DegNorm: normalization of generalized transcript degradation improves accuracy in RNA-seq analysis

Abstract

Abstract RNA degradation affects RNA-seq quality when profiling transcriptional activities in cells. Here, we show that transcript degradation is both gene- and sample-specific and is a common and significant factor that may bias the results in RNA-seq analysis. Most existing global normalization approaches are ineffective to correct for degradation bias. We propose a novel pipeline named DegNorm to adjust the read counts for transcript degradation heterogeneity on a gene-by-gene basis while simultaneously controlling for the sequencing depth. The robust and effective performance of this method is demonstrated in an extensive set of simulated and real RNA-seq data.

Keywords

• RNA-seq
• Normalization
• RNA degradation
• Degradation normalization
• Alternative splicing
• Non-negative matrix factorization