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 757 records · Page 42Linked to original sources
PubMed2006

SIGMA: a system for integrative genomic microarray analysis of cancer genomes.

BACKGROUND: The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. RESULTS: We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. CONCLUSION: In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA) of cancer genomes, can be accessed at http://sigma.bccrc.ca.

Adenocarcinoma↗
PubMed2000

Metabolite profiling for plant functional genomics.

Multiparallel analyses of mRNA and proteins are central to today's functional genomics initiatives. We describe here the use of metabolite profiling as a new tool for a comparative display of gene function. It has the potential not only to provide deeper insight into complex regulatory processes but also to determine phenotype directly. Using gas chromatography/mass spectrometry (GC/MS), we automatically quantified 326 distinct compounds from Arabidopsis thaliana leaf extracts. It was possible to assign a chemical structure to approximately half of these compounds. Comparison of four Arabidopsis genotypes (two homozygous ecotypes and a mutant of each ecotype) showed that each genotype possesses a distinct metabolic profile. Data mining tools such as principal component analysis enabled the assignment of "metabolic phenotypes" using these large data sets. The metabolic phenotypes of the two ecotypes were more divergent than were the metabolic phenotypes of the single-loci mutant and their parental ecotypes. These results demonstrate the use of metabolite profiling as a tool to significantly extend and enhance the power of existing functional genomics approaches.

Arabidopsis↗
PubMed2005

Influence of low glycolytic activities in gcr1 and gcr2 mutants on the expression of other metabolic pathway genes in Saccharomyces cerevisiae.

A complex of the transcription factors Gcr1p and Gcr2p coordinately regulates the expression of glycolytic genes in Saccharomyces cerevisiae. To understand the effects of gcr mutations on other metabolic pathways, genome-wide gene expression profiles in gcr1 and gcr2 mutants were examined. The biggest effects of gcr1 and gcr2 mutations were observed on the glycolytic genes and the expressions of most of the glycolytic genes were substantially decreased compared to those in the wild-type strain in both glucose and glycerol+lactate growth conditions. On the other hand, the expressions of genes encoding the TCA cycle and respiration were increased in gcr mutants when the cells were grown in glucose. RT-PCR analyses revealed that the expression of SIP4 and HAP5, which are known to affect the expression of some of the gluconeogenic, TCA cycle and respiratory genes, were also increased under this condition. The growth of gcr mutants on glucose was impaired by adding respiration inhibitor antimycin A, whereas the growth of the wild-type strain was not. The conversion of glucose to biomass was higher and, to the contrary, ethanol yield was lower in the gcr2 mutant compared to those in the wild-type strain. These results suggest the possibility that the gcr mutants, in which glycolytic activities are low, changed their metabolic patterns under glucose growth condition to enhance the expression of TCA cycle and respiratory genes to produce more energy.

Adenosine Triphosphate↗
PubMed2006

The problem of neuronal cell types: a physiological genomics approach.

Neural circuits within the vertebrate brain are composed of highly diverse cell types. The exact extent of this diversity is a matter of continuing debate. For example, do cortical interneurons comprise a few, dozens or >100 distinct cell types? Recently, several groups have used microarrays to measure genome-wide gene expression profiles for specific neuronal cell types. These methods can offer an objective basis for neuronal classification. In this review, we argue that this approach should now be carried out more broadly and that it should be coupled to large-scale efforts to generate mouse driver lines in which tools for genetic manipulation, such as the Cre recombinase, are expressed in identified cell types within the brain. This would enable neuroscientists to begin to investigate more systematically the roles of specific genes in establishing particular cellular phenotypes, and also the roles of particular cell types within brain circuits. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Animals↗
PubMed2005

High-resolution genome-wide mapping of genetic alterations in human glial brain tumors.

High-resolution genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. We have done such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. This gene-by-gene approach permitted the precise sizing of critical amplicons and deletions and the detection of multiple new genetic aberrations. It has also revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations was shown predominantly associated with either astrocytic or oligodendrocytic tumor phenotype. Finally, five novel minimally deleted regions were identified in a subset of tumors, containing putative candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role in gliomagenesis.

