Computational methods for systematically characterizing putative protein isoforms as apparent targets of nonsense-mediated decay (NMD) comprise: (a) identifying a dataset of target putative protein isoform sequences for characterization; (b) identifying from an mRNA dataset corresponding mRNA sequences representing transcripts encoding the protein isoforms; (c) determining corresponding gene intron-exon structures by mapping the mRNA sequences to corresponding genomic sequences; and (d) determining if the transcripts are apparent targets of NMD. Methods for regulating the expression of a gene encoding a protein isoform characterized as an apparent target of NMD comprise biasing expression of the isoform by modulating transcript splicing or modulating NMD activity.