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SeedMatchR: identify off-target effects mediated by siRNA seed regions in RNA-seq experiments.

Tareian Cazares1, Richard E Higgs1, Jibo Wang1

  • 1Genetic Medicine, Eli Lilly and Company, Indianapolis, IN 46225, United States.

Bioinformatics (Oxford, England)
|January 9, 2024
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Summary

SeedMatchR identifies off-target gene knockdown effects caused by small interfering RNA (siRNA) seed regions. This R package aids researchers in detecting and visualizing these effects in RNA sequencing data.

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Genomics

Background:

  • Small interfering RNA (siRNA) mediates gene knockdown by targeting mRNA transcripts.
  • Off-target effects, including seed-mediated mechanisms mimicking microRNA (miRNA) regulation, can reduce gene translation.
  • Detecting these seed-mediated off-target effects in RNA sequencing (RNA-seq) data is challenging due to limited computational tools.

Purpose of the Study:

  • To develop and introduce SeedMatchR, an R package for detecting and visualizing siRNA seed-mediated off-target effects.
  • To provide a unified resource for analyzing these off-target effects in the context of RNA-seq experiments.
  • To enhance differential gene expression analysis by incorporating predictions of seed region activity.

Main Methods:

  • Development of the SeedMatchR R package.
  • Integration with existing differential expression analysis tools like DESeq2.
  • Utilizing RNA sequencing data to identify and quantify seed-mediated off-target effects.

Main Results:

  • SeedMatchR successfully detects and visualizes seed-mediated off-target effects.
  • The package annotates differential gene expression results with predicted seed matches.
  • Demonstrated ability to identify cumulative gene expression changes attributed to siRNA seed region activity using public data.

Conclusions:

  • SeedMatchR offers a valuable tool for researchers studying siRNA off-target effects.
  • The package facilitates a more accurate interpretation of gene knockdown experiments.
  • SeedMatchR is available on CRAN with documentation on GitHub.