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 1,081 records · Page 60Linked to original sources
PubMed2005

Functional Genomics meets neurodegenerative disorders Part I: transcriptomic and proteomic technology.

Transcriptomics and proteomics are increasingly applied to gain a mechanistic insight into neurodegenerative disorders. These techniques not only identify distinct, differentially expressed mRNAs and proteins but are also employed to dissect signaling pathways and reveal networks by using an integrated approach. In part I of this back-to-back review, technical aspects are discussed: in the transcriptomics section, which includes enrichment by laser microcapture dissection, we comment on qRT-PCR, SAGE, subtractive hybridization, differential display and microarrays, including software packages. In the proteomics section we discuss two-dimensional (2D) gel electrophoresis, liquid chromatography, methods to label and enrich specific proteins or peptides, and different types of mass spectrometers. These tools have been applied to a range of neurodegenerative disorders and are discussed and integrated in part II (Functional Genomics meets neurodegenerative disorders. Part II: application and data integration).

Animals↗
PubMed2001

Genomic and funtional aspects of the rat MHC, the RT1 complex.

The major histocompatibility complex (MHC) plays a central role in controlling immune responsiveness, susceptibility to certain diseases and histo-incompatibility. A physical map of the complete rat MHC, the RTI complex, is presented based on a PAC clonal contig (RT1n haplotype). Expression profiling of various tissues of different inbred strains has been carried out for genes of the RT1-C/E/M region, and different types of variability of expression are shown. As an example of single gene analysis, the RT1-linked heat shock-inducible heat shock genes Hsp70-1 and Hsp70-2 have been studied. It is demonstrated that their gene products are able to increase lysability of target cells by cytotoxic T lymphocytes.

Animals↗
PubMed2006

Functional genomics of stress response in Pseudomonas putida KT2440.

The metabolically versatile soil bacterium Pseudomonas putida has to cope with numerous abiotic stresses in its habitats. The stress responses of P. putida KT2440 to 4 degrees C, pH 4.5, 0.8 M urea, and 45 mM sodium benzoate were analyzed by determining the global mRNA expression profiles and screening for stress-intolerant nonauxotrophic Tn5 transposon mutants. In 392 regulated genes or operons, 36 gene regions were differentially expressed by more than 2.5-fold, and 32 genes in 23 operons were found to be indispensable for growth during exposure to one of the abiotic stresses. The transcriptomes of the responses to urea, benzoate, and 4 degrees C correlated positively with each other but negatively with the transcriptome of the mineral acid response. The CbrAB sensor kinase, the cysteine synthase CysM, PcnB and VacB, which control mRNA stability, and BipA, which exerts transcript-specific translational control, were essential to cope with cold stress. The cyo operon was required to cope with acid stress. A functional PhoP, PtsP, RelA/SpoT modulon, and adhesion protein LapA were necessary for growth in the presence of urea, and the outer membrane proteins OmlA and FepA and the phosphate transporter PstBACS were indispensable for growth in the presence of benzoate. A lipid A acyltransferase (PP0063) was a mandatory component of the stress responses to cold, mineral acid, and benzoate. Adaptation of the membrane barrier, uptake of phosphate, maintenance of the intracellular pH and redox status, and translational control of metabolism are key mechanisms of the response of P. putida to abiotic stresses.

Bacterial Outer Membrane Proteins↗
PubMed2007

Biomarker discovery in epithelial ovarian cancer by genomic approaches.

Ovarian cancer is the fifth most common form of cancer in women in the United States. It is a complex disease composed of different histological grades and histological types. Most of epithelial ovarian cancer cases are detected at an advanced stage. Patients usually respond to primary treatment with surgery and chemotherapy. However, the disease usually recurs and is ultimately fatal. So far, a satisfactory screening procedure and regime to treat the recurrence disease are not available. High-throughput genomic analyses have the potential to change the detection and the treatment of ovarian neoplasms. They can help diagnose subtypes of disease and predict patient survival. New diagnostic and prognostic markers for ovarian cancer are emerging. One day, profiling may influence treatment decisions, informing both which patients should receive chemotherapy and what type of chemotherapeutic agents should be employed. As greater numbers of tumor samples are analyzed, the power of these profiling studies will increase, raising the possibility that novel molecular targets and less toxic therapies will be identified. These powerful techniques hold the potential to unravel the genetic origins of ovarian cancer. Hopefully, this will translate into earlier diagnosis and better patient outcome from disease.

Animals↗
PubMed2002

Integration of genomic datasets to predict protein complexes in yeast.

