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PubMed2004

Variable drug metabolism genes in Arab population.

Cataloging interethnic differences in the distribution of genotypes of drug metabolic genes provides valuable information for profiling the pharmacogenetics of a population. We used PCR analysis to catalog the frequencies of alleles and genotypes for CYP1A1, NAT2, GSTs, MTHFR, MTR (MS) and NQO*1 in Arabs. The frequencies of alleles and/or genotypes for CYP1A1*2A, GSTT1 null, GSTT1 and GSTM1 double null, and GSTP1 A1578G in Arabs were significantly higher than those reported in Caucasians. However, the distribution of NAT2 acetylator phenotypes in both populations was similar. In contrast, the frequencies of MTHFR 677T allele and the combined (677+1298) genotypes for low activity were lower than those reported in Caucasians. Other alleles in Arabs, including CYP1A1 T3801C and GSTP1 A1578G were present in frequencies similar to Africans. The overall profile of variations in metabolism genes in Arabs is thus unique.

Arabs↗
PubMed2002

Statistics usage in the American Journal of Obstetrics and Gynecology: has anything changed?

OBJECTIVE: Our purpose was to compare statistical listing and usage between articles published in the American Journal of Obstetrics and Gynecology in 1994 with those published in 1999. STUDY DESIGN: All papers included in the obstetrics, fetus-placenta-newborn, and gynecology sections and the transactions of societies sections of the January through June 1999 issues of the American Journal of Obstetrics and Gynecology (volume 180, numbers 1 to 6) were reviewed for statistical usage. Each paper was given a rating for the cataloging of applied statistics and a rating for the appropriateness of statistical usage, when possible. These results were compared with the data collected on a similar review of articles published in 1994. RESULTS: Of the 238 available articles, 195 contained statistics and were reviewed. In comparison to the articles published in 1994, there were significantly more articles that completely cataloged applied statistics (74.3% vs 47.4%) (P <.0001), and there was a significant improvement in appropriateness of statistical usage (56.4% vs 30.3%) (P <.0001). CONCLUSION: Changes in the Instructions to Authors regarding the description of applied statistics and probable changes in the behavior of researchers and Editors have led to an improvement in the quality of statistics in papers published in the American Journal of Obstetrics and Gynecology.

Gynecology↗
PubMed1996

Multiplex selection technique (MuST): an approach to clone transcription factor binding sites.

We have used a multiplex selection approach to construct a library of DNA-protein interaction sites recognized by many of the DNA-binding proteins present in a cell type. An estimated minimum of two-thirds of the binding sites present in a library prepared from activated Jurkat T cells represent authentic transcription factor binding sites. We used the library for isolation of "optimal" binding site probes that facilitated cloning of a factor and to identify binding activities induced within 2 hr of activation of Jurkat cells. Since a large fraction of the oligonucleotides obtained appear to represent "optimal" binding sites for sequence-specific DNA-binding proteins, it is feasible to construct a catalog of consensus binding sites for DNA-binding proteins in a given cell type. Qualitative and quantitative comparisons of the catalogs of binding site sequences from various cell types could provide valuable insights into the process of differentiation acting at the level of transcriptional control.

Amino Acid Sequence↗
PubMed2005

A proteomic analysis of human hemodialysis fluid.

The vascular compartment is an easily accessible compartment that provides an opportunity to measure analytes for diagnostic, prognostic, or therapeutic indications. Both serum and plasma have been analyzed extensively by proteomic approaches in an effort to catalog all proteins and polypeptides. Limitations of such approaches in obtaining a comprehensive catalog of proteins include the fact that a handful of proteins constitute over 90% of plasma protein content and that the renal glomeruli filter out proteins and polypeptides that are smaller than 66 kDa from blood. We chose to study hemodialysis fluid because it contains a higher concentration of small proteins and polypeptides and is also simultaneously depleted of the most abundant proteins present in blood. Using gel electrophoresis in combination with LC-MS/MS, we identified 292 proteins of which greater than 70% had not been previously identified from serum or plasma. More than half of the proteins identified from the hemodialysis fluid were smaller than 40 kDa. We also found 50 N-terminally acetylated peptides that allowed us to unambiguously map the N termini of mature forms of the corresponding proteins. Several identified proteins, including cytokines, were only present as predicted transcripts in data bases and thus represent novel proteins. The proteins identified in this study could serve as biomarkers in serum using more sensitive methods such as ELISA-specific antibodies.

