Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Functional Genomics”

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 1,027 records · Page 57Linked to original sources
PubMed2002

First insight into the genome of an uncultivated crenarchaeote from soil.

Molecular phylogenetic surveys based on the characterization of 16S rRNA genes have revealed that soil is an environment particularly rich in microbial diversity. A clade of crenarchaeota (archaea) has frequently been detected among many other novel lineages of uncultivated bacteria. In this study we have initiated a genomic approach for the characterization of uncultivated microorganisms from soil. We have developed a procedure based on a two-phase electrophoresis technique that allows the fast and reliable purification of concentrated and clonable, high molecular weight DNA. From this DNA we have constructed complex large-insert genomic libraries. Using archaea-specific 16S rRNA probes we have isolated a 34 kbp fragment from a 900 Mbp fosmid library of soil DNA. The clone contained a complete 16S/23S rRNA operon and 17 genes encoding putative proteins. Phylogenetic analyses of the rRNA genes and of several protein encoding genes (e.g. DNA polymerase, FixAB, glycosyl transferase) confirmed the specific affiliation of the genomic fragment with the non-thermophilic clade of the crenarchaeota. Content and structure of the genomic fragment indicated that the archaea from soil differ significantly from their previously studied uncultivated marine relatives. The protein encoding genes gave the first insights into the physiological potential of these organisms and can serve as a basis for future genomic and functional genomic studies.

Crenarchaeota↗
PubMed2006

Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells.

Rational engineering of complicated metabolic networks involved in the production of biologically active plant compounds has been greatly impeded by our poor understanding of the regulatory and metabolic pathways underlying the biosynthesis of these compounds. Whereas comprehensive genome-wide functional genomics approaches can be successfully applied to analyze a select number of model plants, these holistic approaches are not yet available for the study of nonmodel plants that include most, if not all, medicinal plants. We report here a comprehensive profiling analysis of the Madagascar periwinkle (Catharanthus roseus), a source of the anticancer drugs vinblastine and vincristine. Genome-wide transcript profiling by cDNA-amplified fragment-length polymorphism combined with metabolic profiling of elicited C. roseus cell cultures yielded a collection of known and previously undescribed transcript tags and metabolites associated with terpenoid indole alkaloids. Previously undescribed gene-to-gene and gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 417 gene tags and the accumulation profiles of 178 metabolite peaks. These networks revealed that the different branches of terpenoid indole alkaloid biosynthesis and various other metabolic pathways are subject to differing hormonal regulation. These networks also served to identify a select number of genes and metabolites likely to be involved in the biosynthesis of terpenoid indole alkaloids. This study provides the basis for a better understanding of periwinkle secondary metabolism and increases the practical potential of metabolic engineering of this important medicinal plant.

Catharanthus↗
PubMed2006

TcruziDB: an integrated, post-genomics community resource for Trypanosoma cruzi.

TcruziDB (http://TcruziDB.org) is an integrated post-genomics database for the parasitic organism, Trypanosoma cruzi, the causative agent of Chagas' disease. TcruziDB was established in 2003 as a flat-file database with tools for mining the unannotated sequence reads and preliminary contig assemblies emerging from the Tri-Tryp genome consortium (TIGR/SBRI/Karolinska). Today, TcruziDB houses the recently published assembled genomic contigs and annotation provided by the genome consortium in a relational database supported by the Genomics Unified Schema (GUS) architecture. The combination of an annotated genome and a relational architecture has facilitated the integration of genomic data with expression data (proteomic and EST) and permitted the construction of automated analysis pipelines. TcruziDB has accepted, and will continue to accept the deposition of genomic and functional genomic datasets contributed by the research community.

Animals↗
PubMed2003

Unfolding large-scale maps.

This is an account of the development and use of genetic maps, from humble beginnings at the hands of Thomas Hunt Morgan, to the sophistication of genome sequencing. The review charters the emergence of molecular marker maps exploiting DNA polymorphism, the renaissance of cytogenetics through the use of fluorescence in situ hybridisation, and the discovery and isolation of genes by map-based cloning. The historical significance of sequencing of DNA prefaces a section describing the sequencing of genomes, the ascendancy of particular model organisms, and the utility and limitations of comparative genomic and functional genomic approaches to further our understanding of the control of biological processes. Emphasis is given throughout the treatise as to how the structure and biological behaviour of the DNA molecule underpin the technological development and biological applications of maps.

