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 235 records · Page 13Linked to original sources
PubMed2002

Perspective: the ovarian kaleidoscope database-II. Functional genomic analysis of an organ-specific database.

In the postgenomic era, it is now possible to investigate the function of all human genes to provide an integrated view of physiology and pathophysiology. An organ-based approach has been used to set up a database integrating existing text-based literature on individual ovarian genes and their sequence-based data in the GenBank. The Ovarian Kaleidoscope database (OKdb) has accumulated nearly one thousand individual gene pages that are searchable based on gene function, cellular localization, chromosomal position, ovarian cell type, ovarian function, mutant phenotypes, and other criteria. The present review exemplifies the use of this organ-based database in setting up gene pathway maps for DNA array analysis, identifying key gene networks essential for infertility phenotypes, comparing chromosomal synteny regions for finding candidate fertility genes, categorizing cell-specific and hormonally coregulated genes for promoter analysis, and documenting potential ligands and receptors in the paracrine regulation of follicular development. The present global analysis of gene function and relationships in an organ-specific manner provides a functional genomic paradigm for the future understanding of the physiology and pathophysiology of diverse organs.

Animals↗
PubMed2005

Virus infection and the interferon response: a global view through functional genomics.

The primary focus of this chapter is on providing an overview of how we use the tools of functional genomics to study virus infection, the interferon response, and the mechanisms by which viruses attenuate or evade this response to ensure successful replication. We provide examples of the types of analyses we perform, experimental design considerations, and the tools and techniques we use for data processing and mining. We have not attempted to provide detailed protocols for performing microarray or proteomics experiments because even individual components of such analyses, for example, techniques for the isolation and amplification of ribonucleic acid, could easily be the subject of an entire chapter. Rather, our goal is to show how data obtained from global gene expression and protein profiling can be used to gain new insights into virus-host interactions, with particular emphasis on the interferon response and its modulation by virus infection.

Animals↗
PubMed2006

Functional genomic approaches in C. elegans.

The nematode Caenorhabditis elegans is an extraordinarily powerful model organism for the application of functional genomic approaches. Two such approaches, whole genome microarray analysis and genome-wide RNA interference (RNAi)-mediated phenotypic screening, are highly advanced and can be used by virtually any laboratory to study biological processes of interest. Using studies of the osmotic stress response in C. elegans as an example, this chapter describes methods for conducting whole genome microarray experiments and for carrying out genome-wide reverse-genetic screens using a commercially available C. elegans bacterial RNAi feeding library. Both approaches are complimentary and can be used to rapidly gain genome-wide insights into the genes and gene networks controlling specific physiological processes.

Animals↗
PubMed2006

Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents.

Recent advances in functional genomics afford the opportunity to interrogate the expression profiles of thousands of genes simultaneously and examine the function of these genes in a high-throughput manner. In this study, we describe a rational and efficient approach to identifying novel regulators of insulin secretion by the pancreatic beta-cell. Computational analysis of expression profiles of several mouse and cellular models of impaired insulin secretion identified 373 candidate genes involved in regulation of insulin secretion. Using RNA interference, we assessed the requirements of 10 of these candidates and identified four genes (40%) as being essential for normal insulin secretion. Among the genes identified was Hadhsc, which encodes short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD), an enzyme of mitochondrial beta-oxidation of fatty acids whose mutation results in congenital hyperinsulinism. RNA interference-mediated gene suppression of Hadhsc in insulinoma cells and primary rodent islets revealed enhanced basal but normal glucose-stimulated insulin secretion. This increase in basal insulin secretion was not attenuated by the opening of the KATP channel with diazoxide, suggesting that SCHAD regulates insulin secretion through a KATP channel-independent mechanism. Our results suggest a molecular explanation for the hyperinsulinemia hypoglycemic seen in patients with SCHAD deficiency.

Animals↗
PubMed2003

Integrating proteomic and functional genomic technologies in discovery-driven translational breast cancer research.

The application of state-of-the-art proteomics and functional genomics technologies to the study of cancer is rapidly shifting toward the analysis of clinically relevant samples derived from patients, as the ultimate aim of translational research is to bring basic discoveries closer to the bedside. Here we describe the essence of a long-term initiative undertaken by The Danish Centre for Translational Breast Cancer Research and currently underway for cancer biomarker discovery using fresh tissue biopsies and bio-fluids. The Centre is a virtual hub that brings together scientists working in various areas of basic cancer research such as cell cycle control, invasion and micro-environmental alterations, apoptosis, cell signaling, and immunology, with clinicians (oncologists, surgeons), pathologists, and epidemiologists, with the aim of understanding the molecular mechanisms underlying breast cancer progression and ultimately of improving patient survival and quality of life. The unifying concept behind our approach is the use of various experimental paradigms for the prospective analysis of clinically relevant samples obtained from the same patient, along with the systematic integration of the biological and clinical data.

