This is the 2D counterpart to the 3D ribosome scene, built around the exact same frame-shift arithmetic but drawn the way a molecular geneticist actually reasons about it: as a dose-response curve, a mod-3 phase clock, and a piano-roll codon track, instead of a spatial ribosome model.
frame shift Δ = ( Σ bases removed ) mod 3
Δ = 0 → in frame → translation runs to the end
Δ = 1,2 → frameshift → premature stop, no protein
ASO skipping efficiency(dose) = 1 / ( 1 + e^-((dose − EC50)/k) )
EC50 = 45% of max dose, k = 12 (illustrative dose–response sigmoid)
The two clock dials plot Δ directly as an angle: each dial has 3 ticks at 0°, 120°, 240° (one per residue of the mod-3 register), and the needle points straight up only when Δ = 0. Turn the ASO dose up and the "+ skip 51" needle jumps between ticks the instant the sigmoid crosses 50% — the same discrete arithmetic the 3D scene shows as a ribosome either running to the end of the track or hitting a red stop flag, just plotted as rotation instead of position.
The piano-roll strip below is the mature-mRNA codon track for the "typical" transcript at the current dose (blue = in-frame protein codon, red = nonsense codon read before a premature stop, dim = never reached); a read head sweeps across it at the translation-speed setting and a growing bead chain underneath is the resulting polypeptide. The grid at the bottom is an independent Monte-Carlo draw of a transcript population: each cell privately decides whether ASO worked on that molecule with probability = the current efficiency, then reruns the exact same Δ formula for that draw — green if it lands in frame, gray if not.
- Genotype buttons — set which dystrophin exons are genomically deleted in this patient.
- ASO dose — raises the fraction of transcripts in which exon 51 is successfully skipped, moving the dot along the sigmoid curve.
- Translation speed — how fast the read head sweeps the codon track.
- Resample population — redraws a fresh stochastic Monte-Carlo outcome for every cell in the grid, using the current dose's skipping probability.
Exon lengths are the same representative values for the human dystrophin exon 43–55 hotspot region used by the 3D scene, chosen to reproduce the correct real reading-frame outcome for each genotype shown; the underlying frame-arithmetic and dose–response model are the same ones used to design and prescribe real splice-switching ASO drugs (eteplirsen → exon 51, golodirsen/viltolarsen → exon 53, casimersen → exon 45).