Brain Neoplasms↗
PubMed2002

Microarray analysis of rat chromosome 2 congenic strains.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of human essential hypertension, and a number of reproducible blood pressure regulation quantitative trait loci have been found to map to rat chromosome 2. The SP.WKYGla2c* congenic strain was produced by introgressing a region of rat chromosome 2 from the normotensive Wistar Kyoto (WKY) strain into the genetic background of the SHRSP. Systolic and diastolic blood pressures were significantly reduced in the SP.WKYGla2c* compared with the SHRSP parental strain (198/134+/-6.1/3.3 versus 172/120+/-3.8/3.4 mm Hg; F=15.8/8.1, P=0.0009/0.013). Genome-wide microarray expression profiling was undertaken to identify differentially expressed genes among the parental SHRSP, WKY, and congenic strain. We identified a significant reduction in expression of glutathione S-transferase mu-type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription-polymerase chain reaction relative to a beta-actin standard confirmed the microarray results with SHRSP mRNA at 8.56 x 10(-4) +/-1.6 x 10(-4) compared with SP.WKYGla2c* 3.67 x 10(-3)+/-2.8 x 10(-4) (95% CI -3.9 x 10(-3) to -1.8 x 10(-3); P=0.0034) and WKY 4.03 x 10(-3)+/-5.1 x 10(-4); (95% CI -5.4 x 10(-3) to -8.9 x 10(-4); P=0.027). We also identified regions of conserved synteny, each containing the Gstm2 gene, on mouse chromosome 3 and human chromosome 1.

Animals↗
PubMed2002

Genome-wide analysis of gene expression in synovial sarcomas using a cDNA microarray.

Among a histologically heterogeneous group of soft tissue sarcomas, synovial sarcoma (SS) is regarded as a "miscellaneous" entity of uncertain origin. Although recent molecular analysis has disclosed involvement of a specific chromosomal translocation in the pathogenesis of SS, its genetic features remain largely unclear. In the work reported here we examined genome-wide gene expression profiles of 13 SS cases and 34 other spindle-cell sarcoma cases by cDNA microarray consisting of 23,040 genes. A hierarchical clustering analysis grouped SS and malignant peripheral nerve sheath tumor into the same category, and these two types of tumor shared expression patterns of numerous genes relating to neural differentiation. Several genes were up-regulated in almost all SS cases, and the presumed functions of known genes among them were related to migration or differentiation of neural crest cells, suggesting the possibility of neuroectodermal origin of SS. Moreover, we identified a set of genes that divided SS cases into two putative subclasses, a feature that may shed light on novel biological aspects of SS in addition to those having to do with epithelial differentiation. These data have provided clues for understanding the origin and tumorigenesis of SS.

Cluster Analysis↗
PubMedDate not supplied

[The specific serological profile in hepatitis B virus infection in children].

UNLABELLED: Hepatitis B virus infection (HBV) has a very well known specific serologic profile. In the last years the molecular biology methods reveal some "particular serological profiles" by genomic mutation. One particular profile consists in the absence of anti-HBc total antibodies simultaneously with the presence of HBsAg. Our tested group consists of 372 children aged 0.1 to 15 years. The presence of HBsAg was determined by ELISA "sandwich" and confirmed by neutralisation test. For HIV infection we used two ELISA tests (competitive and indirect) and the Western Blot test for confirmation. Of the total, there were 13 children HBsAg positive and without anti-HBc antibody (3.49% respectively), 7 of the 13 children (53.8%) were dystrophic and 4 were HIV positive (30.76%). From 372 cases, 104 were HBsAg positive (27.9%) and 53 (14.2%) of them had chronic hepatitis. CONCLUSIONS: 1. The particular serologic profile requires the testing of all serological markers specific for HBV. 2. This particular serologic profile is correlated with HIV positive status and dystrophy.

Adolescent↗
PubMed2026

ChromCall: assigning chromatin status to defined genomic regions using epigenomic profiling data.

