Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genome mining”

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 307 records · Page 17Linked to original sources
PubMed2006

Survey of microarray technologies suitable to elucidate transcriptional networks as exemplified by studying KRAB zinc finger gene families.

Current microarray systems are suitable to monitor genome-wide expression patterns, to detect single-nucleotide polymorphisms (SNP), to identify target genes of transcription factors and DNA-protein interaction sites thereof as well as to determine genomic sites that are modified by methylation of CpG islands. In this review, advantages and limitations of individual microarray technologies are presented as well as experiences from ongoing studies on KRAB zinc finger gene families are taken to exemplify how different microarray approaches are applicable to elucidate complex transcriptional networks of gene regulation. However, bioinformaticians should be aware that each microarray technology has limitations in its sensitivity and selectivity that has to be taken into account once data mining on comprehensive genome-wide microarray data is conducted. In many cases, microarray results are the initial step to identify target genes of interest and to study the molecular regulation of biological processes thereof followed and validated by complementary proteome, metabolome or toponome analysis. Thus, microarray technologies can be considered a reliable approach for determining gene functions that might be modulated by electromagnetic fields.

Gene Expression Profiling↗
PubMed2006

Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

Animals↗
PubMed2002

Psychiatric genetics in silico: databases and tools for psychiatric geneticists.

Bioinformatics can significantly impact the laboratory genetics process from the study design phase to conclusive identification of a disease gene. The present review will highlight key databases to enhance psychiatric genetic study design, based on full use of genomics data and the golden path sequence. It will address methods to ensure comprehensive genetic data mining, using the best available genomic and genetic databases such as the University of California Santa Cruz human genome browser, Ensembl, Mapview, dbSNP and GDB, and locus-specific databases such as Online Mendelian Inheritance In Man. Using the golden path sequence as a template, with the necessary quality checks, it is possible to design detailed genetic studies from sequence information alone. Drawing together this diverse information, it is possible to characterize a locus or gene in silico to a very detailed level. This in turn can have real cost and efficiency benefits by assisting in the identification of markers that are most likely to be informative, or by highlighting the best candidate genes for study.

Databases, Bibliographic↗
PubMed2003

Whole-proteome interaction mining.

MOTIVATION: A major post-genomic scientific and technological pursuit is to describe the functions performed by the proteins encoded by the genome. One strategy is to first identify the protein-protein interactions in a proteome, then determine pathways and overall structure relating these interactions, and finally to statistically infer functional roles of individual proteins. Although huge amounts of genomic data are at hand, current experimental protein interaction assays must overcome technical problems to scale-up for high-throughput analysis. In the meantime, bioinformatics approaches may help bridge the information gap required for inference of protein function. In this paper, a previously described data mining approach to prediction of protein-protein interactions (Bock and Gough, 2001, Bioinformatics, 17, 455-460) is extended to interaction mining on a proteome-wide scale. An algorithm (the phylogenetic bootstrap) is introduced, which suggests traversal of a phenogram, interleaving rounds of computation and experiment, to develop a knowledge base of protein interactions in genetically-similar organisms. RESULTS: The interaction mining approach was demonstrated by building a learning system based on 1,039 experimentally validated protein-protein interactions in the human gastric bacterium Helicobacter pylori. An estimate of the generalization performance of the classifier was derived from 10-fold cross-validation, which indicated expected upper bounds on precision of 80% and sensitivity of 69% when applied to related organisms. One such organism is the enteric pathogen Campylobacter jejuni, in which comprehensive machine learning prediction of all possible pairwise protein-protein interactions was performed. The resulting network of interactions shares an average protein connectivity characteristic in common with previous investigations reported in the literature, offering strong evidence supporting the biological feasibility of the hypothesized map. For inferences about complete proteomes in which the number of pairwise non-interactions is expected to be much larger than the number of actual interactions, we anticipate that the sensitivity will remain the same but precision may decrease. We present specific biological examples of two subnetworks of protein-protein interactions in C. jejuni resulting from the application of this approach, including elements of a two-component signal transduction systems for thermoregulation, and a ferritin uptake network.

Algorithms↗
PubMed2004

Evidence that CTR1-mediated ethylene signal transduction in tomato is encoded by a multigene family whose members display distinct regulatory features.

