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BRENDA: filter implausible SA-derived kcats; default top_origin_limit 6 -> 4 - #58
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…eraction Investigates every difference between the June-2026 ecYeastGEM build and mainline geckopy today: matcher bug fixes, standard-kcat scope, OKP tiering, BRENDA 2026.1, and prediction source (CatPred/DLKcat/EITLEM). Six changes tune to the same place as June within noise; DLKcat and EITLEM both improve on it. BRENDA 2026.1 breaks tuning outright via a specific-activity/molecular-weight data trap (EC 2.3.1.297), traced to a mouse row surviving a dropped yeast row in the SA-MW join. Two mitigations compared (top_origin_limit=4, and a relative floor on derived kcats); the floor alone gives the best results for three of four predictors but breaks DLKcat via a Crabtree-effect/overflow mismatch, traced by comparing per-condition simulated vs measured ethanol secretion. Combining both mitigations is clean for every predictor tested.
c3_fl4 vs c3_o4 differ in only 34 of 4834 kcats; b26_fl4 vs b26_o4 are byte-identical. Not a bug: top_origin_limit=4 already demotes every origin-5/6 BRENDA match below any prediction, and CatPred's coverage is broad enough that almost every such reaction already has a CatPred prediction to fall back to. The floor only has room to matter where a predictor's coverage is patchier (DLKcat, EITLEM).
Two changes, meant to ship together (see docs/internal/pipeline_deltas_since_june.md): - load_brenda_data gains filter_outlier_kcats (default True): drops a kcat more than 4 orders of magnitude below the median of its own EC family (widening to a broader EC prefix when fewer than 5 reference values are available), computed from the union of the plain-kcat and SA-derived tables. Catches cases like EC 2.3.1.297, where the only molecular-weight row available is for the wrong organism and the resulting SA x MW join gives a kcat 8 orders of magnitude below a same-EC measurement that has no MW row and would otherwise be silently dropped instead of used. - merge_kcats' and merge_dlkcat_and_fuzzy_kcats' top_origin_limit default changes from 6 to 4, so a specific-activity-derived BRENDA match (origin 5-6) no longer automatically outranks a prediction. Redundant with the filter above when a predictor's coverage is broad (e.g. CatPred), but still needed on its own where coverage is patchier (DLKcat, EITLEM) -- see the doc for the Crabtree-effect mismatch this prevents when paired with the floor alone. Both changes are opt-out (filter_outlier_kcats=False, top_origin_limit=6 explicit) rather than removed, so the pre-existing behaviour stays reachable. Full test suite passes (1435 passed, 1 xfailed, 0 failed); added dedicated tests for the floor filter and updated the one test whose name and assertion encoded the old top_origin_limit default as intentional behaviour.
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This was referenced Sep 23, 2026
Investigation notes, not part of the public change.
This was referenced Oct 17, 2026
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BRENDA's specific-activity x molecular-weight join can produce a kcat many orders of magnitude below anything else reported for the same EC -- almost always a unit/transcription error upstream, not a real slow enzyme. Case in point: EC 2.3.1.297's only molecular-weight row is for a different organism than its lowest specific-activity row; the derived kcat (~4e-7 1/s) is 8 orders of magnitude below a same-EC yeast measurement that has no matching MW row and gets silently dropped instead. Once assigned, a kcat that small makes the enzyme-usage coefficient enormous and can make a model untunable (CMA-ES distance 4.19 vs 0.80 for an otherwise-identical model).
Two changes, meant to ship together:
load_brenda_datagainsfilter_outlier_kcats(defaultTrue): drops a kcat more than 4 orders of magnitude below the median of its own EC family, widening to a broader EC prefix when fewer than 5 reference values are available. The reference pool is the union of the plain kcat table and the SA-derived table, built once from the unfiltered tables.merge_kcats's (andmerge_dlkcat_and_fuzzy_kcats's)top_origin_limitdefault changes from 6 to 4, so a specific-activity-derived match no longer automatically outranks a prediction. Mostly redundant with the filter when a predictor's coverage is broad, but still needed where it's patchier -- pairing the filter with the old default on a DLKcat-predicted model instead reproduces a different failure (systematic under-prediction of the Crabtree/overflow response at high growth rate).Both are opt-out, not removed (
filter_outlier_kcats=False,top_origin_limit=6).Validation: re-ran the kcat-assignment-through-tuning pipeline on the June-2026 ecYeastGEM build and on mainline today, isolating each change (screen + CMA-ES, top-112 free parameters, 3 seeds, budget 6800). These two changes take an otherwise-broken model back to June's level or better. Write-up:
docs/internal/pipeline_deltas_since_june.md.Full test suite passes unchanged (1435 passed, 1 xfailed, 0 failed); added tests for the new filter and updated the one test whose assertion encoded the old default.