MOTIVATION: Chromatin regulation is crucial for modulating gene expression and cellular function by altering DNA accessibility. Defining and understanding chromatin regulation across diverse biological conditions, including health and disease, requires quantification of both the presence and enrichment level of diverse DNA-binding factors and chromatin modifications across defined genomic regions. Existing approaches mainly rely on peak-based or genome-wide models, which identify high-signal regions but do not annotate chromatin status at predefined functional genomic regions, such as promoters or enhancers. This lack of region-based annotation limits downstream comparative and integrative analyses across multiple factors and datasets, prompting us to create ChromCall. RESULTS: ChromCall is an R package for region-based chromatin enrichment analysis that provides a robust and extensible foundation for transparent and reproducible epigenomic profiling at predefined genomic regions. We applied ChromCall to ChIP-seq data from glioblastoma (GBM) brain tumours and found that the promoters of genes implicated in treatment resistance are significantly more likely to exhibit a combination of histone marks associated with phenotypic plasticity. This highlights a potential novel mechanism of therapeutic escape in these deadly tumours. AVAILABILITY AND IMPLEMENTATION: The R package is available on https://github.com/GliomaGenomics/ChromCall and the version used in this paper is archived at https://doi.org/10.5281/zenodo.19580967.

Chromatin↗
PubMed2005

Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks.

A major challenge in drug discovery is to distinguish the molecular targets of a bioactive compound from the hundreds to thousands of additional gene products that respond indirectly to changes in the activity of the targets. Here, we present an integrated computational-experimental approach for computing the likelihood that gene products and associated pathways are targets of a compound. This is achieved by filtering the mRNA expression profile of compound-exposed cells using a reverse-engineered model of the cell's gene regulatory network. We apply the method to a set of 515 whole-genome yeast expression profiles resulting from a variety of treatments (compounds, knockouts and induced expression), and correctly enrich for the known targets and associated pathways in the majority of compounds examined. We demonstrate our approach with PTSB, a growth inhibitory compound with a previously unknown mode of action, by predicting and validating thioredoxin and thioredoxin reductase as its target.

Algorithms↗
PubMed2005

Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling.

Chemical genomics aims to discover small molecules that affect biological processes through the perturbation of protein function. However, determining the protein targets of bioactive compounds remains a formidable challenge. We address this problem here through the creation of a natural product-inspired small-molecule library bearing protein-reactive elements. Cell-based screening identified a compound, MJE3, that inhibits breast cancer cell proliferation. In situ proteome reactivity profiling revealed that MJE3, but not other library members, covalently labeled the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), resulting in enzyme inhibition. Interestingly, MJE3 labeling and inhibition of PGAM1 were observed exclusively in intact cells. These results support the hypothesis that cancer cells depend on glycolysis for viability and promote PGAM1 as a potential therapeutic target. More generally, the incorporation of protein-reactive compounds into chemical genomics screens offers a means to discover targets of bioactive small molecules in living systems, thereby enabling downstream mechanistic investigations.

Antineoplastic Agents↗
PubMed2026

cgDist: Nucleotide-level distance calculation from cgMLST allelic profiles.

Bacterial genomic surveillance requires balancing computational efficiency with genetic resolution for effective cluster investigation. cgMLST distance calculations treat all allelic differences as equivalent units, obscuring nucleotide-level variation. Furthermore, single nucleotide polymorphism-based pipelines provide finer resolution at substantially higher computational cost, which limits their routine deployment in surveillance laboratories. We present cgDist, an algorithm that calculates nucleotide-level distances directly from cgMLST allelic profiles, providing finer resolution than allele-count distances by leveraging within-allele nucleotide variation. The cache architecture stores alignment statistics, enabling distance calculation modes without computation and supporting both dataset-specific and schema-complete cache generation. This design enables incremental surveillance analysis, with performance benefits as laboratories accumulate alignment data. cgDist functions as a precision 'zoom lens' for the investigation of clusters identified through initial cgMLST screening. Rather than restructuring population relationships, this targeted approach concentrates enhanced resolution where it is most informative. The algorithm ensures that cgDist distances are greater than or equal to corresponding cgMLST distances, preserving epidemiological interpretability while adding genetic discrimination. By increasing resolution within identified clusters, cgDist may also support outbreak investigation, a potential application that remains to be evaluated on outbreak-derived data.

