to yield hypotheses related to the response to Hepatitis C viral infection.

Computational Biology↗
PubMed2006

A classification based framework for quantitative description of large-scale microarray data.

Genome-wide surveys of transcription depend on gene classifications for the purpose of data interpretation. We propose a new information-theoretical-based method to: assess significance of co-expression within any gene group; quantitatively describe condition-specific gene-class activity; and systematically evaluate conditions in terms of gene-class activity. We applied this technique to describe microarray data tracking Escherichia coli transcriptional responses to more than 30 chemical and physiological perturbations. We correlated the nature and breadth of the responses with the nature of perturbation, identified gene group proxies for the perturbation classes and quantitatively compared closely related physiological conditions.

Cell Proliferation↗
PubMed2004

Bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers.

The DNA microarray has revolutionized cancer research. Now, scientists can obtain a genome-wide perspective of cancer gene expression. One potential application of this technology is the discovery of novel cancer biomarkers for more accurate diagnosis and prognosis, and potentially for the earlier detection of disease or the monitoring of treatment effectiveness. Because microarray experiments generate a tremendous amount of data and because the number of laboratories generating microarray data is rapidly growing, new bioinformatics strategies that promote the maximum utilization of such data are necessary. Here, we describe a method to validate multiple microarray data sets, a Web-based cancer microarray database for biomarker discovery, and methods for integrating gene ontology annotations with microarray data to improve candidate biomarker selection.

Biomarkers, Tumor↗
PubMed2004

Genome-wide analysis of STAT target genes: elucidating the mechanism of STAT-mediated oncogenesis.

Inappropriate activation of transcription factors is a common event in cancer. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. An important goal remains identifying the targets of oncogenic transcription factors that execute these changes. STAT proteins are among the best-studied of these transcription factors, and are involved in oncogenesis both in vivo and in vitro. They thus represent an ideal model for understanding how transcription factors cause cancer through coordinated changes in gene expression. Recent studies have employed microarray-based expression analysis to comprehensively identify STAT target genes. Analysis of these targets can provide insight into mechanisms of neoplastic transformation, and may shed light on new strategies for targeted therapy.

Animals↗
PubMed2006

Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells.

Stem cells have the remarkable ability to give rise to both self-renewing and differentiating daughter cells. Drosophila neural stem cells segregate cell-fate determinants from the self-renewing cell to the differentiating daughter at each division. Here, we show that one such determinant, the homeodomain transcription factor Prospero, regulates the choice between stem cell self-renewal and differentiation. We have identified the in vivo targets of Prospero throughout the entire genome. We show that Prospero represses genes required for self-renewal, such as stem cell fate genes and cell-cycle genes. Surprisingly, Prospero is also required to activate genes for terminal differentiation. We further show that in the absence of Prospero, differentiating daughters revert to a stem cell-like fate: they express markers of self-renewal, exhibit increased proliferation, and fail to differentiate. These results define a blueprint for the transition from stem cell self-renewal to terminal differentiation.

Animals↗
PubMed2005

A nutrigenomics database--integrated repository for publications and associated microarray data in nutrigenomics research.

In the current situation where microarray data in the field of nutritional genomics (nutrigenomics) are accumulating rapidly, there is imminent need for an efficient data infrastructure to support research workflow. We have established a web-based, integrated database of the publications and microarray expression data in the field of nutrigenomics. The registered data include links to external databases such as PubMed of the National Center for Biotechnology Information and public microarray databases that contain Minimum Information About a Microarray Experiment-compliant microarray expression data. Using this database, all data sets created will be effectively utilized and shared with other researchers. This database is built on an open-source database system and is freely accessible via the World Wide Web (http://a-yo5.ch.a.u-tokyo.ac.jp/index.phtml).

Databases, Genetic↗