24 research outputs found

    AST: An Automated Sequence-Sampling Method for Improving the Taxonomic Diversity of Gene Phylogenetic Trees

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    A challenge in phylogenetic inference of gene trees is how to properly sample a large pool of homologous sequences to derive a good representative subset of sequences. Such a need arises in various applications, e.g. when (1) accuracy-oriented phylogenetic reconstruction methods may not be able to deal with a large pool of sequences due to their high demand in computing resources; (2) applications analyzing a collection of gene trees may prefer to use trees with fewer operational taxonomic units (OTUs), for instance for the detection of horizontal gene transfer events by identifying phylogenetic conflicts; and (3) the pool of available sequences is biased towards extensively studied species. In the past, the creation of subsamples often relied on manual selection. Here we present an Automated sequence-Sampling method for improving the Taxonomic diversity of gene phylogenetic trees, AST, to obtain representative sequences that maximize the taxonomic diversity of the sampled sequences. To demonstrate the effectiveness of AST, we have tested it to solve four problems, namely, inference of the evolutionary histories of the small ribosomal subunit protein S5 of E. coli, 16 S ribosomal RNAs and glycosyl-transferase gene family 8, and a study of ancient horizontal gene transfers from bacteria to plants. Our results show that the resolution of our computational results is almost as good as that of manual inference by domain experts, hence making the tool generally useful to phylogenetic studies by non-phylogeny specialists. The program is available at http://csbl.bmb.uga.edu/~zhouchan/AST.php

    AST algorithm.

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    <p>(a) Workflow of the AST algorithm. (b) An example of the sampling procedure of AST. Each circle represents one taxon: C-all <i>Cellular Organism</i>; A-<i>Archaea</i>; B-<i>Bacteria</i>; A1 is an archaeal taxon labeled as A1, similar for A2, A3, B1, and B2. The number listed on the left shoulder of the circle (outside the rectangle) is the number of sequences from the taxon labeled in the circle, and the number listed on the right shoulder of each circle is the number of sampled sequences by AST from the taxon in the circle. In this example there are a total of 11 homologous sequences in all cellular organisms, among which 8 belong to archaea, 3 from bacteria and none from eukaryotes.</p

    Taxonomic distributions at the phylum (a) and class level (b) for sub-trees of the rpS5 sequences sampled by AST, SS, and RS, respectively.

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    <p>The y-axis gives the number of phyla/classes covered by the sampled sequences, and the x-axis represents the number of sampled sequences <i>m</i>. The original non-redundant set covers 19 phyla and 33 classes (see Section 3.2.1 for details).</p

    Phylogeny of 15 representative amino acid sequences from the GT8 class-I.

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    <p>To determine the roots of trees, we randomly selected a non-GT8 sequence (GI: 15611887) as an outgroup (in black). The sequences were sampled by (a) AST; (b) Random Sampling; and (c) Similarity Sampling approaches. The Bayesian posterior probability in grouping the 3 cyanobacterial sequences with metazoa and plants in (a) is 0.99 by using MrBayes. Tree (a) reflects the diversity of class-I with 15 sequences and also indicates a potential transfer between cyanobacteria and eukaryotes, while trees in (b) and (c) are only composed of plant sequences.</p

    Glyoxylate protects against cyanide toxicity through metabolic modulation

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    Although cyanide’s biological effects are pleiotropic, its most obvious effects are as a metabolic poison. Cyanide potently inhibits cytochrome c oxidase and potentially other metabolic enzymes, thereby unleashing a cascade of metabolic perturbations that are believed to cause lethality. From systematic screens of human metabolites using a zebrafish model of cyanide toxicity, we have identified the TCA-derived small molecule glyoxylate as a potential cyanide countermeasure. Following cyanide exposure, treatment with glyoxylate in both mammalian and non-mammalian animal models confers resistance to cyanide toxicity with greater efficacy and faster kinetics than known cyanide scavengers. Glyoxylate-mediated cyanide resistance is accompanied by rapid pyruvate consumption without an accompanying increase in lactate concentration. Lactate dehydrogenase is required for this effect which distinguishes the mechanism of glyoxylate rescue as distinct from countermeasures based solely on chemical cyanide scavenging. Our metabolic data together support the hypothesis that glyoxylate confers survival at least in part by reversing the cyanide-induced redox imbalances in the cytosol and mitochondria. The data presented herein represent the identification of a potential cyanide countermeasure operating through a novel mechanism of metabolic modulation
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