Ratio of Amino Acid Substitution (RAAS)
Summary¶
The ratio of amino acid substitution (RAAS) quantifies the abundance of a substituted amino acid peptide relative to the corresponding canonical base peptide from the same protein. It provides an operational estimate of the relative abundance of alternatively and canonically translated proteoforms when the paired peptides differ by one amino acid [1].
Definition¶
For a substituted amino acid peptide (SAAP) and its corresponding base peptide (BP):
$$ \mathrm{RAAS} = \frac{\mathrm{abundance}(\mathrm{SAAP})}{\mathrm{abundance}(\mathrm{BP})} $$
The metric is reported on a linear scale unless explicitly written as $\log_{10}(\mathrm{RAAS})$. The DECODE pipeline sums peptide intensities across observed charge states and fractions before calculating the ratio.[1]
Interpretation¶
| RAAS value | Interpretation |
|---|---|
| Less than 1 | The substituted peptide is less abundant than the canonical base peptide. |
| Equal to 1 | The paired peptides have equal measured abundance. |
| Greater than 1 | The substituted peptide is more abundant than the canonical base peptide. |
RAAS is a peptide-pair estimate used to study alternate RNA decoding. It can vary across substitutions, proteins, tissues and individuals because it reflects both the synthesis rate of each proteoform and its degradation rate.[1]
Measurement Considerations¶
- Differences in peptide ionization or detectability can bias a raw intensity ratio; paired-peptide comparisons and independent detectability checks help assess this risk.
- A substitution that changes protease cleavage probability can alter the observed peptide forms. The source study excluded base peptides also found in longer miscleaved peptides.
- Missing low-abundance peptides limit which pairs can be quantified and may bias distributions for low-abundance proteins.
- Agreement with shared peptides and estimates from independent protease digests provides supporting validation but does not remove every identification ambiguity.[1]