Academies and Institutes↗
PubMed2006

From information to understanding: the role of model organism databases in comparative and functional genomics.

Data integration is key to functional and comparative genomics because integration allows diverse data types to be evaluated in new contexts. To achieve data integration in a scalable and sensible way, semantic standards are needed, both for naming things (standardized nomenclatures, use of key words) and also for knowledge representation. The Mouse Genome Informatics database and other model organism databases help to close the gap between information and understanding of biological processes because these resources enforce well-defined nomenclature and knowledge representation standards. Model organism databases have a critical role to play in ensuring that diverse kinds of data, especially genome-scale data sets and information, remain useful to the biological community in the long-term. The efforts of model organism database groups ensure not only that organism-specific data are integrated, curated and accessible but also that the information is structured in such a way that comparison of biological knowledge across model organisms is facilitated.

Animals↗
PubMed2001

Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism.

This review focuses on the functional genomics of the human paraoxonase (PON1) polymorphisms. Levels and genetic variability of the PON1 position 192 isoforms (Gln/Arg) influence sensitivity to specific insecticides or nerve agents and risk for cardiovascular disease. A more recent area of investigation, the role of PON1 in drug metabolism, is also discussed. We emphasize the importance of considering both PON1 isoforms and PON1 levels in disease/sensitivity association studies.

Animals↗
PubMed2001

Functional genomics in the study of seed germination.

A recent proteomic analysis of germinating Arabidopsis thaliana seeds demonstrates the effectiveness of functional genomics for investigating the complexity of developmental regulatory networks, such as the development of the embryo into a young plant.

Arabidopsis↗
PubMed2003

Cerebral chemical dominance and neural regulation of cell division, cell proliferation, neoplastic transformation, and genomic function.

The study assessed the isoprenoid pathway, digoxin synthesis, and neurotransmitter patterns in individuals of differing hemispheric dominance, neurogenetic disorders, and neoplasms. The HMG CoA reductase activity, serum digoxin, magnesium, tryptophan catabolites, tyrosine catabolites, and RBC membrane Na+-K+ ATPase activity were measured in individuals of differing hemispheric dominance. The digoxin status, membrane Na+-K+ ATPase activity, and serum magnesium were assessed in Huntington's disease, trisomy 21, glioblastoma multiforme, and non-Hodgkin's lymphoma (high grade lymphoma). The results showed that right hemispheric, chemically dominant individuals had elevated digoxin synthesis, increased tryptophan catabolites, and reduced tyrosine catabolites, and membrane Na+-K+ ATPase with hypomagnesemia. Left hemispheric, chemically dominant individuals had the opposite patterns. In neurogenetic disorders and neo plasms also hyperdigoxinemia induced membrane Na+-K+ ATPase inhibition, and hypomagnesemia similar to right hemispheric chemical dominance could be demonstrated. The role of hemispheric chemical dominance and hypothalamic digoxin secretion play a key role in the regulation of cell differentiation/proliferation and genomic function. Ninety-five percent of the patients with neurogenetic disorders and neoplasms were right-handed/left hemispheric dominant by dichotic listening test. However, all of them had biochemical patterns similar to right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation to cerebral dominance detected by handness/dichotic listening test.

Adult↗
PubMed2000

Genome sequence comparisons: hurdles in the fast lane to functional genomics.

An important computational technique for extracting the wealth of information hidden in human genomic sequence data is to compare the sequence with that from the corresponding region of the mouse genome, looking for segments that are conserved over evolutionary time. Moreover, the approach generalises to comparison of sequences from any two related species. The underlying rationale (which is abundantly confirmed by observation) is that a random mutation in a functional region is usually deleterious to the organism, and hence unlikely to become fixed in the population, whereas mutations in a non-functional region are free to accumulate over time. The potential value of this approach is so attractive that the public and private projects to sequence the human genome are now turning to sequencing the mouse, and you will soon be able to compare the human and mouse sequences of your favourite genomic region. We are currently witnessing an explosion of computer tools for comparative analysis of two genomic sequences. Here the capabilities of two new network servers for comparing genomic sequences from any pair of closely related species are sketched. The Syntenic Gene Prediction Program SGP-I utilises sequence comparisons to enhance the ability to locate protein coding segments in genomic data. PipMaker attempts to determine all conserved genomic regions, regardless of their function.

