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At least 469 records · Page 26Linked to original sources
PubMed2002

HOX Pro DB: the functional genomics of hox ensembles.

The HOX Pro database contains information about the organization, function and evolution of gene ensembles, notably the homeobox-containing genes. It is now clear that a subset of genes containing the homeobox motif play key roles in the orchestration of genes which control embryonic patterning, morphogenesis, cell differentiation and malignant transformation. The HOX Pro contains a broad spectrum of information including images, diagrams and animations. Currently this amounts to approximately 700 HTML pages together with 400 images which contain information on 200 groups of genes and 90 promoters, in turn linked to maps of 13 HOX clusters and nine genetic networks. There are about 700 sequences of individual hox-genes of animals classified in approximately 200 homologous or paralogous groups. Graphical representation of HOX clusters and Hox-based networks is accomplished by means of flow and 3D diagrams, JavaScript animations and Java applets. The HOX Pro now includes sections presenting data mining and data simulation issues. The DB is located at http://www.iephb.nw.ru/hoxpro.

Animals↗
PubMed2001

Random antisense cDNA mutagenesis as an efficient functional genomic approach in higher plants.

Most cellular processes in an organism depend on functions of expressed sequences. Thus, efficient large-scale functional assignment of expressed sequences is crucial for understanding cellular processes. Towards this goal in plants, we designed a "random antisense cDNA mutagenesis (RAM)" approach. In a pilot experiment, 1,000 transgenic plants of Arabidopsis thaliana (L.) Heynh. (ecotype Wassilevskija) expressing random antisense cDNA(s) were generated from Agrobacterium cultures harboring an Arabidopsis antisense cDNA library. We identified 104 mutant lines from the transgenic pool by visual screening. Genetic analysis suggested that 37% of the mutations were likely due to antisense effects. When the cDNA inserts were isolated from 11 mutant lines by polymerase chain reaction and reintroduced into plants to express the antisense transcripts, the original mutant phenotypes were reproduced in 7 cDNA clones. One of the cDNA clones did not generate a database match to any sequence with known functions, but did have a dramatic effect on the architecture of the inflorescence in the antisense transgenic plants. Through the RAM approach, it should be possible to assign a large number of expressed sequences to known in vivo functions in plants.

Arabidopsis↗
PubMed1999

Human phosphoribosylformylglycineamide amidotransferase (FGARAT): regional mapping, complete coding sequence, isolation of a functional genomic clone, and DNA sequence analysis.

Purines play essential roles in many cellular functions, including DNA replication, transcription, intra- and extra-cellular signaling, energy metabolism, and as coenzymes for many biochemical reactions. The de-novo synthesis of purines requires 10 enzymatic steps for the production of inosine monophosphate (IMP). Defects in purine metabolism are associated with human diseases. Further, many anticancer agents function as inhibitors of the de-novo biosynthetic pathway. Genes or cDNAs for most of the enzymes comprising this pathway have been isolated from humans or other mammals. One notable exception is the phosphoribosylformylglycineamide amidotransferase (FGARAT) gene, which encodes the fourth step of this pathway. This gene has been cloned from numerous microorganisms and from Drosophila melanogaster and C. elegans. We report here the identification of a human cDNA containing the coding region of the FGARAT mRNA and the isolation of a P1 clone that contains an intact human FGARAT gene. The P1 clone corrects the purine auxotrophy and protein deficiency of Chinese hamster ovary (CHO) cell mutants (AdeB) deficient in both the activity and the protein for FGARAT. The P1 clone was used to regionally map the FGARAT gene to chromosome region 17p13, a location consistent with our prior assignment of this gene to chromosome 17. A comparison of the DNA sequence of the human FGARAT and FGARAT DNA sequence from 17 other organisms is reported. The isolation of this gene means that DNA clones for all the 10 steps of IMP synthesis have been isolated from humans or other mammals.

Amino Acid Sequence↗
PubMed2005

Functional genomics of cardiac ion channel genes.

