Augmenting precision medicine via targeted RNA-Seq detection of expressed mutations

Summary:
This study explores how targeted RNA sequencing (RNA-seq) can complement or even independently detect clinically relevant mutations in cancer, especially those missed by DNA sequencing alone.

Key Insights:

RNA panels can confirm expression of DNA variants, helping prioritize mutations that are biologically active and potentially actionable.

Unexpressed variants and variants not detected by RNA-seq may be less clinically important for many health contexts, a critical consideration for personalized vaccine development.

Targeted RNA-seq panels typically offer more sensitivity for variants covered by the panels than whole transcriptome sequencing (WTS), an important consideration for assay choice.

Bioinformatics matters:  False positives vary by panel and caller but can be minimized with careful filtering and method selection.

Variants found only by RNA-seq have value:  variants identified only by RNA-seq in this study include many with known or predicted clinical significance, reinforcing RNA-seq’s value in precision oncology.

This work provides a technical foundation for integrating RNA-seq into clinical workflows, improving the accuracy of mutation profiling, and refining therapeutic targeting, especially in the context of cancer immunotherapy and neoantigen selection.

Explore the full methodology, results, and implications for integrating RNA-seq into clinical workflows.