Since all translocations in TICdb are mapped to specific introns or exons, we were able to check whether the exons flanking a translocation breakpoint have compatible reading frames, that is, if the last exon of the 5' partner gene ends in the same reading frame in which the first exon of the 3' partner gene starts.
This is achieved by translating the enzymes from a single open reading frame, in which the individual proteins are separated by a viral peptide signal (2A).
The presence of such a barrier can dramatically increase the probability that the ribosome will shift into an alternate reading frame, in which a different set of codons is recognized.
Briefly, each contig consensus was compared against the NCBI protein database using BLASTX to establish a reading frame in which to assess synonymous or non-synonymous status.
Each exon is associated with a reading frame in which translation is expected to occur.
After sequence reconstruction we assess the preservation of the reading frame in the chimeric transcript, which enables a great deal of our downstream feature engineering (see Figure 4a).
Ribosomal frameshifting, which has been demonstrated in Euplotes (for review, see [ 36]), or suppressed nonsense mutations have been proposed to repair the 5' end of the reading frame, which contains an in-frame stop codon near the previously assigned translation initiation sites in S. lemnae [ 35], S. histriomuscorum, and S. nova [ 37, 38].
These clinical differences are intriguing, given that both 458dupA and 460dupA disrupt the same restriction site and lead to a shift in the reading frame which lengthens the ferritin light polypeptide by four residues.
Collectively, 85% of the indels observed in this study resulted in frame shift mutations (±1 or ±2 bp) in the reading frame (Fig. 4B), which most likely leads to a loss-of-function of the target protein.
A frameshift mutation is an insertion or deletion in the coding sequence which changes the reading frame resulting in a different translation of the subsequent sequence.