Aged↗
PubMed2002

Tobacco harm reduction: conceptual structure and nomenclature for analysis and research.

The goal of tobacco control has always been to reduce death and disease due to tobacco use. Recent discussions have broadened the concept of tobacco control beyond cessation and prevention to include concepts such as the use of medications to achieve reduction in tobacco use, chemoprevention to reduce disease, modifications of tobacco products to reduce toxicity, and behavioral approaches to change smoking and tobacco use behavior. Within each of these broad domains, diverse approaches have been suggested. To facilitate clear discussion and analysis, and to avoid confusion among approaches, we catalog 19 approaches to harm reduction, distinguishing and discussing them on 11 dimensions, including their objectives, mechanisms, toxicology, expected population risks, and consumer appeal. Because there have also been so many suggested applications of medicinal nicotine to smoking intervention, we separately catalog and analyze nine applications, some of which constitute new approaches to harm reduction. The suggested framework is intended to clarify the debate, provide for common nomenclature, and facilitate analysis of diverse approaches to tobacco harm reduction.

Harm Reduction↗
PubMed2004

Generation of a total of 6483 expressed sequence tags from 60 day-old bovine whole fetus and fetal placenta.

Expressed sequence tags (ESTs) generated based on characterization of clones isolated randomly from cDNA libraries are used to study gene expression profiles in specific tissues and to provide useful information for characterizing tissue physiology. In this study, two directionally cloned cDNA libraries were constructed from 60 day-old bovine whole fetus and fetal placenta. We have characterized 5357 and 1126 clones, and then identified 3464 and 795 unique sequences for the fetus and placenta cDNA libraries: 1851 and 504 showed homology to already identified genes, and 1613 and 291 showed no significant matches to any of the sequences in DNA databases, respectively. Further, we found 94 unique sequences overlapping in both the fetus and the placenta, leading to a catalog of 4165 genes expressed in 60 day-old fetus and placenta. The catalog is used to examine expression profile of genes in 60 day-old bovine fetus and placenta.

Animals↗
PubMed1999

The Diversity of Eukaryotes.

The discipline of evolutionary protistology has emerged in the past 30 yr. There is as yet no agreed view of how protists are interrelated or how they should be classified. The foundations of a stable taxonomic superstructure for the protists and other eukaryotes lie in cataloging the diversity of the major monophyletic lineages of these organisms. The use of common patterns of cell organization (ultrastructural identity) seems to provide us with the most robust hypotheses of such lineages. These lineages are placed in 71 groups without identifiable sister taxa. These groups are here referred to as "major building blocks." For the first time, the compositions, ultrastructural identities, synapomorphies (where available), and subgroups of the major building blocks are summarized. More than 200 further lineages without clear identities are listed. This catalog includes all known major elements of the comprehensive evolutionary tree of protists and eukaryotes. Different approaches among protistologists to issues of nomenclature, ranking, and definitions of these groups are discussed, with particular reference to two groups-the stramenopiles and the Archezoa. The concept of "extended in-group" is introduced to refer to in-groups and the most proximate sister group and to assist in identifying the hierarchical location of taxa.

eukaryotes↗
PubMed2005

The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates.

The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.

Algorithms↗
PubMed2003

Deconvolving sequence variation in mixed DNA populations.

We present an original approach to identifying sequence variants in a mixed DNA population from sequence trace data. The heart of the method is based on parsimony: given a wildtype DNA sequence, a set of observed variations at each position collected from sequencing data, and a complete catalog of all possible mutations, determine the smallest set of mutations from the catalog that could fully explain the observed variations. The algorithmic complexity of the problem is analyzed for several classes of mutations, including block substitutions, single-range deletions, and single-range insertions. The reconstruction problem is shown to be NP-complete for single-range insertions and deletions, while for block substitutions, single character insertion, and single character deletion mutations, polynomial time algorithms are provided. Once a minimum set of mutations compatible with the observed sequence is found, the relative frequency of those mutations is recovered by solving a system of linear equations. Simulation results show the algorithm successfully deconvolving mutations in p53 known to cause cancer. An extension of the algorithm is proposed as a new method of high throughput screening for single nucleotide polymorphisms by multiplexing DNA.