Animals↗
PubMed2002

A 3800 gene microarray for cattle functional genomics: comparison of gene expression in spleen, placenta, and brain.

A cDNA microarray representing approximately 3800 cattle genes was created for functional genomic studies. The array elements were selected from > 7000 cDNA clones identified in a large-scale expressed sequence tag (EST) project that utilized spleen and normalized and subtracted placenta cDNA libraries. Sequence similarity searches of the 3820 ESTs represented on the array using BLASTN identified 3290 (86.1%) as putative human orthologs, with the remainder consisting of "novel" genes or highly divergent orthologs. Experiments were conducted with a prototype 768 gene microarray created from spleen cDNAs and with the 3800 gene array that included genes from spleen and placenta. The 768 gene array was used to profile RNA transcripts expressed by adult and fetal spleen. The 3800 gene array was used to profile transcripts expressed by adult brain and placenta. Microarray analysis of RNA extracted from fetal and adult spleen identified 29 genes that were differentially expressed two-fold or more. Transcriptional differences of two of these genes, IGJ and CTSS, were confirmed using TaqMan technology. The comparison of brain and placenta revealed 400 genes expressed at higher levels in brain and 72 genes expressed at higher levels in placenta. These results demonstrate the potential power of microarrays for understanding the molecular mechanisms of cattle development, disease resistance, nutrition, fertility and production traits.

Animals↗
PubMed2000

Current awareness on comparative and functional genomics [bibliography].

In order to keep subscribers up-to-date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly-published material on comparative and functional genomics. Each bibliography is divided into 16 sections. 1 Reviews & symposia; 2 General; 3 Large-scale sequencing and mapping; 4 Genome evolution; 5 Comparative genomics; 6 Gene families and regulons; 7 Pharmacogenomics; 8 Large-scale mutagenesis programmes; 9 Functional complementation; 10 Transcriptomics; 11 Proteomics; 12 Protein structural genomics; 13 Metabolomics; 14 Genomic approaches to development; 15 Technological advances; 16 Bioinformatics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

Animals↗
PubMed2005

Functional genomics of the regulation of the nitrate assimilation pathway in Chlamydomonas.

The existence of mutants at specific steps in a pathway is a valuable tool of functional genomics in an organism. Heterologous integration occurring during transformation with a selectable marker in Chlamydomonas (Chlamydomonas reinhardtii) has been used to generate an ordered mutant library. A strain, having a chimeric construct (pNia1::arylsulfatase gene) as a sensor of the Nia1 gene promoter activity, was transformed with a plasmid bearing the paramomycin resistance AphVIII gene to generate insertional mutants defective at regulatory steps of the nitrate assimilation pathway. Twenty-two thousand transformants were obtained and maintained in pools of 96 for further use. The mutant library was screened for the following phenotypes: insensitivity to the negative signal of ammonium, insensitivity to the positive signal of nitrate, overexpression in nitrate, and inability to use nitrate. Analyses of mutants showed that (1) the number or integrated copies of the gene marker is close to 1; (2) the probability of cloning the DNA region at the marker insertion site is high (76%); (3) insertions occur randomly; and (4) integrations at different positions and orientations of the same genomic region appeared in at least three cases. Some of the mutants analyzed were found to be affected at putative new genes related to regulatory functions, such as guanylate cyclase, protein kinase, peptidyl-prolyl isomerase, or DNA binding. The Chlamydomonas mutant library constructed would also be valuable to identify any other gene with a screenable phenotype.

Ammonia↗
PubMed2004

Virus-induced gene silencing as a tool for functional genomics in a legume species.

Virus-induced gene silencing (VIGS) is an attractive reverse-genetics tool for studies of gene function. However, efficient VIGS has only been accomplished in a few plant species. In order to extend the application of VIGS, we examined whether a VIGS vector based on Pea early browning virus (PEBV) would produce recognizable phenotypes in Pisum sativum. A plasmid vector of PEBV was modified to allow agro-inoculation and insertion of heterologous sequences. cDNA fragments of the P. sativum phytoene desaturase (PDS), LEAFY (LFY) and KORRIGAN1 (KOR1) homologues were inserted into the PEBV RNA2 vector, replacing the genes required for nematode transmission. Pisum sativum inoculated with PEBV carrying a fragment of PsPDS developed characteristic photo-bleached leaves and this phenotype was associated with a significant reduction in PsPDS mRNA. The P. sativum homologue of LFY is known as UNIFOLIATA (UNI). Plants inoculated with PEBV carrying a fragment of UNI developed distorted flowers and leaves with modified architecture, which are also observed in UNI-mutants. In Arabidopsis thaliana, the KOR1-mutant is characterized by an extreme dwarf phenotype. Pisum sativum plants inoculated with PEBV carrying a fragment of PsKOR1 displayed a significant reduction in height and inhibition of root growth. The PEBV VIGS vector did not affect the ability of P. sativum to flower, set seeds, and form nodules characteristic of symbiosis with rhizobium. These results suggest that the PEBV vector can be applied to functional genomics in a legume species to study genes involved in a wide range of biological processes.