Arabidopsis↗
PubMed2006

Screening for ligands using a generic and high-throughput light-scattering-based assay.

Rapid identification of small molecules that interact with protein targets using a generic screening method greatly facilitates the development of therapeutic agents. The authors describe a novel method for performing homogeneous biophysical assays in a high-throughput format. The use of light scattering as a method to evaluate protein stability during thermal denaturation in a 384-well format yields a robust assay with a low frequency of false positives. This novel method leads to the identification of interacting small molecules without the addition of extraneous fluorescent probes. The analysis and interpretation of data is rapid, with sensitivity for protein stability comparable to differential scanning calorimetry. The authors propose potential uses in drug discovery, structural genomics, and functional genomics as a method to evaluate small-molecule interactions, identify natural cofactors that stabilize target proteins, and identify natural substrates and products for previously uncharacterized protein targets.

Binding Sites↗
PubMed2000

[Genomic investigations in genetic cardiology: status and prospects].

The paper discusses relations of new disciplines in medical science, such as genetic cardiology and genomic medicine. It outlines today's achievements and prospects of genomic studies for some groups of cardiovascular diseases: congenital developmental defects of the heart and great vessels, cardiac arrhythmias and cardiomyopathies, and common diseases with complex inheritance, such as atherosclerosis and arterial hypertension. Accumulated knowledge on new candidate genes of these forms of pathology specifies their pathogenesis, makes it possible to outline new gene-specific therapeutical approaches, and serves as a basis for classifying risk groups by specific diseases. On the other hand, studies of the "sphere of influence" (fields of action) of genes that make up a molecular genetic basis of diseases are of fundamental value in defining the physiological role of sequenced human genomic fragments (functional genomics).

Cardiology↗
PubMed2000

[The human genome project as a scientific background of preventive medicine].

Conspicuous achievements in the Human Genome Project have already found spectacular implementation in both basic research and practice. The Human Genome Diversity, Functional Genomics, and numerous Social Programmes are under way and they are rapidly expanding the scientific area induced by the Human Genome Project. Its practical implication is mainly confined to molecular medicine and to its quickly growing area Predictive (Preventive) Medicine. The paper briefly considers the existing concepts of molecular genetic tests of "predisposition" genes, including such groups as "environmental" genes and "trigger"-genes to detect subjects highly susceptible to different common multifactorial diseases and the expediency for testing the genes whose mutations cause diseases showing their manifestations at the late stage. Evidence is provided for that there is a progressive increase in population, family, and personal predisposition gene DNA databanks. There is need for close interaction between researchers and all strata of society, including the clergy, governments, political parties, etc. in order to optimize perception of scientific achievements of modern genetics and their effective used for the welfare of mankind.

DNA↗
PubMed2001

Comparative genomics of microbial drug efflux systems.

The complete genome sequences of 36 microorganisms have now been published and this wealth of genome data has enabled the development of comparative genomic and functional genomic approaches to investigate the biology of these organisms. Comparative genomic analyses of membrane transport systems have revealed that transporter substrate specificities correlate with an organism's lifestyle. The types and numbers of predicted drug efflux systems vary dramatically amongst sequenced organisms. Microarray and gene knockout studies to date have suggested that predicted drug efflux genes often appear to be a) non-essential and b) expressed at detectable levels under standard laboratory growth conditions.

Bacteria↗
PubMed2002

[Experimental study on an auditory method for analyzing DNA segments].

To explore a new method for analyzing biological molecules that have already been sequenced, an experimental study on an auditory method was carried out. The auditory method for analyzing biological molecules includes audible representation of sequence data. Audible representation of sequence data was implemented by using a multimedia computer. Each mononucleotide in a DNA sequence was matched with a corresponding sound, i.e., a DNA sequence was "dubbed" in a sound sequence. When the sound sequence is played, a special cadence can be heard. In the audible representation experiment, special cadences of different exons can be clearly heard. The results show that audible representation of DNA sequence data can be implemented by using a multimedia technique. After a 5-time auditory training, subjects both in internal testing and external testing can obtain 93%-100% of judgment accuracy rate for the difference between two sound sequences of two different exons, thus providing an experimental basis for the practicability of this method. Auditory method for analyzing DNA segments might be beneficial for the research in comparative genomics and functional genomics. This new technology must be robust and be carefully evaluated and improved in a high-throughput environment before its implementation in an application setting.

Computational Biology↗
PubMed2002

APBioNet: the Asia-Pacific regional consortium for bioinformatics.

