Proteogenomics cross-references three layers of the same biological information: the genome (DNA sequence), the transcriptome (mRNA) and the proteome (peptides measured by mass spectrometry). A somatic point mutation in a coding exon changes one DNA base, which changes the mRNA codon, which can change the translated amino acid — a candidate neoantigen if the resulting peptide is presented on MHC class I.
DNA codon --T→U--> mRNA codon --genetic code--> amino acid
mass(peptide) = Σ residue_mass(aa_i) + 18.01056 (water, Da)
ΔMHC_score = clamp( 50 + 10·[KD(mut) − KD(wt)], 0, 100 )
neoantigen = (aa_mut ≠ aa_wt) AND (aa_mut ≠ stop) AND (ΔMHC_score ≥ threshold)
- Mutated codon — picks which of the 20 codons in the model gene carries the substitution.
- Substituted base — sets the new middle-position nucleotide, driving real codon-table translation.
- MHC threshold — the affinity score a variant peptide must clear to count as "presented" (using a Kyte–Doolittle hydropathy proxy for binding groove affinity).
- Flow speed / Play-Pause — controls the animated transcription → translation → presentation particle flow.
In cancer immunotherapy pipelines, exactly this kind of DNA→RNA→peptide→MS integration is used to prioritise tumour-specific neoantigens for personalised vaccine design.