The ultimate goal of functional genomics is to define the function of all the genes in the genome of an organism. A large body of information of the biological roles of genes has been accumulated and aggregated in the past decades of research, both from traditional experiments detailing the role of individual genes and proteins, and from newer experimental strategies that aim to characterize gene function on a genomic scale. It is clear that the goal of functional genomics can only be achieved by integrating information and data sources from the variety of these different experiments. Integration of different data is thus an important challenge for bioinformatics. The integration of different data sources often helps to uncover non-obvious relationships between genes, but there are also two further benefits. First, it is likely that whenever information from multiple independent sources agrees, it should be more valid and reliable. Secondly, by looking at the union of multiple sources, one can cover larger parts of the genome. This is obvious for integrating results from multiple single gene or protein experiments, but also necessary for many of the results from genome-wide experiments since they are often confined to certain (although sizable) subsets of the genome. In this paper, we explore an example of such a data integration procedure. We focus on the prediction of membership in protein complexes for individual genes. For this, we recruit six different data sources that include expression profiles, interaction data, essentiality and localization information. Each of these data sources individually contains some weakly predictive information with respect to protein complexes, but we show how this prediction can be improved by combining all of them. Supplementary information is available at http:// bioinfo.mbb.yale.edu/integrate/interactions/.

Cell Cycle↗
PubMed2004

The visual language of synteny.

The study of polygenic disorders such as cardiovascular and metabolic diseases requires access to vast amounts of experimental and in silico data. Where animal models of disease are being used, visualization of syntenic genome regions is one of the most important tools supporting data analysis. We define what is required to visualize synteny in terms of the data being displayed, the screen layout, and user interaction. We then describe a prototype visualization tool, SyntenyVista, which provides integrated access to quantitative trait loci, microarray, and gene datasets. We believe that SyntenyVista is a significant step towards an improved representation of comparative genomics data.

Algorithms↗
PubMed2003

PCR-assisted contig extension: stepwise strategy for bacterial genome closure.

Finishing is rate limiting for genome projects, and improvements in the efficiency of complete genome-sequence compilation will require improved protocols for gap closure. Here we report a novel approach for extending shotgun contigs and closing gaps that we termed PCR-assisted contig extension (PACE). PACE depends on the capture of rare mismatched interactions that occur between arbitrary primers and template DNA of unknown sequence, even under highly stringent conditions, by means of elevated PCR-cycle repetition and the use of specific anchoring primers corresponding to adjacent regions of known sequence. Using PACE, we have generated extensions with an average of 1 kb from all contigs generated from the shotgun sequencing of a 5-Mb genome, which closed the majority of gaps with a single round of experimentation. This included the generation of multiple extensions for contigs that terminated in one of the eight copies of the rRNA operon. We calculate that the switch from shotgun sequencing to PACE should occur between 5- and 8-fold genome coverage for maximum benefit and minimum overall cost. PACE is a robust and straightforward strategy that should simplify the finishing phase of bacterial genome projects.

Chromobacterium↗
PubMed2004

Genomic and proteomic analysis of thirty-nine structural proteins of shrimp white spot syndrome virus.

White spot syndrome virus (WSSV) virions were purified from the hemolymph of experimentally infected crayfish Procambarus clarkii, and their proteins were separated by 8 to 18% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to give a protein profile. The visible bands were then excised from the gel, and following trypsin digestion of the reduced and alkylated WSSV proteins in the bands, the peptide sequence of each fragment was determined by liquid chromatography-nano-electrospray ionization tandem mass spectrometry (LC-nanoESI-MS/MS) using a quadrupole/time-of-flight mass spectrometer. Comparison of the resulting peptide sequence data against the nonredundant database at the National Center for Biotechnology Information identified 33 WSSV structural genes, 20 of which are reported here for the first time. Since there were six other known WSSV structural proteins that could not be identified from the SDS-PAGE bands, there must therefore be a total of at least 39 (33 + 6) WSSV structural protein genes. Only 61.5% of the WSSV structural genes have a polyadenylation signal, and preliminary analysis by 3' rapid amplification of cDNA ends suggested that some structural protein genes produced mRNA without a poly(A) tail. Microarray analysis showed that gene expression started at 2, 6, 8, 12, 18, 24, and 36 hpi for 7, 1, 4, 12, 9, 5, and 1 of the genes, respectively. Based on similarities in their time course expression patterns, a clustering algorithm was used to group the WSSV structural genes into four clusters. Genes that putatively had common or similar roles in the viral infection cycle tended to appear in the same cluster.

Amino Acid Sequence↗
PubMed2005

An overview of lung cancer genomics and proteomics.