Ethylene governs a range of developmental and response processes in plants. In Arabidopsis thaliana, the Raf-like kinase CTR1 acts as a key negative regulator of ethylene responses. While only one gene with CTR1 function apparently exists in Arabidopsis, we have isolated a family of CTR1- like genes in tomato ( Lycopersicon esculentum ). Based on amino acid alignments and phylogenetic analysis, these tomato CTR1- like genes are more similar to Arabidopsis CTR1 than any other sequences in the Arabidopsis genome. Structural analysis reveals considerable conservation in the size and position of the exons between Arabidopsis and tomato CTR1 genomic sequences. Complementation of the Arabidopsis ctr1-8 mutant with each of the tomato CTR genes indicates that they are all capable of functioning as negative regulators of the ethylene pathway. We previously reported that LeCTR1 expression is up-regulated in response to ethylene. Here, quantitative real-time PCR was carried out to detail expression for LeCTR1 and the additional CTR1 -like genes of tomato. Our results indicate that the tomato CTR1 gene family is differentially regulated at the mRNA level by ethylene and during stages of development marked by increased ethylene biosynthesis, including fruit ripening. The possibility of a multi-gene family of CTR1 -like genes in other species besides tomato was examined through mining of EST and genomic sequence databases.

Amino Acid Sequence↗
PubMed2005

DNA-binding specificity of rice mariner-like transposases and interactions with Stowaway MITEs.

Mariner-like elements (MLEs) are DNA transposons found throughout the plant and animal kingdoms. A previous computational survey of the rice (Oryza sativa) genome sequence revealed 34 full length MLEs (Osmars) belonging to 25 distinct families. This survey, which also identified sequence similarities between the Osmar elements and the Stowaway superfamily of MITEs, led to the formulation of a hypothesis whereby Stowaways are mobilized by OSMAR transposases. Here we investigate the DNA-binding activities and specificities of two OSMAR transposases, OSMAR5 and OSMAR10. Like other mariner-like transposases, the OSMARs bind specifically to the terminal inverted repeat (TIR) sequences of their encoding transposons. OSMAR5 binds DNA through a bipartite N-terminal domain containing two functionally separable helix-turn-helix motifs, resembling the paired domain of Tc1-like transposases and PAX transcription factors in metazoans. Furthermore, binding of the OSMARs is not limited to their own TIRs; OSMAR5 transposase can also interact in vitro with TIRs from closely related Osmar elements and with consensus TIRs of several Stowaway families mined from the rice genome sequence. These results provide the first biochemical evidence for a functional relationship between Osmar elements and Stowaway MITEs and lead us to suggest that there is extensive cross-talk among related but distinct transposon families co-existing in a single eukaryote genome.

Base Sequence↗
PubMed2003

Expression profiling and bioinformatic analyses of a novel stress-regulated multispanning transmembrane protein family from cereals and Arabidopsis.

Cold acclimation is a multigenic trait that allows hardy plants to develop efficient tolerance mechanisms needed for winter survival. To determine the genetic nature of these mechanisms, several cold-responsive genes of unknown function were identified from cold-acclimated wheat (Triticum aestivum). To identify the putative functions and structural features of these new genes, integrated genomic approaches of data mining, expression profiling, and bioinformatic predictions were used. The analyses revealed that one of these genes is a member of a small family that encodes two distinct groups of multispanning transmembrane proteins. The cold-regulated (COR)413-plasma membrane and COR413-thylakoid membrane groups are potentially targeted to the plasma membrane and thylakoid membrane, respectively. Further sequence analysis of the two groups from different plant species revealed the presence of a highly conserved phosphorylation site and a glycosylphosphatidylinositol-anchoring site at the C-terminal end. No homologous sequences were found in other organisms suggesting that this family is specific to the plant kingdom. Intraspecies and interspecies comparative gene expression profiling shows that the expression of this gene family is correlated with the development of freezing tolerance in cereals and Arabidopsis. In addition, several members of the family are regulated by water stress, light, and abscisic acid. Structure predictions and comparative genome analyses allow us to propose that the cor413 genes encode putative G-protein-coupled receptors.

Acclimatization↗
PubMed2005

ASAP: amplification, sequencing & annotation of plastomes.

