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      Comparative analysis of bat genomes provides insight into the evolution of flight and immunity.

      Science (New York, N.Y.)
      Amino Acid Sequence, Animals, Biological Evolution, Chiroptera, genetics, immunology, physiology, DNA Damage, DNA Repair, Echolocation, Evolution, Molecular, Flight, Animal, Genetic Speciation, Genome, Hibernation, High-Throughput Nucleotide Sequencing, Immunity, Innate, Male, Molecular Sequence Data, Phylogeny, Reactive Oxygen Species, metabolism, Selection, Genetic, Sequence Analysis, DNA, Species Specificity

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          Abstract

          Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

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          Most cited references29

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          NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?

          The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and IL-18. The NLRP3 inflammasome is activated by a wide range of danger signals that derive not only from microorganisms but also from metabolic dysregulation. It is unclear how these highly varied stress signals can be detected by a single inflammasome. In this Opinion article, we review the different signalling pathways that have been proposed to engage the NLRP3 inflammasome and suggest a model in which one of the crucial elements for NLRP3 activation is the generation of reactive oxygen species (ROS).
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            Ab initio gene finding in Drosophila genomic DNA.

            Ab initio gene identification in the genomic sequence of Drosophila melanogaster was obtained using (human gene predictor) and Fgenesh programs that have organism-specific parameters for human, Drosophila, plants, yeast, and nematode. We did not use information about cDNA/EST in most predictions to model a real situation for finding new genes because information about complete cDNA is often absent or based on very small partial fragments. We investigated the accuracy of gene prediction on different levels and designed several schemes to predict an unambiguous set of genes (annotation CGG1), a set of reliable exons (annotation CGG2), and the most complete set of exons (annotation CGG3). For 49 genes, protein products of which have clear homologs in protein databases, predictions were recomputed by Fgenesh+ program. The first annotation serves as the optimal computational description of new sequence to be presented in a database. Reliable exons from the second annotation serve as good candidates for selecting the PCR primers for experimental work for gene structure verification. Our results shows that we can identify approximately 90% of coding nucleotides with 20% false positives. At the exon level we accurately predicted 65% of exons and 89% including overlapping exons with 49% false positives. Optimizing accuracy of prediction, we designed a gene identification scheme using Fgenesh, which provided sensitivity (Sn) = 98% and specificity (Sp) = 86% at the base level, Sn = 81% (97% including overlapping exons) and Sp = 58% at the exon level and Sn = 72% and Sp = 39% at the gene level (estimating sensitivity on std1 set and specificity on std3 set). In general, these results showed that computational gene prediction can be a reliable tool for annotating new genomic sequences, giving accurate information on 90% of coding sequences with 14% false positives. However, exact gene prediction (especially at the gene level) needs additional improvement using gene prediction algorithms. The program was also tested for predicting genes of human Chromosome 22 (the last variant of Fgenesh can analyze the whole chromosome sequence). This analysis has demonstrated that the 88% of manually annotated exons in Chromosome 22 were among the ab initio predicted exons. The suite of gene identification programs is available through the WWW server of Computational Genomics Group at http://genomic.sanger.ac.uk/gf. html.
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              TEclass--a tool for automated classification of unknown eukaryotic transposable elements.

              The large number of sequenced genomes required the development of software that reconstructs the consensus sequences of transposons and other repetitive elements. However, the available tools usually focus on the accurate identification of raw repeats and provide no information about the taxonomic position of the reconstructed consensi. TEclass is a tool to classify unknown transposable elements into their four main functional categories, which reflect their mode of transposition: DNA transposons, long terminal repeats (LTRs), long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). TEclass uses machine learning support vector machine (SVM) for classification based on oligomer frequencies. It achieves 90-97% accuracy in the classification of novel DNA and LTR repeats, and 75% for LINEs and SINEs. http://www.compgen.uni-muenster.de/teclass, stand alone program upon request.
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