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Bioinformatics Approaches (bioinformatics + approach)
Selected AbstractsMultiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancersGENES, CHROMOSOMES AND CANCER, Issue 11 2007Wennuan Liu A number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele-specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu-Sq and Alu-Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer. © 2007 Wiley-Liss, Inc. [source] Bioinformatic analysis of the hepadnavirus e-antigen and its precursor identifies remarkable sequence conservation in all orthohepadnavirusesJOURNAL OF MEDICAL VIROLOGY, Issue 1 2010Peter Revill Abstract The hepatitis B e-antigen (HBeAg) is a non-particulate secretory protein expressed by all viruses within the family Hepadnaviridae. It is not essential for viral assembly or replication but is important for establishment of persistent infection in vivo. Although the exact mechanism(s) by which the HBeAg manifests chronicity are unclear, the HBeAg elicits both humoral and cell-mediated immunity, down-regulates the innate immune response to infection, as well as functioning as a T cell tolerogen and regulating the immune response to the intracellular nucleocapsid. A bioinformatics approach was used to show that the HBeAg and precursory genetic codes share remarkable sequence conservation in all mammalian-infecting hepadnaviruses, irrespective of host, genotype, or geographic origin. Whilst much of this sequence conservation was within key immunomodulatory epitopes, highest conservation was observed at the unique HBeAg N-terminus, suggesting this sequence in particular may play an important role in HBeAg function. J. Med. Virol. 82:104,115, 2010. © 2009 Wiley-Liss, Inc. [source] Ethanol Alters the Osteogenic Differentiation of Amniotic Fluid-Derived Stem CellsALCOHOLISM, Issue 10 2010Jennifer A. Hipp Background:, Fetal alcohol spectrum disorder (FASD) is a set of developmental defects caused by prenatal alcohol exposure. Clinical manifestations of FASD are highly variable and include mental retardation and developmental defects of the heart, kidney, muscle, skeleton, and craniofacial structures. Specific effects of ethanol on fetal cells include induction of apoptosis as well as inhibition of proliferation, differentiation, and migration. This complex set of responses suggests that a bioinformatics approach could clarify some of the pathways involved in these responses. Methods:, In this study, the responses of fetal stem cells derived from the amniotic fluid (AFSCs) to treatment with ethanol have been examined. Large-scale transcriptome analysis of ethanol-treated AFSCs indicates that genes involved in skeletal development and ossification are up-regulated in these cells. Therefore, the effect of ethanol on osteogenic differentiation of AFSCs was studied. Results:, Exposure to ethanol during the first 48 hours of an osteogenic differentiation protocol increased in vitro calcium deposition by AFSCs and increased alkaline phosphatase activity. In contrast, ethanol treatment later in the differentiation protocol (day 8) had no significant effect on the activity of alkaline phosphatase. Conclusions:, These results suggest that transient exposure of AFSCs to ethanol during early differentiation enhances osteogenic differentiation of the cells. [source] Computer programming and biomolecular structure studies: A step beyond internet bioinformaticsBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 1 2006Vladimir A. Liki Abstract This article describes the experience of teaching structural bioinformatics to third year undergraduate students in a subject titled Biomolecular Structure and Bioinformatics. Students were introduced to computer programming and used this knowledge in a practical application as an alternative to the well established Internet bioinformatics approach that relies on access to the Internet and biological databases. This was an ambitious approach considering that the students mostly had a biological background. There were also time constraints of eight lectures in total and two accompanying practical sessions. The main challenge was that students had to be introduced to computer programming from a beginner level and in a short time provided with enough knowledge to independently solve a simple bioinformatics problem. This was accomplished with a problem directly relevant to the rest of the subject, concerned with the structure-function relationships and experimental techniques for the determination of macromolecular structure. [source] Discovery of Selective Irreversible Inhibitors for Bruton's Tyrosine KinaseCHEMMEDCHEM, Issue 1 2007Zhengying Pan Dr. A series of highly selective irreversible inhibitors for Bruton's tyrosine kinase (Btk) was developed using a structural bioinformatics approach. Their capabilities to modulate Btk's activity were characterized both in,vitro and in,vivo. Oral treatment with once-a-day