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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
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Virus Pop-Expanding Viral Databases by Protein Sequence Simulation.

Julia Kende1, Massimiliano Bonomi2, Sarah Temmam3

  • 1Bioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris Cité, F-75015 Paris, France.

Viruses
|June 28, 2023
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Summary
This summary is machine-generated.

Virus Pop simulates realistic viral protein sequences to improve metagenomic tools. This pipeline enhances viral discovery by challenging taxonomic assignation and expanding databases for detecting novel viruses.

Keywords:
amino acid substitution ratesdatabasephylogenomicssequence evolutionsequence simulation

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Area of Science:

  • Virology
  • Bioinformatics
  • Computational Biology

Background:

  • Metagenomic tools are crucial for identifying unknown viruses but are typically evaluated using known sequences.
  • Current evaluation methods limit the assessment of tools' ability to detect novel or distantly related viruses.
  • Expanding public databases with realistic simulated sequences can improve the detection of viruses with limited representation.

Purpose of the Study:

  • To introduce Virus Pop, a novel pipeline for simulating realistic protein sequences and phylogenetic trees.
  • To enhance the benchmarking of metagenomic tools for viral discovery.
  • To improve the detection of novel and distantly related viruses by expanding sequence databases.

Main Methods:

  • Virus Pop simulates protein sequences with domain-specific substitution rate variations.
  • The pipeline infers ancestral sequences and inserts new simulated sequences into phylogenetic trees.
  • The tool was validated using the spike protein of sarbecoviruses and for detecting a novel human circovirus.

Main Results:

  • Virus Pop generates simulated sequences that accurately reflect the structural and functional properties of real viral proteins.
  • Simulated sequences closely matched real protein sequences, including those not present in public databases.
  • The pipeline successfully aided in identifying a novel pathogenic human circovirus.

Conclusions:

  • Virus Pop provides a valuable method for challenging and improving taxonomic assignation tools in metagenomics.
  • The pipeline can enhance viral databases, leading to better detection of distant and previously unknown viruses.
  • Virus Pop contributes to characterizing the "dark matter" of metagenomic data.