Lung cancer is the cause of nearly 170,000 cancer deaths in the United States each year, accounting for nearly 25% of all deaths from cancer. The 5-yr survival rate for lung cancer is < 15% from the time of diagnosis. This is largely due to the late stage of diagnosis and the lack of effective treatments, reflecting the need for a better understanding of the mechanisms that underlie lung carcinogenesis. Unlike the study of a single gene, protein, or pathway, genomic and proteomic technologies enable a systematic overview that provides the potential to improve our understanding of this disease. Ultimately, this could improve the diagnosis, prognosis, and clinical management of patients with lung cancer. Here, we review studies that generated profiles of gene and protein expression in lung cancer specimens and relevant model systems, and make recommendations to facilitate the clinical application of these technologies.

Animals↗
PubMed2006

'Oming in on schistosomes: prospects and limitations for post-genomics.

The recent release of version 3 of the Schistosoma mansoni genome assembly has made a wealth of information available to researchers. Here, progress made in schistosome genomics and post-genomics is considered. The current status of knowledge about the genome, transcriptome, proteome, glycome and immunome is summarized and recent publications briefly reviewed. The prospects for advances in understanding schistosome biology are highlighted. Most importantly, the limitations (which are mostly technical) that need to be addressed before the full potential of the genome database(s) can be realized are emphasized.

Animals↗
PubMed2006

ForestTreeDB: a database dedicated to the mining of tree transcriptomes.

ForestTreeDB is intended as a resource that centralizes large-scale expressed sequence tag (EST) sequencing results from several tree species (http://foresttree.org/ftdb). It currently encompasses 344,878 quality sequences from 68 libraries, from diverse organs of conifer and hybrid poplar trees. It utilizes the Nimbus data model to provide a hosting system for multiple projects, and uses object-relational mapping APIs in Java and Perl for data accesses within an Oracle database designed to be scalable, maintainable and extendable. Transcriptome builds or unigene sets occupy the focal point of the system. Several of the five current species-specific unigenes were used to design microarrays and SNP resources. The ForestTreeDB web application provides the means for multiple combination database queries. It presents the user with a list of discrete queries to retrieve and download large EST datasets or sequences from precompiled unigene assemblies. Functional annotation assignment is not trivial in conifers which are distantly related to angiosperm model plants. Optimal annotations are achieved through database queries that integrate results from several procedures based open-source tools. ForestTreeDB aims to facilitate sequence mining of coherent annotations in multiple species to support comparative genomic approaches. We plan to continuously enrich ForestTreeDB with other resources through collaborations with other genomic projects.

Databases, Nucleic Acid↗
PubMed2001

Flexible use of high-density oligonucleotide arrays for single-nucleotide polymorphism discovery and validation.

A method for identifying and validating single nucleotide polymorphisms (SNPs) with high-density oligonucleotide arrays without the need for locus-specific polymerase chain reactions (PCR) is described in this report. Genomic DNAs were divided into subsets with complexity of ~10 Mb by restriction enzyme digestion and gel-based fragment size resolution, ligated to a common adaptor, and amplified with one primer in a single PCR reaction. As a demonstration of this approach, a total of 124 SNPs were located in 190 kb of genomic sequences distributed across the entire human genome by hybridizing to high-density variant detection arrays (VDA). A set of independent validation experiments was conducted for these SNPs employing bead-based affinity selection followed by hybridization of the affinity-selected SNP-containing fragments to the same VDA that was used to identify the SNPs. A total of 98.7% (74/75) of these SNPs were confirmed using both DNA dideoxynucleotide sequencing and the VDA methodologies. With flexible sample preparation, high-density oligonucleotide arrays can be tailored for even larger scale genome-wide SNP discovery as well as validation.

Cell Line↗
PubMed2006

Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns.

Comparative genomic studies have been useful in identifying transcriptional regulatory elements in higher eukaryotic genomes, but many important regulatory elements cannot be detected by such analyses due to evolutionary variations and alignment tool limitations. Therefore, in this study we exploit the highly conserved nature of epigenetic modifications to identify potential transcriptional enhancers. By using a high-resolution genome-wide mapping technique, which combines the chromatin immunoprecipitation and serial analysis of gene expression assays, we have recently determined the distribution of lysine 9/14-diacetylated histone H3 in human T cells. We showed the existence of 46,813 regions with clusters of histone acetylation, termed histone acetylation islands, some of which correspond to known transcriptional regulatory elements. In the present study, we find that 4679 sequences conserved between human and pufferfish coincide with histone acetylation islands, and random sampling shows that 33% (13/39) of these can function as transcriptional enhancers in human Jurkat T cells. In addition, by comparing the human histone acetylation island sequences with mouse genome sequences, we find that despite the conservation of many of these regions between these species, 21,855 of these sequences are not conserved. Furthermore, we demonstrate that about 50% (26/51) of these nonconserved sequences have enhancer activity in Jurkat cells, and that many of the orthologous mouse sequences also have enhancer activity in addition to conserved epigenetic modification patterns in mouse T-cell chromatin. Therefore, by combining epigenetic modification and sequence data, we have established a novel genome-wide method for identifying regulatory elements not discernable by comparative genomics alone.