dosing of compound 4 greatly inhibited disease development in a rodent rheumatoid arthritis (RA) model. [source] Nitrogenase gene diversity and microbial community structure: a cross-system comparisonENVIRONMENTAL MICROBIOLOGY, Issue 7 2003Jonathan P. Zehr Summary Biological nitrogen fixation is an important source of fixed nitrogen for the biosphere. Microorganisms catalyse biological nitrogen fixation with the enzyme nitrogenase, which has been highly conserved through evolution. Cloning and sequencing of one of the nitrogenase structural genes, nifH, has provided a large, rapidly expanding database of sequences from diverse terrestrial and aquatic environments. Comparison of nifH phylogenies to ribosomal RNA phylogenies from cultivated microorganisms shows little conclusive evidence of lateral gene transfer. Sequence diversity far outstrips representation by cultivated representatives. The phylogeny of nitrogenase includes branches that represent phylotypic groupings based on ribosomal RNA phylogeny, but also includes paralogous clades including the alternative, non-molybdenum, non-vanadium containing nitrogenases. Only a few alternative or archaeal nitrogenase sequences have as yet been obtained from the environment. Extensive analysis of the distribution of nifH phylotypes among habitats indicates that there are characteristic patterns of nitrogen fixing microorganisms in termite guts, sediment and soil environments, estuaries and salt marshes, and oligotrophic oceans. The distribution of nitrogen-fixing microorganisms, although not entirely dictated by the nitrogen availability in the environment, is non-random and can be predicted on the basis of habitat characteristics. The ability to assay for gene expression and investigate genome arrangements provides the promise of new tools for interrogating natural populations of diazotrophs. The broad analysis of nitrogenase genes provides a basis for developing molecular assays and bioinformatics approaches for the study of nitrogen fixation in the environment. [source] New directions and interactions in metagenomics researchFEMS MICROBIOLOGY ECOLOGY, Issue 3 2006Naomi Ward Abstract Metagenomics, which aims to access the genomic potential of an environmental sample directly, is a burgeoning area that is generating enormous amounts of biological information. An examination of recent metagenomics literature reveals the discipline to be heading in new and interesting directions, including the investigation of the normal flora of mammals, analysis of ancient genomes, and exploration of the distribution of novel pathways. In addition, the development of new bioinformatics approaches and tools is allowing innovative mining of both existing and new data. Finally, there are indications that the integration of metagenomics with complementary approaches in microbial ecology is beginning. [source] Automated protein identification by tandem mass spectrometry: Issues and strategiesMASS SPECTROMETRY REVIEWS, Issue 2 2006Patricia Hernandez Abstract Protein identification by tandem mass spectrometry (MS/MS) is key to most proteomics projects and has been widely explored in bioinformatics research. Obtaining good and trustful identification results has important implications for biological and clinical work. Although well matured, automated software identification of proteins from MS/MS data still faces a number of obstacles due to the complexity of the proteome or procedural issues of mass spectrometry data acquisition. Expected or unexpected modifications of the peptide sequences, polymorphisms, errors in databases, missed or non-specific cleavages, unusual fragmentation patterns, and single MS/MS spectra of multiple peptides of the same m/z are so many pitfalls for identification algorithms. A lot of research work has been carried out in recent years that yielded new strategies to handle a number of these issues. Multiple MS/MS identification algorithms are now available or have been theoretically described. The difficulty resides in choosing the most adapted method for each type of spectra being identified. This review presents an overview of the state-of-the-art bioinformatics approaches to the identification of proteins by MS/MS to help the reader doing the spadework of finding the right tools among the many possibilities offered. © 2005 Wiley Periodicals, Inc. Mass Spec Rev 25:235,254, 2006 [source] De novo sulfur SAD phasing of the lysosomal 66.3,kDa protein from mouseACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2009Kristina Lakomek The 66.3,kDa protein from mouse is a soluble protein of the lysosomal matrix. It is synthesized as a glycosylated 75,kDa preproprotein which is further processed into 28 and 40,kDa fragments. Despite bioinformatics approaches and molecular characterization of the 66.3,kDa protein, the mode of its maturation as well as its physiological function remained unknown. Therefore, it was decided to tackle this question by