Cleavage-boundary processing models

Boundary inputs

Does sequence context spanning the two peptide boundaries add antigen-processing signal after controlling for peptide–MHC binding affinity, and can an explicit boundary-aligned architecture recover that signal more reliably than the legacy full-sequence convolution?

The boundary inputs intentionally contain residues on both sides of each cut, using standard protease cleavage-site orientation. The supported window variants are:

  • Compact N: n_flank[-5:] + peptide[:2] (P5...P1 | P1'P2')

  • Compact C: peptide[-2:] + c_flank[:5] (P2P1 | P1'...P5')

  • Extended N: n_flank[-5:] + peptide[:5] (P5...P1 | P1'...P5')

  • Extended C: peptide[-5:] + c_flank[:5] (P5...P1 | P1'...P5')

The phrase “flank branch” must not be used for this transform because the within-peptide residues are part of the cleavage context.

Unavailable external context is encoded with the existing X unknown token. This covers source-protein termini and prediction calls without supplied flanks. During training only, independently replace the complete five-residue external N or C segment with X with a configurable probability. Within-peptide residues are preserved. This context dropout is distinct from hidden unit/channel dropout and must be recorded separately.

Architecture and evaluation

The opt-in boundary architecture retains a full-peptide base path and adds two separate boundary-aligned residual paths. Each residual path receives its crossed-boundary window. Its contribution to the final logit is initialized to zero, so initial predictions come from the base path. See Release training recipe for the 5x5 boundary family selected for 2.3.0.

For processing-specific comparisons, use the same sample/length/affinity-matched risk sets for all predictors and retain the frozen public affinity reference. mhcflurry eval processing-flank-ablation can compare real, masked and shuffled contexts with unchanged weights. These diagnostics differ from end-to-end presentation ranking and do not establish that independently selected flank/no-flank ensembles constitute a controlled ablation.

Preserve input and model hashes, row identities, matching assignments, seeds and per-patient predictions. Report AP, PPV@N and AUROC with paired patient intervals, and evaluate the complete presentation model separately before promoting a processing change.