BACKGROUND: Availability of DNA sequence information is vital for pursuing structural, functional and comparative genomics studies in plastids. Traditionally, the first step in mining the valuable information within a chloroplast genome requires sequencing a chloroplast plasmid library or BAC clones. These activities involve complicated preparatory procedures like chloroplast DNA isolation or identification of the appropriate BAC clones to be sequenced. Rolling circle amplification (RCA) is being used currently to amplify the chloroplast genome from purified chloroplast DNA and the resulting products are sheared and cloned prior to sequencing. Herein we present a universal high-throughput, rapid PCR-based technique to amplify, sequence and assemble plastid genome sequence from diverse species in a short time and at reasonable cost from total plant DNA, using the large inverted repeat region from strawberry and peach as proof of concept. The method exploits the highly conserved coding regions or intergenic regions of plastid genes. Using an informatics approach, chloroplast DNA sequence information from 5 available eudicot plastomes was aligned to identify the most conserved regions. Cognate primer pairs were then designed to generate approximately 1 - 1.2 kb overlapping amplicons from the inverted repeat region in 14 diverse genera. RESULTS: 100% coverage of the inverted repeat region was obtained from Arabidopsis, tobacco, orange, strawberry, peach, lettuce, tomato and Amaranthus. Over 80% coverage was obtained from distant species, including Ginkgo, loblolly pine and Equisetum. Sequence from the inverted repeat region of strawberry and peach plastome was obtained, annotated and analyzed. Additionally, a polymorphic region identified from gel electrophoresis was sequenced from tomato and Amaranthus. Sequence analysis revealed large deletions in these species relative to tobacco plastome thus exhibiting the utility of this method for structural and comparative genomics studies. CONCLUSION: This simple, inexpensive method now allows immediate access to plastid sequence, increasing experimental throughput and serving generally as a universal platform for plastid genome characterization. The method applies well to whole genome studies and speeds assessment of variability across species, making it a useful tool in plastid structural genomics.

Base Sequence↗
PubMed2006

The TREC 2004 genomics track categorization task: classifying full text biomedical documents.

BACKGROUND: The TREC 2004 Genomics Track focused on applying information retrieval and text mining techniques to improve the use of genomic information in biomedicine. The Genomics Track consisted of two main tasks, ad hoc retrieval and document categorization. In this paper, we describe the categorization task, which focused on the classification of full-text documents, simulating the task of curators of the Mouse Genome Informatics (MGI) system and consisting of three subtasks. One subtask of the categorization task required the triage of articles likely to have experimental evidence warranting the assignment of GO terms, while the other two subtasks were concerned with the assignment of the three top-level GO categories to each paper containing evidence for these categories. RESULTS: The track had 33 participating groups. The mean and maximum utility measure for the triage subtask was 0.3303, with a top score of 0.6512. No system was able to substantially improve results over simply using the MeSH term Mice. Analysis of significant feature overlap between the training and test sets was found to be less than expected. Sample coverage of GO terms assigned to papers in the collection was very sparse. Determining papers containing GO term evidence will likely need to be treated as separate tasks for each concept represented in GO, and therefore require much denser sampling than was available in the data sets. The annotation subtask had a mean F-measure of 0.3824, with a top score of 0.5611. The mean F-measure for the annotation plus evidence codes subtask was 0.3676, with a top score of 0.4224. Gene name recognition was found to be of benefit for this task. CONCLUSION: Automated classification of documents for GO annotation is a challenging task, as was the automated extraction of GO code hierarchies and evidence codes. However, automating these tasks would provide substantial benefit to biomedical curation, and therefore work in this area must continue. Additional experience will allow comparison and further analysis about which algorithmic features are most useful in biomedical document classification, and better understanding of the task characteristics that make automated classification feasible and useful for biomedical document curation. The TREC Genomics Track will be continuing in 2005 focusing on a wider range of triage tasks and improving results from 2004.

Journal Article↗
PubMed2001

Computational method to assign microbial genes to pathways.

We present techniques that mine fully sequenced microbial genomes for functional relationships between genes. We show that genes related by one of four techniques are more likely to belong to the same cellular pathways. Furthermore, we demonstrate that the pathway of an uncharacterized gene may be inferred from those of its functionally related partners. Therefore, we are now able to assign most of the genes within bacteria to cellular pathways.

Computational Biology↗
PubMed2004

How bioinformatics can help reverse engineer human aging.

To study human aging is an enormous challenge. The complexity of the aging phenotype and the near impossibility of studying aging directly in humans oblige researchers to resort to models and extrapolations. Computational approaches offer a powerful set of tools to study human aging. In one direction we have data-mining methods, from comparative genomics to DNA microarrays, to retrieve information in large amounts of data. Afterwards, tools from systems biology to reverse engineering algorithms allow researchers to integrate different types of information to increase our knowledge about human aging. Computer methodologies will play a crucial role to reconstruct the genetic network of human aging and the associated regulatory mechanisms.

Aging↗
PubMed2004

Plant protein inhibitors of invertases.