means of X-ray crystallography. After expression in a human fibrosarcoma cell line, the C-terminally His-tagged single-chain 66.3,kDa variant and the double-chain form consisting of a 28,kDa fragment and a 40,kDa fragment were purified to homogeneity but could not be separated during the purification procedure. This mixture was therefore used for crystallization. Single crystals were obtained and the structure of the 66.3,kDa protein was solved by means of sulfur SAD phasing using data collected at a wavelength of 1.9,Å on the BESSY beamline BL14.2 of Freie Universität Berlin. Based on the anomalous signal, a 22-atom substructure comprising 21 intrinsic S atoms and one Xe atom with very low occupancy was found and refined at a resolution of 2.4,Å using the programs SHELXC/D and SHARP. Density modification using SOLOMON and DM resulted in a high-quality electron-density map, enabling automatic model building with ARP/wARP. The initial model contained 85% of the amino-acid residues expected to be present in the asymmetric unit of the crystal. Subsequently, the model was completed and refined to an Rfree factor of 19.8%. The contribution of the single Xe atom to the anomalous signal was analyzed in comparison to that of the S atoms and was found to be negligible. This work should encourage the use of the weak anomalous scattering of intrinsic S atoms in SAD phasing, especially for proteins, which require both expensive and time-consuming expression and purification procedures, preventing extensive screening of heavy-atom crystal soaks. [source] Can molecular mechanisms of biological processes be extracted from expression profiles?BIOESSAYS, Issue 12 2001Case study: endothelial contribution to tumor-induced angiogenesis Whereas the genome contains all potential developmental programs, expression profiles permit the determination of genes that are actively transcribed under defined physiological conditions. In this article, the idea of extracting biological mechanisms from expression data is tested. Molecular processes of the endothelial contribution to angiogenesis are derived from recently published expression profiles. The analysis reveals the sensitivity limits of experimental detection of transcriptional changes and how sequence-analytic techniques can help to identify the function of genes in question. We conclude that the transcripts (http://mendel.imp.univie.ac.at/SEQUENCES/TEMS/) found to be up-regulated in angiogenesis are involved in extracellular matrix remodeling, cellular migration, adhesion, cell-cell communication rather than in angiogenesis initiation or integrative control. Comparison with tissue-specific patterns of EST occurrence shows that, indeed, the presumptive tumor-specific endothelial markers are more generally expressed by cell types involved in migration and matrix remodeling processes. This exemplary study demonstrates how bioinformatics approaches can be helpful in deriving mechanistic information from diverse sources of experimental data. BioEssays 23:1159,1175, 2001. © 2001 John Wiley & Sons, Inc. [source] DATE analysis: A general theory of biological change applied to microarray dataBIOTECHNOLOGY PROGRESS, Issue 5 2009David Rasnick Abstract In contrast to conventional data mining, which searches for specific subsets of genes (extensive variables) to correlate with specific phenotypes, DATE analysis correlates intensive state variables calculated from the same datasets. At the heart of DATE analysis are two biological equations of state not dependent on genetic pathways. This result distinguishes DATE analysis from other bioinformatics approaches. The dimensionless state variable F quantifies the relative overall cellular activity of test cells compared to well-chosen reference cells. The variable ,i is the fold-change in the expression of the ith gene of test cells relative to reference. It is the fraction , of the genome undergoing differential expression,not the magnitude ,,that controls biological change. The state variable , is equivalent to the control strength of metabolic control analysis. For tractability, DATE analysis assumes a linear system of enzyme-connected networks and exploits the small average contribution of each cellular component. This approach was validated by reproducible values of the state variables F, RNA index, and , calculated from random subsets of transcript microarray data. Using published microarray data, F, RNA index, and , were correlated with: (1) the blood-feeding cycle of the malaria parasite, (2) embryonic development of the fruit fly, (3) temperature adaptation of Killifish, (4) exponential growth of cultured S. pneumoniae, and (5) human cancers. DATE analysis was applied to aCGH data from the great apes. A good example of the power of DATE analysis is its application to genomically unstable cancers, which have been refractory to data mining strategies. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] | ||||||||||||||||