Acetylation↗
PubMed2001

Acid-induced gene expression in Helicobacter pylori: study in genomic scale by microarray.

To understand the RNA expression in response to acid stress of Helicobacter pylori in genomic scale, a microarray membrane containing 1,534 open reading frames (ORFs) from strain 26695 was used. Total RNAs of H. pylori under growth conditions of pH 7.2 and 5.5 were extracted, reverse transcribed into cDNA, and labeled with biotin. Each microarray membrane was hybridized with cDNA probe from the same strain under two different pH conditions and developed by a catalyzed reporter deposition method. Gene expression of all ORFs was measured by densitometry. Among the 1,534 ORFs, 53 ORFs were highly expressed (> or = 30% of rRNA control in densitometry ratios). There were 445 ORFs which were stably expressed (<30% of rRNA in densitometry) under both pH conditions without significant variation. A total of 80 ORFs had significantly increased expression levels at low pH, while expressions of 4 ORFs were suppressed under acidic condition. The remaining 952 ORFs were not detectable under either pH condition. These data were highly reproducible and comparable to those obtained by the RNA slot blot method. Our results suggest that microarray can be used in monitoring prokaryotic gene expression in genomic scale.

Acids↗
PubMed2007

Genomewide expression profiles of rat model renal isografts from brain dead donors.

BACKGROUND: It has been well documented that two factors, brain death (BD) and ischemia/reperfusion (I/R) injury, have distinct but overlapping adverse influences on the clinical outcome of renal transplantation. METHOD: We previously established a rat model of renal isografting from brain dead donors. In the present study, we performed genomic expression profiling with a high-density oligonucleotide microarray to identify genes that were upregulated or downregulated by BD and/or I/R injury. RESULTS: Among a total of 20,550 genes, most of those upregulated by BD were genes for adhesion molecules and cytokines or for chemokines such as Gro1 and IP-10. When overexpression of these genes was assessed by real-time reverse transcriptase-polymerase chain reaction, it was only observed one hr after the engraftment of kidneys from BD donors and returned to baseline thereafter, indicating the presence of an acute systemic inflammatory response to BD. Analysis of biologic networks demonstrated the activation of specific pathways that were clearly different for BD and I/R injury. The p53 and NFkappaB pathway was involved in the acute response to BD, whereas the Myc, Jun, and c-fos pathway was involved in I/R injury. Investigation of secretory protein genes identified LCN2 and SPP1 as candidate genes for biologic markers. CONCLUSION: Because our experimental system is a good model of renal transplantation from brain dead or living human donors, our data may be useful for elucidating the pathologic processes involved and for identification of novel markers for graft dysfunction of renal transplantation.

Animals↗
PubMed2026

Genome-wide identification and expression profiling of CSP and OBP genes in Stictocephala bisonia reveals candidate genes potentially associated with insecticide response.

Stictocephala bisonia is an important invasive agricultural pest. Due to the frequent application of insecticides in its habitat, this species is under intense selection pressure. Chemosensory proteins (CSPs) and odorant-binding proteins (OBPs) are known to play key roles in insecticide resistance, but their specific functions in S. bisonia remain unclear. In this study, we identified a total of 22 SbisCSPs and 16 SbisOBPs based on the S. bisonia genome. To screen for candidate genes potentially linked to insecticide resistance, we adopted a multi-criteria screening strategy that integrated phylogenetic analysis, molecular docking with three insecticides, and tissue-specific expression profiling. Phylogenetic analysis identified several SbisCSPs and SbisOBPs clustering with genes known to be involved in insecticide resistance, serving as an initial evolutionary filter. Molecular docking results indicated that &#x3bb;-Cyhalothrin exhibited the strong predicted binding affinity with most of SbisCSPs and SbisOBPs. Subsequent qPCR validation of seven prioritized candidates revealed distinct expression patterns: SbisCSP22 was highly expressed in adults and demonstrated strong binding affinity to all three insecticides tested, suggesting a potential role in mediating multi-insecticide response. Conversely, SbisCSP17 was significantly upregulated in larvae, clustered with genes known to mediate imidacloprid resistance, and exhibited strong binding affinity to imidacloprid. Given its larval-specific expression and the soil-dwelling behavior of larvae, we hypothesize that SbisCSP17 is a key candidate gene for larvae coping with soil-treated insecticides.

Animals↗