Bioinformatics and computational biology, along with the related fields of genomics, proteomics, functional genomics and systems biology are new wave scientific disciplines that harness composite computational power across networks to advance biological knowledge at the most basic level and to direct traditional laboratory-based research efforts in the biomedical sciences. 'Fostering the growth of bioinformatics and allied disciplines in the Asia-Pacific region' is the motto of the first regional bioinformatics society, the Asia-Pacific Bioinformatics Network (APBioNet). APBioNet addresses the issues of hardware, software, databases and networks pertaining to bioinformatics, with the additional layer of pertinent education, training and research. Recent milestones achieved include hosting an international bioinformatics symposium in Asia and setting up large-scale regional grid-computing projects.

Asia↗
PubMed2006

Origin of the tetraspanin uroplakins and their co-evolution with associated proteins: implications for uroplakin structure and function.

Genome level information coupled with phylogenetic analysis of specific genes and gene families allow for a better understanding of the structure and function of their protein products. In this study, we examine the mammalian uroplakins (UPs) Ia and Ib, members of the tetraspanin superfamily, that interact with uroplakins UPII and UPIIIa/IIIb, respectively, using a phylogenetic approach of these genes from whole genome sequences. These proteins interact to form urothelial plaques that play a central role in the permeability barrier function of the apical urothelial surface of the urinary bladder. Since these plaques are found exclusively in mammalian urothelium, it is enigmatic that UP-like genomic sequences were recently found in lower vertebrates without a typical urothelium. We have cloned full-length UP-related cDNAs from frog (Xenopus laevis), chicken (Gallus gallus), and zebrafish (Danio rerio), and combined these data with sequence information from their orthologs in all the available fully sequenced and annotated animal genomes. Phylogenetic analyses of all the available uroplakin sequences, and an understanding of their distribution in several animal taxa, suggest that: (i) the UPIa/UPIb and UPII/UPIII genes evolved by gene duplication in the common ancestor of vertebrates; (ii) uroplakins can be lost in different combinations in vertebrate lineages; and (iii) there is a strong co-evolutionary relationship between UPIa and UPIb and their partners UPII and UPIIIa/IIIb, respectively. The co-evolution of the tetraspanin UPs and their associated proteins may fine-tune the structure and function of uroplakin complexes enabling them to perform diverse species- and tissue-specific functions. The structure and function of uroplakins, which are also expressed in Xenopus kidney, oocytes and fat body, are much more versatile than hitherto appreciated.

Amino Acid Sequence↗
PubMed2002

The C-terminal region of mitochondrial single-subunit RNA polymerases contains species-specific determinants for maintenance of intact mitochondrial genomes.

Functional conservation of mitochondrial RNA polymerases was investigated in vivo by heterologous complementation studies in yeast. It turned out that neither the full-length mitochondrial RNA polymerase of Arabidopsis thaliana, nor a set of chimeric fusion constructs from plant and yeast RNA polymerases can substitute for the yeast mitochondrial core enzyme Rpo41p when expressed in Deltarpo41 yeast mutants. Mitochondria from mutant cells, expressing the heterologous mitochondrial RNA polymerases, were devoid of any mitochondrial genomes. One important exception was observed when the carboxyl-terminal domain of Rpo41p was exchanged with its plant counterpart. Although this fusion protein could not restore respiratory function, stable maintenance of mitochondrial petite genomes (rho(-))(-) was supported. A carboxyl-terminally truncated Rpo41p exhibited a comparable activity, in spite of the fact that it was found to be transcriptionally inactive. Finally, we tested the carboxyl-terminal domain for complementation in trans. For this purpose the last 377 amino acid residues of yeast mitochondrial Rpo41p were fused to its mitochondrial import sequence. Coexpression of this fusion protein with C-terminally truncated Rpo41p complemented the Deltarpo41 defect. These data reveal the importance of the carboxyl-terminal extension of Rpo41p for stable maintenance of intact mitochondrial genomes and for distinct species-specific intramolecular protein-protein interactions.

Arabidopsis↗
PubMed1998

A genome-wide functional assay of signal transduction in living mammalian cells.

