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Retained introns in long RNA-seq reads are not reliably detected in sample-matched short reads

BACKGROUND: There is growing interest in retained introns in a variety of disease contexts including cancer and aging. Many software tools have been developed to detect retained introns from short RNA-seq reads, but reliable detection is complicated by overlapping genes and transcripts as well as th...

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Detalles Bibliográficos
Autores principales: David, Julianne K., Maden, Sean K., Wood, Mary A., Thompson, Reid F., Nellore, Abhinav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652823/
https://www.ncbi.nlm.nih.gov/pubmed/36369064
http://dx.doi.org/10.1186/s13059-022-02789-6
Descripción
Sumario:BACKGROUND: There is growing interest in retained introns in a variety of disease contexts including cancer and aging. Many software tools have been developed to detect retained introns from short RNA-seq reads, but reliable detection is complicated by overlapping genes and transcripts as well as the presence of unprocessed or partially processed RNAs. RESULTS: We compared introns detected by 8 tools using short RNA-seq reads with introns observed in long RNA-seq reads from the same biological specimens. We found significant disagreement among tools (Fleiss’ [Formula: see text] ) such that 47.7% of all detected intron retentions were not called by more than one tool. We also observed poor performance of all tools, with none achieving an F1-score greater than 0.26, and qualitatively different behaviors between general-purpose alternative splicing detection tools and tools confined to retained intron detection. CONCLUSIONS: Short-read tools detect intron retention with poor recall and precision, calling into question the completeness and validity of a large percentage of putatively retained introns called by commonly used methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02789-6.