Ion channels are an ensemble of specialized membrane proteins that act in concert to create and modulate the electrical activity of many excitable cells, including cardiac myocytes. Following completion of the sequencing of various genomes, including that of the human, the complete repertoire of ion channel genes has been elucidated for different species. How transcripts issued from this gene collection are expressed and modulated in relation to variable physiological and pathological situations is the subject of functional or physiological genomics. Specialized microarrays (IonChips) comprising probes for the ensemble of ion channel and regulatory genes were developed as an alternative to whole-genome DNA chips. Physiological genomics of cardiac ion channel genes is a growing field that, in combination with genetics, should markedly increase our comprehension of the molecular mechanisms leading to arrhythmias.

Amiodarone↗
PubMed2003

Metabolite profiling as a functional genomics tool.

Plants accumulate a very large number of small molecules (phytochemicals) with important functions in the ecology of plants and in the protection against biotic and abiotic stress conditions. Little is known on how phytochemical biosynthetic pathways are regulated, which is a key step to successfully engineering plant metabolism. Plant natural products are usually not essential, and genetic analyses often fail to identify phenotypes associated with the absence of these compounds. We have investigated the use of metabolite profiling of plant cells in culture to establish the function of transcription factors suspected to control plant metabolic pathways.

Cell Culture Techniques↗
PubMed2004

RNAi in functional genomics.

There has been a lack of powerful tools for systematic analysis of mammalian gene function, but RNA interference (RNAi) may now provide such a strategy. Stable transcription of RNAi triggers from suitable expression cassettes integrated into the host cell genome by viral gene transfer can induce long-term and heritable gene silencing in mammalian cells. However, the use of RNAi as a genetic tool is limited by difficulties in identifying efficient RNAi triggers, the problem of effective delivery and off-target effects, as well as potential genotoxic side effects of viral gene transfer strategies. Recent insights into the molecular mechanisms of silencing processes mediated by either siRNA or miRNA will allow further optimization of RNAi triggers as genetic tools.

Animals↗
PubMed2005

MIPS bacterial genomes functional annotation benchmark dataset.

MOTIVATION: Any development of new methods for automatic functional annotation of proteins according to their sequences requires high-quality data (as benchmark) as well as tedious preparatory work to generate sequence parameters required as input data for the machine learning methods. Different program settings and incompatible protocols make a comparison of the analyzed methods difficult. RESULTS: The MIPS Bacterial Functional Annotation Benchmark dataset (MIPS-BFAB) is a new, high-quality resource comprising four bacterial genomes manually annotated according to the MIPS functional catalogue (FunCat). These resources include precalculated sequence parameters, such as sequence similarity scores, InterPro domain composition and other parameters that could be used to develop and benchmark methods for functional annotation of bacterial protein sequences. These data are provided in XML format and can be used by scientists who are not necessarily experts in genome annotation. AVAILABILITY: BFAB is available at http://mips.gsf.de/proj/bfab

Bacterial Proteins↗
PubMed2002

Functional genomics approaches for the identification and validation of antifungal drug targets.

So far, antifungal drug discovery seems to have benefited little from the enormous advances in the field of genomics in the last decade. Although it has become clear that traditional drug screening is not delivering the long-awaited novel potent antifungals, little has been reported on efforts to use novel genome-based methodologies in the quest for new drugs acting on human pathogenic fungi. Although the market for a novel systemic and even topical broad-spectrum antifungal appears considerable, many large pharmaceutical companies have decided to scale back their activities in antifungal drug discovery. Here we report on some of the recent advances in genomics-based technologies that will allow us not only to identify and validate novel drug targets but hopefully also to discover active therapeutic agents. Novel drug targets have already been found by 'en masse' gene inactivation strategies (e.g. using antisense RNA inhibition). In addition, genome expression profiling using DNA microarrays helps to assign gene function but also to understand better the mechanism of action of known drugs (e.g. itraconazole) and to elucidate how new drug candidates work. No doubt, we have a long way to go just to catch up with the advances made in other therapeutic areas, but all tools are at hand to derive practical benefits from the genomics revolution. The next few years should prove a very exciting time in the history of antifungal drug discovery.

Animals↗
PubMed2002

Functional genomics of parasitic worms: the dawn of a new era.

The study of gene function in parasitic worms is technically demanding due to difficulties associated with life-cycle propagation and, hence, molecular genetics. Exploitation of the free-living nematode, Caenorhabditis elegans, coupled with recent major advances in molecular studies of parasitic nematodes, have opened up new avenues for understanding the biology of these parasites and present opportunities for novel strategies of therapeutic intervention and control.

