Estimation of splicing metrics for NMD-sensitive transcripts

Alternative splicing is commonly quantified using the Percent-Spliced-In (PSI) metric, which measures the relative abundances of alternatively spliced isoforms. However, some transcript isoforms are targeted by the nonsense-mediated decay (NMD) pathway, introducing a strong bias that leads to underestimation of their true splicing rates. To correct for this bias, we developed an analytical framework and a set of statistical models employing a linear fractional transformation depending on a single parameter capturing the degradation rate of NMD-sensitive transcripts relative to normal mRNA decay. Using Gaussian mixture models, we demonstrated a clear separation of splicing events into two cla