assign_compartments gap-fill: reliable flux-based fill, not cobra's MILP - #82
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edkerk wants to merge 2 commits into
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assign_compartments gap-fill: reliable flux-based fill, not cobra's MILP#82edkerk wants to merge 2 commits into
edkerk wants to merge 2 commits into
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…atch Harden the flux-based _gapfill (universal-DB fill in localization.certify): operate on a model copy so the caller's model is never mutated; add candidates in one batch (per-reaction adds are super-linear at scale); return the flux-carrying set sorted, so the result does not depend on which co-optimal vertex the solver picked; and warn when most universal candidates share no metabolite id with the model, so a namespace mismatch is distinguishable from a genuine empty fill instead of returning [] silently. Knockout-recovery 60/60 (exact reaction each time) and 12/12 on realistic incomplete drafts, vs cobra's 45% and 0/12.
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The universal-DB gap-fill in
assign_compartmentsusedcobra.flux_analysis.gapfill, whose indicator MILP is unreliable at genome scale. This replaces it with a plain flux-based fill.The problem (measured)
cobra's
GapFillerMILP fails to find a valid gap-fill in the majority of genome-scale cases even when the exact reaction that restores growth is present in the universal:validate()correctly rejects the broken incumbent and raises.validate()gives identical results) and not a universal-size issue (a minimal 1-reaction universal fails identically) — the MILP itself is the ceiling.The fix
On a working copy of the model: add the universal candidates, hold biomass at the growth floor, run pFBA, and keep the added reactions that carry flux. A plain LP — it cannot have the MILP's failure mode, so a returned set always actually restores growth. The caller still re-certifies with a real FBA, so no false certificate is possible.
The set is flux-parsimonious (pFBA minimises total flux) and returned sorted, so it does not depend on which co-optimal vertex the solver lands on. It is not guaranteed reaction-count-minimal; the caller re-certifies regardless.
Result (measured, fixed reproducible knockout sample)
gapfill(before)Namespace safety
Candidates are matched to the model by metabolite id (as cobra's gapfill required) — the universal must share the draft's metabolite namespace. A candidate whose ids don't resolve becomes a dead-end that can't carry flux and is left out. Previously that produced a silent
[]; now, when most candidates fail to resolve,_gapfillwarns, so "found nothing" is distinguishable from "wrong namespace".Tests
Existing gap-fill tests pass unchanged; new direct
_gapfilltests cover the growth-restoring set, the empty-universal case, and the namespace-mismatch warning. Full suite green; ruff and mypy clean.Note
The assignment-ablation study in #75 documents the old 45% ceiling. This fix supersedes that framing — its gap-fill section should be updated to the reliable pFBA fill when #75 merges.