Animals↗
PubMed2003

Hitchhiking mapping--functional genomics from the population genetics perspective.

Several statistical tests based on population genetic theory are used to identify genes that have recently acquired a beneficial mutation. Here, I describe the extension of these tests to a multilocus approach for a genome-wide survey for genes that have been under recent positive selection. As this strategy could potentially identify genes with weak phenotypic effects, it will be very useful in population genetic approaches aimed at understanding adaptation processes in natural populations. Furthermore, this 'hitchhiking mapping' could also help in the functional characterization of genomes.

Animals↗
PubMed2002

Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics.

Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVM(light). Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms.

Algorithms↗
PubMed2006

MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics.

BACKGROUND: The genome sequencing projects have shown our limited knowledge regarding gene function, e.g. S. cerevisiae has 5-6,000 genes of which nearly 1,000 have an uncertain function. Their gross influence on the behaviour of the cell can be observed using large-scale metabolomic studies. The metabolomic data produced need to be structured and annotated in a machine-usable form to facilitate the exploration of the hidden links between the genes and their functions. DESCRIPTION: MeMo is a formal model for representing metabolomic data and the associated metadata. Two predominant platforms (SQL and XML) are used to encode the model. MeMo has been implemented as a relational database using a hybrid approach combining the advantages of the two technologies. It represents a practical solution for handling the sheer volume and complexity of the metabolomic data effectively and efficiently. The MeMo model and the associated software are available at http://dbkgroup.org/memo/. CONCLUSION: The maturity of relational database technology is used to support efficient data processing. The scalability and self-descriptiveness of XML are used to simplify the relational schema and facilitate the extensibility of the model necessitated by the creation of new experimental techniques. Special consideration is given to data integration issues as part of the systems biology agenda. MeMo has been physically integrated and cross-linked to related metabolomic and genomic databases. Semantic integration with other relevant databases has been supported through ontological annotation. Compatibility with other data formats is supported by automatic conversion.

Computer Simulation↗
PubMed2005

VIS-O-BAC: exploratory visualization of functional genome studies from bacteria.

UNLABELLED: The visualization-aided exploration of complex datasets will allow the research community to formulate novel functional hypotheses leading to a better understanding of biological processes at all levels. Therefore, we have developed a web resource termed VIS-O-BAC designed for the functional investigation of expression data for model systems, such as bacterial pathogens based on a graphical display. Genome-scale datasets derived from typical 'omic' approaches can directly be explored with respect to three biologically relevant aspects, the genome structure (operon organization), the organization of genes in pathways (KEGG) and the gene function with Gene Ontology (GO) terms. The integrated viewers can be used in parallel and combine expression data and functional annotations from different external data repositories. The graphical visualizations evidently accelerate both the validation of regulatory information and the detection of affected biological processes. AVAILABILITY: http://leger2.gbf.de/cgi-bin/vis-o-bac.pl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chromosome Mapping↗
PubMed2001

T-DNA-associated duplication/translocations in Arabidopsis. Implications for mutant analysis and functional genomics.

T-DNA insertion mutants have become a valuable resource for studies of gene function in Arabidopsis. In the course of both forward and reverse genetic projects, we have identified novel interchromosomal rearrangements in two Arabidopsis T-DNA insertion lines. Both rearrangements were unilateral translocations associated with the left borders of T-DNA inserts that exhibited normal Mendelian segregation. In one study, we characterized the embryo-defective88 mutation. Although emb88 had been mapped to chromosome I, molecular analysis of DNA adjacent to the T-DNA left border revealed sequence from chromosome V. Simple sequence length polymorphism mapping of the T-DNA insertion demonstrated that a >40-kbp region of chromosome V had inserted with the T-DNA into the emb88 locus on chromosome I. A similar scenario was observed with a prospective T-DNA knockout allele of the LIGHT-REGULATED RECEPTOR PROTEIN KINASE (LRRPK) gene. Whereas wild-type LRRPK is on lower chromosome IV, mapping of the T-DNA localized the disrupted LRRPK allele to chromosome V. In both these cases, the sequence of a single T-DNA-flanking region did not provide an accurate picture of DNA disruption because flanking sequences had duplicated and inserted, with the T-DNA, into other chromosomal locations. Our results indicate that T-DNA insertion lines--even those that exhibit straightforward genetic behavior--may contain an unexpectedly high frequency of rearrangements. Such duplication/translocations can interfere with reverse genetic analyses and provide misleading information about the molecular basis of mutant phenotypes. Simple mapping and polymerase chain reaction methods for detecting such rearrangements should be included as a standard step in T-DNA mutant analysis.