We describe a genome-wide functional assay for rapid isolation of cell clones and genetic elements responsive to specific stimuli. A promoterless beta-lactamase reporter gene was transfected into a human T-cell line to generate a living library of reporter-tagged clones. When loaded with a cell-permeable fluorogenic substrate, the cell library simultaneously reports the expression of a large number of endogenous genes. Flow cytometry was used to recover individual clones whose reporter-tagged genes were either induced or repressed following T-cell activation. Responsive clones were expanded and analyzed pharmacologically to identify patterns of regulation associated with specific genes. Although demonstrated using T cells, the genomic assay could be applied to map downstream transcriptional consequences for any propagating cell line in response to any stimulus of interest.

Cell Separation↗
PubMed2026

[Applications and Challenges of Deep Learning in Human Genome Research].

In recent years, the advent of high-throughput omics technologies has fueled an explosive growth in human genomic data. Uncovering the latent functions within this vast data has become a significant challenge in functional genomics research. While traditional statistical methods have proved successful for analyzing smaller-scale datasets in the past, they exhibit clear limitations in analytical efficiency and integrating multi-dimensional data, struggling to meet the escalating demands of contemporary genomic analysis. The introduction of deep learning (DL) technologies offers a novel paradigm for this field. This review systematically examines the advances in applying deep learning to human genomics research. Studies demonstrate that when ample labeled data is available, discriminative DL computational methods-such as Convolutional Neural Networks (CNNs) and Long Short-Term Memory networks (LSTMs)-achieve high accuracy and efficiency in genomic variant discovery tasks. Furthermore, generative DL methods, particularly Large Language Models (LLMs) leveraging self-supervised pre-training strategies, effectively integrate complex genomic information and exhibit superior performance in functional genomic sequence annotation and gene regulation studies. This review also explores the application of LLMs in multi-omics data integration and prediction. Looking ahead, the continued accumulation of long-read sequencing and high-dimensional data is expected to enable DL technologies to integrate increasingly complex and heterogeneous genomic information, playing an increasingly crucial role in human genomics research.

Deep Learning↗
PubMed2003

Experimental evolution yields hundreds of mutations in a functional viral genome.

Two lines of the bacteriophage T7 were grown to fix mutations indiscriminately, using a combination of population bottlenecks and mutagenesis. Complete genome sequences revealed 404 and 299 base substitutions in the two lines, the largest number characterized in functional microbial genomes so far. Missense substitutions outnumbered silent substitutions. Silent substitutions occurred at similar rates between essential and nonessential genes, but missense substitutions occurred at a higher rate in nonessential genes than in essential genes, as expected if they were less deleterious in the nonessential genes. Viral fitness declined during this protocol, and subsequent passaging of each mutated line in large population sizes restored some of the lost fitness. Substitution levels during these recoveries were less than 6% of those during the bottleneck phase, and only two changes during recovery were reversions of the original mutations. Exchanges of genomic fragments between the two recovered lines revealed that fitness effects of some substitutions were not additive-that interactions were accumulating which could lead to incompatibility between the diverged genomes. Based on these results, unprecedented high rates of nucleotide and functional divergence in viral genomes should be attainable experimentally by using repeated population bottlenecks at a high mutation rate interspersed with recovery.

Bacteriophage T7↗
PubMed2002

Role for NMR in structural genomics.

The 2nd EMSL Workshop on Structural Genomics was held on 28th and 29th July 2000 at the Environmental Molecular Sciences Laboratory at the Department of Energy's Pacific Northwest National Laboratory in Richland, WA. The workshop focused on four topics: 1. The role for NMR in structural and functional genomics; 2. The technical challenges NMR faces for structural and functional genomics; 3. The potential need for a national NMR center for structural and functional genomics in the United States; and 4. Organization of the NMR community. This report summarizes the workshop proceedings and conclusions reached regarding the role of NMR in the emerging fields of structural and functional genomics.

Academies and Institutes↗
PubMed2004

Impact of 'ome' analyses on inverse metabolic engineering.

Genome-wide or large-scale methodologies employed in functional genomics such as DNA sequencing, transcription profiling, proteomics, and metabolite profiling have become important tools in many metabolic engineering strategies. These techniques allow the identification of genetic differences and insight into their cellular effects. In the field of inverse metabolic engineering mapping of differences between strains with different degree of a certain desired phenotype and subsequent identification of factors conferring that phenotype are an essential part. Therefore, the tools of functional genomics in particular have the potential to promote and expand inverse metabolic engineering. Here, we review the use of functional genomics methods in inverse metabolic engineering, examples are presented, and we discuss the identification of targets for metabolic engineering with low fold changes using these techniques.

Animals↗