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Results for “Functional Genomics”

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At least 163 records · Page 9Linked to original sources
PubMed2005

A rapid and efficient method for purifying high quality total RNA from peaches (Prunus persica) for functional genomics analyses.

Prunus persica has been proposed as a genomic model for deciduous trees and the Rosaceae family. Optimized protocols for RNA isolation are necessary to further advance studies in this model species such that functional genomics analyses may be performed. Here we present an optimized protocol to rapidly and efficiently purify high quality total RNA from peach fruits (Prunus persica). Isolating high-quality RNA from fruit tissue is often difficult due to large quantities of polysaccharides and polyphenolic compounds that accumulate in this tissue and co-purify with the RNA. Here we demonstrate that a modified version of the method used to isolate RNA from pine trees and the woody plant Cinnamomun tenuipilum is ideal for isolating high quality RNA from the fruits of Prunus persica. This RNA may be used for many functional genomic based experiments such as RT-PCR and the construction of large-insert cDNA libraries.

DNA, Complementary↗
PubMed2005

Functional genomic analysis of the rates of protein evolution.

The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional genomic data sets yield three main results. First, dispensability and expression have independent, significant effects on the rate of protein evolution. Second, measurements of expression levels in the laboratory can be used to filter data sets of dispensability estimates, removing variates that are unlikely to reflect real biological effects. Third, structural equation models show that although we may reasonably infer that dispensability and expression have significant effects on protein evolutionary rate, we cannot yet accurately estimate the relative strengths of these effects.

Evolution, Molecular↗
PubMed2025

Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.

A small percentage of species in the fungal kingdom can cause devastating infections in humans, with Candida albicans reigning as a leading cause of systemic disease. One of the key virulence phenotypes for pathogenic fungi is the ability to survive at host body temperature; however, a comprehensive understanding of the mechanisms that orchestrate thermal adaptation in fungi remains incomplete. In this study, we expand the largest functional genomics resource in C. albicans, reaching 71.3% coverage of the entire genome, and perform screens under six different temperatures to identify genes important for temperature-dependent fitness. We describe the function of genes involved in translation (GAR1), splicing (C1_11680C or YSF3), and cell cycle progression (C6_00110C or RHT1) in enabling fungal survival at both low and high temperatures. Through experimental evolution, we also show that C. albicans can rapidly overcome deleterious mutations and adapt to extreme temperature environments. Overall, our study highlights the transformative potential of genome-wide functional genomics to uncover critical vulnerabilities in pathogenic fungi.

Genomics↗
PubMed2002

Odontogenic carcinoma: a functional genomic comparison with oral mucosal squamous cell carcinoma.

Intraosseous squamous cell carcinomas of the mandible arise de novo or secondary to a tumor or transformed cyst epithelium. Current diagnostic tests frequently fail to distinguish between these tumors, leading to confusing classification schemes. We report the functional genomic analysis of a mandibular odontogenic carcinoma. Malignant keratinocytes from the lesion were isolated using laser capture microdissection. Target sample generated from the total RNA of the LCM-procured cells was used to hybridize high-density oligonucleotide arrays. Functional genomic analysis of the odontogenic carcinoma database compared with four oral mucosal squamous cell carcinoma gene expression databases was performed. Preliminary results suggest a small subset of genes distinguish this odontogenic carcinoma from oral mucosal epidermoid carcinomas.

Carcinoma, Squamous Cell↗
PubMed2004

Functional genomics to new drug targets.

The completion of the sequencing of the human genome, and those of other organisms, is expected to lead to many potential new drug targets in various diseases, and it is predicted that novel therapeutic agents will be developed against such targets. The role of functional genomics in modern drug discovery is to prioritize these targets and to translate that knowledge into rational and reliable drug discovery. Here, we describe the field of functional genomics and review approaches that have been applied to drug discovery, including RNA profiling, proteomics, antisense and RNA interference, model organisms and high-throughput, genome-wide overexpression or knockdowns, and outline the future directions that are likely to yield new drug targets from genomics.