Algorithms↗
PubMed2004

Genomic data visualization on the Web.

UNLABELLED: Many types of genomic data can be represented in matrix format, with rows corresponding to genes and columns corresponding to gene features. The heat map is a popular technique for visualizing such data, plotting the data on a two-dimensional grid and using a color scale to represent the magnitude of each matrix entry. Prism is a Web-based software tool for generating annotated heat map visualizations of genome-wide data quickly. The tool provides a selection of genome-specific annotation catalogs as well as a catalog upload capability. The heat maps generated are clickable, allowing the user to drill down to examine specific matrix entries, and gene annotations are linked to relevant genomic databases. AVAILABILITY: http://noble.gs.washington.edu/prism

Computer Graphics↗
PubMed2001

Genome and genetic resources from the Cancer Genome Anatomy Project.

The Cancer Genome Anatomy Project (CGAP) is a collaborative network of cancer researchers with a common goal: to decipher the genetic changes that occur during cancer formation and progression. The project brings together several recent technologies capable of high-throughput analysis to help achieve this goal. Automated sequencing of cDNA libraries is a primary focus and is geared towards providing a comprehensive and annotated set of human and mouse transcribed sequences. This effort includes full-length transcript sequence generated by CGAP's new Mammalian Gene Collection initiative. Single nucleotide polymorphisms (SNPs) within human gene sequences (Genetic Annotation Initiative) and chromosomal rearrangements within cancer cells (Cancer Chromosome Aberration Project) are also being cataloged as part of CGAP. Finally, to help determine gene expression patterns related to cancer, CGAP provides a quantitative catalog of data through its SAGEmap initiative. The genome and genetic analysis tools listed in this review are all freely distributed by CGAP (http://cgap.nci.nih.gov/) without restriction.

Animals↗
PubMed1999

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical diagrams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway information is also represented by the ortholog group tables summarizing orthologous and paralogous gene groups among different organisms. KEGG maintains the GENES database for the gene catalogs of all organisms with complete genomes and selected organisms with partial genomes, which are continuously re-annotated, as well as the LIGAND database for chemical compounds and enzymes. Each gene catalog is associated with the graphical genome map for chromosomal locations that is represented by Java applet. In addition to the data collection efforts, KEGG develops and provides various computational tools, such as for reconstructing biochemical pathways from the complete genome sequence and for predicting gene regulatory networks from the gene expression profiles. The KEGG databases are daily updated and made freely available (http://www.genome.ad.jp/kegg/).

Animals↗
PubMed2000

The intronerator: exploring introns and alternative splicing in Caenorhabditis elegans.

The Intronerator (http://www.cse.ucsc.edu/ approximately kent/intronerator/ ) is a set of web-based tools for exploring RNA splicing and gene structure in Caenorhabditis elegans. It includes a display of cDNA alignments with the genomic sequence, a catalog of alternatively spliced genes and a database of introns. The cDNA alignments include >100 000 ESTs and almost 1000 full-length cDNAs. ESTs from embryos and mixed stage animals as well as full-length cDNAs can be compared in the alignment display with each other and with predicted genes. The alt-splicing catalog includes 844 open reading frames for which there is evidence of alternative splicing of pre-mRNA. The intron database includes 28 478 introns, and can be searched for patterns near the splice junctions.

Alternative Splicing↗
PubMed2005

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes.

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT-PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

Animals↗
PubMed2006

MPact: the MIPS protein interaction resource on yeast.

