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Quantifying defective and wild-type viruses from high-throughput RNA sequencing.

Juan C Muñoz-Sánchez1,2, María J Olmo-Uceda1, José-Ángel Oteo1,2

  • 1Institute for Integrative Systems Biology (I2SysBio), CSIC-Universitat de València, Paterna, València 46980, Spain.

Bioinformatics (Oxford, England)
|November 4, 2024
PubMed
Summary
This summary is machine-generated.

This study introduces a novel method for quantifying defective viral genomes (DVGs) alongside wild-type (wt) viruses. The new approach accurately estimates DVG and wt genome proportions from RNA sequencing data, crucial for understanding viral evolution and infection.

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Area of Science:

  • Virology
  • Genomics
  • Bioinformatics

Background:

  • Defective viral genomes (DVGs) are viral variants that require a helper wild-type (wt) virus for replication.
  • DVGs influence viral evolution, host immune responses, and infection outcomes, making their quantification critical.
  • Accurate quantification of DVGs is challenging due to their dependence on wt viruses and difficulties in distinguishing them in sequencing data.

Purpose of the Study:

  • To develop a method for simultaneously estimating the abundances of DVGs and wt genomes.
  • To enable genome-wide quantification of DVG and wt proportions from short-read RNA sequencing data.

Main Methods:

  • Developed a computational method to estimate viral genome abundances by identifying deviations in sequencing depth.
  • Utilized a linear system of equations to reconstruct depth profiles and quantify wt and DVG genomes.
  • The method provides genome-wide estimates, unlike previous region-specific approaches.

Main Results:

  • Successfully developed a method for simultaneous estimation of wt and DVG genome abundances.
  • The approach accurately quantifies proportions of both genome types from RNA sequencing data.
  • This is the first method to provide genome-wide simultaneous quantification of wt and DVGs.

Conclusions:

  • The developed method offers a significant advancement in quantifying DVGs and wt viruses.
  • Accurate quantification is essential for understanding DVG dynamics and their impact on viral infections.
  • The freely available code and datasets facilitate further research in this area.