In higher plants, cell wall (CWI) and vacuolar invertases (VI) are important metabolic enzymes, but are also key players during wound and pathogen defense reactions and in several developmental transitions. These multiple functions are implemented by small gene families. While induction of CWI and VI activities usually operates via increased transcription of the corresponding isoform gene, the equally important silencing of invertase activity depends on post-translational mechanisms, including inactivation by specific inhibitor proteins. Recently, the first cDNAs for plant invertase inhibitors were cloned, NtCIF and NtVIF (cell wall/vacuolar inhibitor of beta-fructosidase). The encoded proteins have been expressed in E. coli for functional studies and transgenic tobacco and potato plants were generated to explore the inhibitor function(s) in vivo. Mining the Arabidopsis thaliana genome revealed an inhibitor protein family of limited sequence conservation, some members grouping with tobacco CIF and VIF, while others showing a closer similarity with a recently identified inhibitor of pectin methylesterase. In vitro studies have confirmed target enzyme specificity for invertase and pectin methylesterase inhibitors (PMEI), respectively. The current status of research on invertase inhibitors and the perspectives for their use in plant biotechnology will be discussed.

Abscisic Acid↗
PubMed2003

A comprehensive search for HNF-3alpha-regulated genes in mouse hepatoma cells by 60K cDNA microarray and chromatin immunoprecipitation/PCR analysis.

To characterize the regulatory pattern by a specific transcription regulatory factor, we used a combination of expression analysis with the mouse cDNA microarray composed of 60,000 cDNA clones and cross-linking/chromatin immunoprecipitation (X-ChIP) followed by comparative PCR. Overexpression of mouse hepatocyte nuclear factor-3alpha (HNF-3alpha) in a mouse hepatoma cell line resulted in accompanied perturbed expression of more than 1500 genes. Search for HNF-3alpha consensus recognition sequences in the upstream regions of their coding sequences, which were mapped on the mouse genome, enabled us to mine 300 genes as the potential HNF-3alpha-regulated genes and classify 135 annotated ones into several functional categories. Further X-ChIP/PCR analysis demonstrated in vivo binding of HNF-3alpha to the 5(')-flanking sequences of 25 members selected out of these genes. Besides known HNF-3alpha-regulated genes such as albumin and alpha-fetoprotein genes, the genes newly identified as the HNF-3alpha-regulated ones include three encoding CDP-diacylglycerol-inositol 3-phosphatidyltransferase, phosphatidylserine decarboxylase, and phospholipase A2, which are located en suite in the lipid metabolic pathway in liver. The potential usefulness of the present approach to extensive characterization of gene expression framework directed by a specific transcription regulatory factor is discussed.

5' Flanking Region↗
PubMed2006

Substrate specificity of Arabidopsis 3-ketoacyl-CoA synthases.

The very long chain fatty acids (VLCFA) incorporated into plant lipids are derived from the iterative addition of C2 units provided by malonyl-CoA to an acyl-CoA by the 3-ketoacyl-CoA synthase (KCS) component of a fatty acid elongase (FAE) complex. Mining of the Arabidopsis genome sequence database revealed 20 genes with homology to seed-specific FAE1 KCS. Eight of the 20 putative KCSs were cloned, expressed in yeast, and isolated as (His)6 fusion proteins. Five of the eight (At1g71160, At1g19440, At1g07720, At5g04530, and At4g34250) had little or no activity with C16 to C20 substrates while three demonstrated activity with C16, C18, and C20 saturated acyl-CoA substrates. At1g01120 KCS (KCS1) and At2g26640 KCS had broad substrate specificities when assayed with saturated and mono-unsaturated C16 to C24 acyl-CoAs while At4g34510 KCS was specific for saturated fatty acyl-CoA substrates.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed2005

Manifestation, mechanisms and mysteries of gene amplifications.

Gene amplifications are essential features of advanced cancers and have prognostic as well as therapeutic significance in clinical cancer treatment. Models explaining the amplification process, such as breakage-fusion-bridge cycle and excision and unequal segregation of extrachromosomal DNA fragments, predict that independent DNA double-stranded breaks must occur to induce amplification formation. Many cellular, tissue and environmental factors induce DNA damage and amplifications. Also labile DNA sequence features like fragile sites facilitate amplifications. Although, databases and data mining tools of various genomic attributes are already available, extra-large scale systems biology endeavors to decipher dynamics, interactions and dependencies between different factors contributing to amplification process fail, because current databases of DNA copy number aberrations and fragile sites comprise conventional cytogenetics results obtained at far too coarse chromosome band resolution. Array comparative genomic hybridization (aCGH) enables genome-wide gene copy number measurements and amplification detection at molecular genetic resolution. Similarly, cloning and sequencing of fragile sites produce mapping information of vastly improved resolution. In conclusion, databases of aCGH and sequenced fragile sites are needed to resolve the mechanisms of gene amplifications in systems biology configuration.

Chromosome Aberrations↗
PubMed2005

Endotoxin recognition: in fish or not in fish?