Animals↗
PubMed2004

A graph-theoretic approach to testing associations between disparate sources of functional genomics data.

MOTIVATION: The last few years have seen the advent of high-throughput technologies to analyze various properties of the transcriptome and proteome of several organisms. The congruency of these different data sources, or lack thereof, can shed light on the mechanisms that govern cellular function. A central challenge for bioinformatics research is to develop a unified framework for combining the multiple sources of functional genomics information and testing associations between them, thus obtaining a robust and integrated view of the underlying biology. RESULTS: We present a graph-theoretic approach to test the significance of the association between multiple disparate sources of functional genomics data by proposing two statistical tests, namely edge permutation and node label permutation tests. We demonstrate the use of the proposed tests by finding significant association between a Gene Ontology-derived predictome and data obtained from mRNA expression and phenotypic experiments for Saccharomyces cerevisiae. Moreover, we employ the graph-theoretic framework to recast a surprising discrepancy presented elsewhere between gene expression and knockout phenotype, using expression data from a different set of experiments. AVAILABILITY: An R software package, GraphAT, containing the data and statistical procedures is available from Bioconductor: http://www.bioconductor.org.

Algorithms↗
PubMed2002

Functional genomics approaches to understanding brain disorders.

The completed draft of the human genome sequence has facilitated a revolution in neuroscience research. This sequence information and the development of new technologies used to analyze gene expression on a genomic scale provides a new and powerful means to investigate brain disorders of unknown etiology and to isolate novel drug targets for these disorders. The term functional genomics broadly describes a set of technologies and strategies directed at the problem of determining the function of genes, and understanding how the genome works together to generate whole patterns of biological function. The most powerful of these functional genomics approaches, expression profiling or DNA microarrays, can be used to analyze the expression of thousands of genes simultaneously. The results to date from the application of DNA microarray methods to postmortem diseased human brain tissue, animal models and cell culture models of brain disorders provide an exciting glimpse into the future of this field.

Animals↗
PubMed2006

The ethics of functional genomics: same, same, but different?

Respect for human life--a notion of worth uniting all members of the human race--constitutes a sense of anthropocentrism that has long been the justification for the enrollment of animals in experimentation executed to develop therapies to alleviate human suffering. Currently, however, advances in functional genomics are causing a qualitative transformation of the rationale for medical research performed on animals. The notion of human distinctness is being fundamentally challenged when gene sequences similar to those found in humans are identified in different species. In this Opinion article, we would like to highlight an inherent tension brought about by the current developments in functional genomics: a tension between the scientific and the ethical status of gene sequences. Is it reasonable to argue that they are the same for all practical purposes but different in ethical status?

Animal Rights↗
PubMed2006

Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis.

BACKGROUND: Many model systems of human viral disease involve human-mouse chimeric tissue. One such system is the recently developed SCID-beige/Alb-uPA mouse model of hepatitis C virus (HCV) infection which involves a human-mouse chimeric liver. The use of functional genomics to study HCV infection in these chimeric tissues is complicated by the potential cross-hybridization of mouse mRNA on human oligonucleotide microarrays. To identify genes affected by mouse liver mRNA hybridization, mRNA from identical human liver samples labeled with either Cy3 or Cy5 was compared in the presence and absence of known amounts of mouse liver mRNA labeled in only one dye. RESULTS: The results indicate that hybridization of mouse mRNA to the corresponding human gene probe on Agilent Human 22 K oligonucleotide microarray does occur. The number of genes affected by such cross-hybridization was subsequently reduced to approximately 300 genes both by increasing the hybridization temperature and using liver samples which contain at least 80% human tissue. In addition, Real Time quantitative RT-PCR using human specific probes was shown to be a valid method to verify the expression level in human cells of known cross-hybridizing genes. CONCLUSION: The identification of genes affected by cross-hybridization of mouse liver RNA on human oligonucleotide microarrays makes it feasible to use functional genomics approaches to study the chimeric SCID-beige/Alb-uPA mouse model of HCV infection. This approach used to study cross-species hybridization on oligonucleotide microarrays can be adapted to other chimeric systems of viral disease to facilitate selective analysis of human gene expression.