Algorithms↗
PubMed2004

Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.

MOTIVATION: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression. RESULTS: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15< tau<0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the I(B) tissues in which it is overly expressed, and the 12-I(B) tissues in which it shows low expression. The 85 dominant midrange patterns with I(B)=2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny. AVAILABILITY: All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803. CONTACT: doron.lancet@weizmann.ac.il SUPPLEMENTARY INFORMATION: Four tables available at the above site.

Algorithms↗
PubMed2004

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

Carcinoma in Situ↗
PubMed2002

Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing.

Replication of the genome before mitotic cell division is a highly regulated process that ensures the fidelity of DNA duplication. DNA replication initiates at specific locations, termed origins of replication, and progresses in a defined temporal order during the S phase of the cell cycle. The relationship between replication timing and gene expression has been the subject of some speculation. A recent genome-wide analysis in Saccharomyces cerevisiae showed no association between replication timing and gene expression. In higher eukaryotes, the limited number of genomic loci analyzed has not permitted a firm conclusion regarding this association. To explore the relationship between DNA replication and gene expression in higher eukaryotes, we developed a strategy to measure the timing of DNA replication for thousands of genes in a single DNA array hybridization experiment. Using this approach, we generated a genome-wide map of replication timing for Drosophila melanogaster. Moreover, by surveying over 40% of all D. melanogaster genes, we found a strong correlation between DNA replication early in S phase and transcriptional activity. As this correlation does not exist in S. cerevisiae, this interplay between DNA replication and transcription may be a unique characteristic of higher eukaryotes.

Animals↗
PubMed2005

Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling.

PURPOSE: Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), can improve the resectability of larger neoplasms for some patients and offer a better prognosis. However, some suffer severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting response to the M-VAC therapy. EXPERIMENTAL DESIGN: We analyzed gene expression profiles of biopsy materials from 27 invasive bladder cancers using a cDNA microarray consisting of 27,648 genes, after populations of cancer cells had been purified by laser microbeam microdissection. RESULTS: We identified dozens of genes that were expressed differently between nine "responder" and nine "nonresponder" tumors; from that list we selected the 14 "predictive" genes that showed the most significant differences and devised a numerical prediction scoring system that clearly separated the responder group from the nonresponder group. This system accurately predicted the drug responses of 8 of 9 test cases that were reserved from the original 27 cases. Because real-time reverse transcription-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative reverse transcription-PCR-based prediction system that could be feasible for routine clinical use. CONCLUSIONS: Our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

Aged↗
PubMed2006

Genome-wide gene expression profile analysis of esophageal squamous cell carcinomas.

To identify the molecules involved in esophageal carcinogenesis and those applicable as novel tumor markers and for the development of new molecular therapies, we performed gene expression profile analysis of 19 esophageal squamous cell carcinoma (ESCC) cells purified by laser microbeam microdissection (LMM). Using a cDNA microarray representing 32,256 genes, we identified 147 genes that were commonly up-regulated and 376 transcripts that were down-regulated in ESCC cells compared with non-cancerous esophageal epithelial cells. A comparison of clinicopathological data with the expression profiles of the 19 ESCCs identified 20 genes whose expression levels could most significantly separate cases with lymph node metastasis from those without. In addition, immunohistochemical analysis of candidate tumor markers on tissue microarrays demonstrated transactivation of a secretory protein, transforming growth factor alpha (TGFA) in the great majority of 228 ESCC cases and an association of their expression with the poor prognosis of patients. Our data provide valuable information for establishing novel diagnostic markers for early diagnosis and choice of therapy, and identifying therapeutic target molecules for the development of novel anti-cancer drugs and immunotherapy in esophageal cancer treatment.

Aged↗