In recent years, the Munich Information Center for Protein Sequences (MIPS) yeast protein-protein interaction (PPI) dataset has been used in numerous analyses of protein networks and has been called a gold standard because of its quality and comprehensiveness [H. Yu, N. M. Luscombe, H. X. Lu, X. Zhu, Y. Xia, J. D. Han, N. Bertin, S. Chung, M. Vidal and M. Gerstein (2004) Genome Res., 14, 1107-1118]. MPact and the yeast protein localization catalog provide information related to the proximity of proteins in yeast. Beside the integration of high-throughput data, information about experimental evidence for PPIs in the literature was compiled by experts adding up to 4300 distinct PPIs connecting 1500 proteins in yeast. As the interaction data is a complementary part of CYGD, interactive mapping of data on other integrated data types such as the functional classification catalog [A. Ruepp, A. Zollner, D. Maier, K. Albermann, J. Hani, M. Mokrejs, I. Tetko, U. Güldener, G. Mannhaupt, M. Münsterkötter and H. W. Mewes (2004) Nucleic Acids Res., 32, 5539-5545] is possible. A survey of signaling proteins and comparison with pathway data from KEGG demonstrates that based on these manually annotated data only an extensive overview of the complexity of this functional network can be obtained in yeast. The implementation of a web-based PPI-analysis tool allows analysis and visualization of protein interaction networks and facilitates integration of our curated data with high-throughput datasets. The complete dataset as well as user-defined sub-networks can be retrieved easily in the standardized PSI-MI format. The resource can be accessed through http://mips.gsf.de/genre/proj/mpact.

Databases, Protein↗
PubMed1996

Complementary classification approaches for protein sequences.

We have studied five methods of protein classification and have applied them to the 768 groups of related proteins in the PROSITE catalog. Four of these methods are based on searching a database of blocks, and the other uses the frequently occurring motifs found in the protein families combined with a fingerprint technique. Our experimental results show that the block-based methods perform well when taking into account the probability of amino acids occurring in a block. Furthermore, the five methods give information that is complementary to each other. Thus, using the five methods together, one can obtain high confidence classifications (if the results agree) or suggest alternative hypotheses (if the results disagree). We also list those proteins whose current families documented in the PROSITE catalog differ from those suggested by our results. There are remarkably few of them, which is a testimony to the quality of PROSITE.

Amino Acid Sequence↗
PubMed2006

Many expressed genes in bacteria and yeast are transcribed only once per cell cycle.

The steady-state levels of all mature transcripts expressed in bacteria and yeast have been cataloged, but we do not yet know the numbers of nascent transcripts and so RNA polymerases engaged on all genes. Such catalogs are presented here. As mRNA levels depend on the balance between synthesis and degradation, we use published data to calculate the numbers of engaged polymerases required to maintain these levels in the face of the known rate of degradation. Most genes, including essential ones, prove not to be transcribed most of the time, and many produce only one message per cell cycle. Some cells even fail to produce an essential message during a cycle, and so must depend on their mother's messages and/or proteins for survival. We speculate that evolution sets the rate of message production so low to conserve energy, minimize transcription-induced mutation, and permit regulation over the widest range.

Adaptation, Physiological↗
PubMed2003

19th-century camouflaged mechanical hearing devices.

HYPOTHESIS: The aim of this review is to present 19th century mechanical hearing devices that were designed for concealment or camouflage. BACKGROUND: Extensive literature, past and current, along with museum catalogs, trade catalogs, and advertisements, were examined to identify mechanical devices designed for concealment. METHODS: Several mechanical devices were selected for acoustic gain measurements. Measurements were made in an anechoic chamber using a Knowles Electronics Manikin for Acoustic Research fitted with a Zwislocki coupler and a pressure microphone in the right ear. One-third-octave bands of noise were presented via a KLH Model 6 loudspeaker placed at a distance of 2.23 m on-axis. The sound level at the ear of the Knowles Electronics Manikin for Acoustic Research was recorded with and without the device in place. RESULTS: A wide variety of 19th century hearing devices designed for concealment were identified. Some hearing devices, such as fans, parasols, lorgnettes, water canteens, walking sticks, chairs/thrones, hats, and books, were concealed within everyday items. Other hearing devices, such as artificial conchae, bouquet holders, and hair and beard receptors, wereconcealed on the person. The insertion gain of a representative concealed device, the Aurolese Phone, averaged approximately 3.5 dB in the range of frequencies most relevant for speech communication. CONCLUSIONS: The ingenuity behind the design of 19th century mechanical hearing devices created for concealment or camouflage is to be commended. For the Aurolese Phone, some acoustic benefit was possible despite design constraints imposed by its concealed nature.

England↗