Animals↗
PubMed2002

A functional genomics approach using metabolomics and in silico pathway analysis.

In the field of functional genomics increasing effort is being undertaken to analyze the function of orphan genes using metabolome data. Improved analytical equipment allows screening simultaneously for a high number of metabolites. Such metabolite profiles are analyzed using multivariate data analysis techniques and changes in the genotype will in many cases lead to different metabolite profiles. Here, a theoretical framework that may be applied to identify the function of orphan genes is presented. The approach is based on a combination of metabolome analysis combined with in silico pathway analysis. Pathway analysis may be carried out using convex analysis and a change in the active pathway structure of deletion mutants expressed in a different metabolite profile may disclose the function or the functional class of an orphan gene. The concept is illustrated using a simplified model for growth of Saccharomyces cerevisiae.

Algorithms↗
PubMed2006

Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics.

5,10-Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in the folate metabolic pathway. Common genetic polymorphisms in the human MTHFR gene are associated with individual variation in the efficacy and toxicity of chemotherapeutic agents, such as methotrexate and 5-fluorouracil. However, the full range of polymorphisms and intragene haplotypes in the human MTHFR gene remains unclear. Furthermore, cellular mechanisms by which common, naturally occurring nonsynonymous coding single nucleotide polymorphisms (cSNPs) might alter the function of this enzyme have not been defined. The present study focused on the systematic identification and investigation of common polymorphisms and haplotypes in the MTHFR gene using a genotype-to-phenotype strategy, followed by functional genomic studies. Specifically, we resequenced exons, splice junctions and portions of the 5'-flanking region (5'-FR) of the human MTHFR gene using 240 DNA samples from four ethnic groups. A total of 65 polymorphisms were observed, 11 of which were nonsynonymous cSNPs. We then performed functional genomic studies with constructs for wild-type and 15 variant allozymes (some with multiple alterations in amino acid sequence) using a mammalian expression system. Activity for the variant allozymes ranged from 13% to 149% of wild-type activity. Levels of immunoreactive protein for the allozymes ranged from 31% to 120% of wild-type and were significantly correlated with enzyme activity (Rp=0.85, P<0.0001), suggesting that a major mechanism by which nonsynonymous cSNPs influence the function of this gene is by alteration in the quantity of protein. These observations represent steps towards an understanding of molecular genetic mechanisms responsible for variation in MTHFR function that may contribute to individual differences in drug efficacy and toxicity, as well as disease risk.

5' Flanking Region↗
PubMed2002

Functional genomics: the coming of age for Tetrahymena thermophila.

Over the past decade, researchers have manipulated the unique biology of Tetrahymena thermophila to generate a premier experimental organism for functional genomic analysis. A diverse array of DNA transformation methods have spearheaded in vivo strategies for discovering and dissecting universal eukaryotic processes, such as telomere addition and chromatin remodeling. Compartmentalization of this protist's genome into two functionally distinct nuclei - the silent 'germline' micronucleus and the transcriptionally active macronucleus - provides a powerful means for controlling the expression of transgenes. Heterokaryons that silently harbor homozygous recessive mutations (including lethal ones) in the germline have been exploited. The coupling of forward and reverse genetic approaches with genomics-based methods for gene discovery presents a bright future for research in this rising model eukaryote.

Animals↗
PubMed2001

Http://C. elegans: mining the functional genomic landscape.

Caenorhabditis elegans is a powerful animal model for the study of functional genomics. The completed and well-annotated DNA sequence is available and a systematic study of gene function by RNA-interference-mediated knockdown of every gene is in progress. Full-genome DNA microarrays and DNA chips can be used to determine expression changes at different stages of development and in different mutant backgrounds, and a protein-interaction map based on the yeast two-hybrid approach is in progress. These high-capacity approaches to studying gene function will provide new insights into invertebrate and vertebrate biology.

