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A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes.

ABSTRACT: MOTIVATION: Animal toxins operate by binding to receptors and ion channels. These proteins are short and vary in sequence, structure and function. Sporadic discoveries have also revealed endogenous toxin-like proteins in non-venomous organisms. Viral proteins are the largest group of quickly evolving proteomes. We tested the hypothesis that toxin-like proteins exist in viruses and that they act to modulate functions of their hosts. RESULTS: We updated and improved a classifier for compact proteins resembling short animal toxins that is based on a machine-learning method. We applied it in a large-scale setting to identify toxin-like proteins among short viral proteins. Among the approximately 26 000 representatives of such short proteins, 510 sequences were positively identified. We focused on the 19 highest scoring proteins. Among them, we identified conotoxin-like proteins, growth factors receptor-like proteins and anti-bacterial peptides. Our predictor was shown to enhance annotation inference for many 'uncharacterized' proteins. We conclude that our protocol can expose toxin-like proteins in unexplored niches including metagenomics data and enhance the systematic discovery of novel cell modulators for drug development. AVAILABILITY: ClanTox is available at http://www.clantox.cs.huji.ac.il.

SUBMITTER: Naamati G

PROVIDER: S-EPMC2935411 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes.

Naamati Guy G Askenazi Manor M Linial Michal M

Bioinformatics (Oxford, England) 20100901 18

<h4>Motivation</h4>Animal toxins operate by binding to receptors and ion channels. These proteins are short and vary in sequence, structure and function. Sporadic discoveries have also revealed endogenous toxin-like proteins in non-venomous organisms. Viral proteins are the largest group of quickly evolving proteomes. We tested the hypothesis that toxin-like proteins exist in viruses and that they act to modulate functions of their hosts.<h4>Results</h4>We updated and improved a classifier for c ...[more]

PMID: 20823311

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Project description:Phylogenetic relationships among snails (Caenogastropoda) are still unresolved, and many taxonomic categories remain non-monophyletic. Paraphyly has been reported within a large family of freshwater snails, Viviparidae, where the taxonomic status of several species remains questionable. As many endemic Chinese viviparid species have become endangered during the last few decades, this presents a major obstacle for conservation efforts. Mitochondrial genomes (mitogenomes) carry a large amount of data, so they can often provide a much higher resolution for phylogenetic analyses in comparison to the traditionally used molecular markers. To help resolve their phylogenetic relationships, the complete mitogenomes of eight Chinese viviparid snails, Viviparus chui, Cipangopaludina chinensis, C. ussuriensis, C. dianchiensis (endangered), Margarya melanioides (endangered), M. monodi (critically endangered), Bellamya quadrata and B. aeruginosa, were sequenced and compared to almost all of the available caenogastropod mitogenomes. Viviparidae possess the largest mitogenomes (16 392 to 18 544 bp), exhibit the highest A+T bias (72.5% on average), and some exhibit unique gene orders (a rearrangement of the standard MYCWQGE box), among the Caenogastropoda. Apart from the Vermetidae family and Cerithioidea superfamily, which possessed unique gene orders, the remaining studied caenogastropod mitogenomes exhibited highly conserved gene order, with minimal variations. Maximum likelihood and Bayesian inference analyses, used to reconstruct the phylogenetic relationships among 49 almost complete (all 37 genes) caenogastropod mitogenomes, produced almost identical tree topologies. Viviparidae were divided into three clades: a) Margarya and Cipangopaludina (except C. ussuriensis), b) Bellamya and C. ussuriensis, c) Viviparus chui. Our results present evidence that some Cipangopaludina species (dianchiensis and cathayensis) should be renamed into the senior genus Margarya. The phylogenetic resolution obtained in this study is insufficient to fully resolve the relationships within the 'b' clade, but if C. chinensis proves to be a valid representative of the genus, C. ussuriensis may have to be reassigned a different genus (possibly Bellamya, or even a new genus). Non-monophyly also remains pervasive among the higher (above the family-level) Caenogastropod taxonomic classes. Gene order distance matrix produced a different phylogenetic signal from the nucleotide sequences, which indicates a limited usability of this approach for inferring caenogastropod phylogenies. As phenotypic homoplasy appears to be widespread among some viviparid genera, in order to effectively protect the rapidly diminishing endemic Viviparid populations in China, further detailed molecular phylogenetic studies are urgently needed to resolve the taxonomic status of several species.

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A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes.

Publications

A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes.

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