The interaction between pathogens and their multicellular hosts is initiated by activation of pathogen recognition receptors (PRRs). These receptors, that include most notably members of the toll-like receptor (TLR) family, recognize specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part of the receptor complex that is involved in the activation of the immune system by lipopolysaccharide (LPS) through the specific recognition of its endotoxic moiety (Lipid A). This is a critical event that is essential for the immune response to Gram-negative bacteria as well as the etiology of endotoxic shock. Interestingly, compared to mammals, fish are resistant to endotoxic shock. This in vivo resistance concurs with in vitro studies demonstrating significantly lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce antiviral genes, an event that occurs downstream of TLR4 and is required for the development of endotoxic shock. Finally, an in silico approach that includes mining of different piscine genomic and EST databases, reveals the presence in fish of all of the major TLR signaling elements except for the molecules specifically involved in TLR4-mediated endotoxin recognition and signaling in mammals. Collectively, our analysis questions the existence of TLR4-mediated cellular responses to LPS in fish. We further speculate that other receptors, in particular beta-2 integrins, may play a primary role in the activation of piscine leukocytes by LPS.

Animals↗
PubMed2026

Elevated Triggering Receptor Expressed on Myeloid Cells 2 Expression in Tumor-Associated Macrophages Suppresses Cytotoxic T Cell Infiltration and Facilitates Immune Escape in Colorectal Cancer.

BACKGROUND & AIMS: Emerging evidence supports a crucial role for tumor-associated macrophages in shaping the immunosuppressive tumor microenvironment. Furthermore, research has identified that the triggering receptor expressed on myeloid cells 2 has immunomodulatory functions. The present investigated the potential effect of triggering receptor expressed on myeloid cells 2 expression in tumor-associated macrophages on facilitating immune evasion in colorectal cancer. METHODS: Immunohistochemical analysis of clinical specimens, complemented by extensive data mining from The Cancer Genome Atlas, revealed a significant upregulation of triggering receptor expressed on myeloid cells 2 in colorectal cancer-associated tumor-associated macrophages, with this upregulation exhibiting a correlation with poor patient prognosis. RESULTS: Mechanistically, triggering receptor expressed on myeloid cells 2+ tumor-associated macrophages were found to drive fibroblast activation through transforming growth factor-β signaling, inducing fibroblast-activated protein-positive cancer-associated fibroblasts that secrete collagen I/III to establish dense peritumoral barriers. Spatial profiling revealed that these fibrous structures physically impede CD8+ T-cell infiltration, restricting cytotoxic lymphocytes to stromal compartments. Intriguingly, triggering receptor expressed on myeloid cells 2 deficiency enhanced the secretion of matrix metalloproteinase 13 by macrophages, thereby promoting extracellular matrix degradation and improving T-cell penetration. In vivo, Trem2-knockout mice showed a reduction in tumor growth with enhanced intratumoral CD8+ T-cell infiltration compared with wild-type controls. CONCLUSIONS: Our findings establish triggering receptor expressed on myeloid cells 2+ tumor-associated macrophages as central regulators of stromal remodeling and suggest that therapeutic targeting of the triggering receptor expressed on myeloid cells 2/transforming growth factor-β/fibroblast-activated protein pathway may overcome immune resistance in patients with colorectal cancer.

Colorectal Neoplasms↗
PubMed2005

Characterization of a rice class II metallothionein gene: tissue expression patterns and induction in response to abiotic factors.

Data mining the complete rice genome sequences revealed a genomic fragment encoding a characteristic metallothionein (MT) protein, and its full-length cDNA was isolated from rice developing seeds by RT-PCR. This cDNA, designated OsMT-II-1a, contains an open reading frame of 264 bp encoding a protein of 87 amino acid residues. The predicted amino acid sequence was shown to have structural features characteristic of plant class II MT proteins. By sequence analysis of its 5'-flanking region, one putative TATA box, four putative CAAT boxes, and several short sequences homologous to previously reported regulatory cis-elements were identified. Northern blot analysis showed that accumulation of OsMT-II-1a mRNA is specifically abundant in developing seeds and 2-day glumes after pollination, and OsMT-II-1a transcription can markedly be induced by H2O2, paraquat, SNP, ethephon, ABA and SA, but barely by metal ions or other exogenous abiotic factors such as low temperature and PEG. These results coincide with the prediction of existing regulatory cis-elements in its 5'-flanking region. Taken together, the above results suggest that the processes of pollination and seed development might be mediated, at least in part, by expression of the OsMT-II-1a gene that is regulated by several abiotic factors.

Amino Acid Sequence↗