Animals↗
PubMed2005

[From the mechanisms of genetic transposition to the functional genomics].

Pioneer works on studying molecular mechanisms of mutagenesis were published in the journal Genetika in the 1960s. In the laboratory of S.I. Alikhanian, studies on molecular mechanisms of genetic transposition were initiated in the late 1960s on the model of bacteriophage transposon Mu (Mutator). Parallel to these studies conducted in the laboratory of plant molecular genetics (Institute of Molecular Genetics, Academy of Sciences of the USSR), which was later named the Laboratory of Functional Genomics (Vavilov Institute of General Genetics, Russian Academy of Sciences), studies on transposition of Ti-plasmid T-DNA of Agrobacterium tumefaciens and works on construction of transgenic plants began in this laboratory. Transgenic plants with the expressed bacterial genes provided a model for the functional genomics. This topic is considered here in detail.

Animals↗
PubMed1998

Data transferability from model organisms to human beings: insights from the functional genomics of the flightless region of Drosophila.

At what biological levels are data from single-celled organisms akin to a Rosetta stone for multicellular ones? To examine this question, we characterized a saturation-mutagenized 67-kb region of the Drosophila genome by gene deletions, transgenic rescues, phenotypic dissections, genomic and cDNA sequencing, bio-informatic analysis, reverse transcription-PCR studies, and evolutionary comparisons. Data analysis using cDNA/genomic DNA alignments and bio-informatic algorithms revealed 12 different predicted proteins, most of which are absent from bacterial databases, half of which are absent from Saccharomyces cerevisiae, and nearly all of which have relatives in Caenorhabditis elegans and Homo sapiens. Gene order is not evolutionarily conserved; the closest relatives of these genes are scattered throughout the yeast, nematode, and human genomes. Most gene expression is pleiotropic, and deletion studies reveal that a morphological phenotype is seldom observed when these genes are removed from the genome. These data pinpoint some general bottlenecks in functional genomics, and they reveal the acute emerging difficulties with data transferability above the levels of genes and proteins, especially with complex human phenotypes. At these higher levels the Rosetta stone analogy has almost no applicability. However, newer transgenic technologies in Drosophila and Mus, combined with coherency pattern analyses of gene networks, and synthetic neural modeling, offer insights into organismal function. We conclude that industrially scaled robogenomics in model organisms will have great impact if it can be realistically linked to epigenetic analyses of human variation and to phenotypic analyses of human diseases in different genetic backgrounds.

Animals↗
PubMed2003

Evolutionary and ecological functional genomics.

A unique combination of disciplines is emerging--evolutionary and ecological functional genomics--which focuses on the genes that affect ecological success and evolutionary fitness in natural environments and populations. Already this approach has provided new insights that were not available from its disciplinary components in isolation. However, future advances will necessitate the re-engineering of scientific attitudes, training and institutions, to achieve extensive multidisciplinarity.

Animals↗
PubMed2006

Functional genome and proteome analyses of cutaneous autoimmune diseases.

The use of functional genomics and proteomics technologies has dramatically increased through recent years with a special emphasis on cancer biology. However, a series of more recent reports has also addressed inflammatory diseases. These included studies on different autoimmune diseases, such as rheumatoid arthritis, lupus erythematosus, and systemic sclerosis. Gene and protein expression profiles from these studies have emphasized the role of cytokines, chemokines, and apoptosis-related molecules for the pathogenesis of autoimmune diseases. Much less is known about gene and protein patterns of these diseases in dermatology. Here we provide an overview on current knowledge about genomics and proteomics analyses of cutaneous autoimmune diseases. These diseases include psoriasis, lupus erythematosus, systemic sclerosis, vitiligo, and alopecia areata. The presented findings not only provide deeper insights into the pathogenesis of each individual disease but also show overlapping gene patterns suggestive for common pathogenic mechanisms. However, many open questions remain to be resolved since data about local gene expression pattern in affected tissues are still scarce.

Animals↗