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Isovar support compatibility

Vaxrank requires Isovar 1.42.1 through 1.44.x. That release corrects flanking insertions/deletions in the anchored RNA candidate matcher. The fusion adapter still consumes and validates isovar.fusion_rna.v3; compatibility is tested with both the minimum 1.42.1 release and 1.44.2. Isovar 1.45 requires Osteosarc 0.15, while Vaxrank and Topiary currently share the 0.14 window; the coordinated update is tracked in #571.

Counts and candidate scores

Vaxrank's direct mutation fragments retain the following distinct measurements:

Fields Meaning
n_alt_reads, n_alt_fragments All alternate-supporting reads/fragments at the focal locus
n_alt_reads_supporting_protein_sequence, n_alt_fragments_supporting_protein_sequence Reads/fragments used to assemble the translated cDNA
n_rna_supporting_protein_sequence Assembly fragment count when available, otherwise assembly read count

Partial assembly reads need not span a full vaccine peptide. Fragment identity is scoped by SAM read group, rather than a QNAME alone. These counts are not independent molecule counts, TPM or cancer-cell fractions.

Isovar's separately enabled partial_read_support export reconsiders original reads against a specified RNA/protein hypothesis catalog. One scored fragment contributes one unit split across compatible hypotheses. The resulting fractional_fragments is a catalog-relative evidence score, not a raw count. Shorter local hypotheses remain alternatives and can change that allocation.

The corrected anchored_edit_compatibility.v2 matcher charges internal flanking indels once and treats unobserved distal overhangs as free. It conservatively reports coverage across tied alignments. Its tolerance is an explicit compatibility rule, not a calibrated error probability. See the producer's partial-read support contract and matching specification.

Ranking and provenance

This adoption changes no frozen openvax-v1 formula or selection golden. Vaxrank continues to consume Isovar's assembly-support counts and ordering; it does not enable fractional allocation or substitute those scores into RNA counts. Fusion admission still requires its own tumor-specificity evidence.

New direct fragments store the actual runtime Isovar version as sequence_source_version, carried into mixed-input evidence and native replay. An older fragment without this field retains an unknown version. Historical fixture producer versions remain immutable and are never rewritten to the current installation.