Arabidopsis↗
PubMed2002

Functional genomics in the mouse.

The mouse is the premier genetic model organism for the study of human disease and development. With the recent advances in sequencing of the human and mouse genomes, there is strong interest now in large-scale approaches to decipher the function of mouse genes using various mutagenesis technologies. This review discusses what tools are currently available for manipulating and mutagenizing the mouse genome, such as ethylnitrosourea and gene trap mutagenesis, engineered inversions and deletions using the cre-lox system, and proviral insertional mutagenesis in somatic cells, and how these are being used to uncover gene function.

Alkylating Agents↗
PubMed2003

Protein structure prediction and analysis as a tool for functional genomics.

Bioinformatic analyses of whole genome sequences highlight the problem of identifying the biochemical and cellular functions of the many gene products that are at present uncharacterised. Determination of their three-dimensional structures, either experimentally or by prediction, provides a powerful tool to address function, since it is at this level that biological activity is expressed. Here, we discuss the current approaches to protein structure prediction from sequence data, including the ab initio prediction of new folds, methods of fold recognition and comparative modelling based on homology. The value and limitations of such models are also explored. A major factor for the future will be the growth of the database of experimentally determined protein structures, through structural genomics projects. The prospects for this approach are also discussed, together with our experience in a pilot structural genomics project focused on proteins from Mycobacterium tuberculosis, the cause of tuberculosis (TB).

Computer Simulation↗
PubMed1998

The new paradigm: integrating genomic function and nuclear architecture.

A new view of the cell nucleus is emerging based on the functional dynamics of nuclear architecture. The striking structural preservation of a variety of genomic processes on the nuclear matrix provides an important approach for correlating nuclear form and function. In situ labeling coupled with three-dimensional microscopy and computer imaging techniques shows that DNA replication and transcription sites are organized into higher-order units, or "zones," in the cell nucleus. The dynamic interplay and "re-zoning" of replication and transcription regions during the cell cycle may form the structural basis for the elaborate global coordination of replicational and transcriptional programs in the mammalian cell.

Animals↗
PubMed2003

Highly efficient production and characterization of T-DNA plants for rice ( Oryza sativa L.) functional genomics.

We investigated the potential of an improved Agrobacterium tumefaciens-mediated transformation procedure of japonica rice ( Oryza sativa L.) for generating large numbers of T-DNA plants that are required for functional analysis of this model genome. Using a T-DNA construct bearing the hygromycin resistance ( hpt), green fluorescent protein ( gfp) and beta-glucuronidase ( gusA) genes, each individually driven by a CaMV 35S promoter, we established a highly efficient seed-embryo callus transformation procedure that results both in a high frequency (75-95%) of co-cultured calli yielding resistant cell lines and the generation of multiple (10 to more than 20) resistant cell lines per co-cultured callus. Efficiencies ranged from four to ten independent transformants per co-cultivated callus in various japonica cultivars. We further analysed the T-DNA integration patterns within a population of more than 200 transgenic plants. In the three cultivars studied, 30-40% of the T(0) plants were found to have integrated a single T-DNA copy. Analyses of segregation for hygromycin resistance in T(1) progenies showed that 30-50% of the lines harbouring multiple T-DNA insertions exhibited hpt gene silencing, whereas only 10% of lines harbouring a single T-DNA insertion was prone to silencing. Most of the lines silenced for hpt also exhibited apparent silencing of the gus and gfp genes borne by the T-DNA. The genomic regions flanking the left border of T-DNA insertion points were recovered in 477 plants and sequenced. Adapter-ligation Polymerase chain reaction analysis proved to be an efficient and reliable method to identify these sequences. By homology search, 77 T-DNA insertion sites were localized on BAC/PAC rice Nipponbare sequences. The influence of the organization of T-DNA integration on subsequent identification of T-DNA insertion sites and gene expression detection systems is discussed.

Agrobacterium tumefaciens↗