Gene Expression Regulation, Plant↗
PubMed2021

Towards a CRISPeR understanding of homologous recombination with high-throughput functional genomics.

CRISPR-dependent genome editing enables the study of genes and mutations on a large scale. Here we review CRISPR-based functional genomics technologies that generate gene knockouts and single nucleotide variants (SNVs) and discuss how their use has provided new important insights into the function of homologous recombination (HR) genes. In particular, we highlight discoveries from CRISPR screens that have contributed to define the response to PARP inhibition in cells deficient for the HR genes BRCA1 and BRCA2, uncover genes whose loss causes synthetic lethality in combination with BRCA1/2 deficiency, and characterize the function of BRCA1/2 SNVs of uncertain clinical significance. Further use of these approaches, combined with next-generation CRISPR-based technologies, will aid to dissect the genetic network of the HR pathway, define the impact of HR mutations on cancer etiology and treatment, and develop novel targeted therapies for HR-deficient tumors.

Gene Regulatory Networks↗
PubMed2003

The pain of antisense: in vivo application of antisense oligonucleotides for functional genomics in pain and analgesia.

As the genomic revolution continues to evolve, there is an increasing demand for efficient and reliable tools for functional characterization of individual gene products. Antisense oligonucleotide-mediated knockdown has been used successfully as a functional genomics tool in animal models of pain and analgesia yet skepticism regarding the validity and utility of antisense technology remains. Contributing to this uncertainty are the lack of systematic studies exploring antisense oligonucleotide use in vivo and the many technical and methodological challenges intrinsic to the method. This article reviews the contributions of antisense oligonucleotide-based studies to the field of pain and analgesia and the general principles of antisense technology. A special emphasis is placed on technical issues surrounding the successful application of antisense oligonucleotides in vivo, including sequence selection, antisense oligonucleotide chemistry, DNA controls, route of administration, uptake, dose-dependence, time-course and adequate evaluation of knockdown.

Analgesia↗
PubMed2002

Unlocking the mysteries of virus-host interactions: does functional genomics hold the key?

The interactions between viruses and the cells they infect are complex and multifaceted. While viruses strive to usurp cellular functions to their advantage, the cell strives to thwart these efforts by mounting a variety of defensive responses. These responses may include the induction of interferon, stress response, or apoptotic pathways, all of which are accompanied by changes in gene expression. Some viruses consistently win this tug of war, whereas others succumb to cellular defense mechanisms. The viral and cellular factors that determine the outcome are for the most part still unknown. With the advent of functional genomics, potent new technologies are now available to probe the complexities of virus-host interactions in ever increasing depth and detail. We describe here our efforts to use microarrays, proteomics, and bioinformatics to focus in on the changes in gene expression and protein production that occur in a virus-infected cell and to use these technologies to unlock the mysteries of virus-host interactions.

Animals↗
PubMed2026

Spatially guided in vivo single-cell functional genomics of postnatal heart.

Understanding how spatial organization and cell-cell interactions shape gene regulatory programs is central to decoding tissue development and function. The transition at birth, marked by increased circulatory demands and rapid tissue growth, requires precise spatiotemporal coordination of cardiac maturation. In this study, we generated a high-resolution spatial and temporal atlas of the postnatal mouse heart by integrating single-nucleus RNA sequencing with image-based spatial transcriptomics. This framework revealed dynamic cellular interactions, niche-specific signaling and transcriptional programs guiding cardiomyocyte maturation. To functionally test prioritized regulators in vivo and at scale, we developed PIP-seq (probe-based indel-detectable Perturb-seq), a high-throughput platform that detects single guide RNA identity, infers gene editing and profiles transcription from fixed nuclei. Applying PIP-seq to the developing postnatal heart, we identified 21 previously uncharacterized regulators of cardiomyocyte maturation, including genes essential for sarcomere assembly, metabolic reprogramming and electrophysiological transitions. Together, our findings define how microenvironmental signals and intrinsic gene programs cooperate to guide heart maturation and establish a broadly applicable framework for functional genomics in complex tissues.

Animals↗