fix: reformulate SAM synthesis GPR and remove non-catalytic MAT2B#1030
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edkerk wants to merge 3 commits into
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fix: reformulate SAM synthesis GPR and remove non-catalytic MAT2B#1030edkerk wants to merge 3 commits into
edkerk wants to merge 3 commits into
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MAR03875 (SAM synthesis) and MAR07139 (SeAdoMet synthesis) had the GPR "MAT2B or MAT1A or MAT2A", which incorrectly lets MAT2B catalyse the reaction on its own. MAT2B (ENSG00000038274) is a non-catalytic regulatory subunit: it stabilises MAT2A and lowers the Km for methionine and the Ki for SAM, but its knockout leaves cellular SAM levels unchanged while only MAT2A depletion reduces SAM (PMID:39353892). MAT2A forms a catalytically active homotetramer without MAT2B and is the catalytic subunit; MAT1A is the catalytic isozyme. Set both GPRs to "ENSG00000151224 or ENSG00000168906" (MAT1A or MAT2A). MAT2B was associated only with these two reactions, so it is removed from the gene list.
Bring the branch up to date with develop (120 commits behind). Clean merge, no conflicts. Verified the branch's intent survives the merge: MAT2B (ENSG00000038274) is absent from genes.tsv, the YAML gene list and every GPR, and both SAM-synthesis reactions (EC 2.5.1.6) carry the reformulated two-gene rule (ENSG00000151224 or ENSG00000168906). genes.tsv rows and YAML gene entries match.
Model quality report
Each check name links to its explanation in the testResults README. Model checksDuplicate keys (model unloadable) and no growth block the merge; every other row is a non-blocking report.
MACAW and mass/charge balance
Model file and metabolic tasks
MEMOTETotal score: 63.2% (core subset) 0
Per-test scores
Full suite: 64.2% 0 · from the last The score above is the fast core subset. Comment Gene essentiality (Hart 2015)Not run automatically (it takes hours). Comment ❌ = a count rose vs the target branch (regression) · Full workflow run · this comment is edited as results come in |
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Main improvements in this PR:
As reported in #1013, the GPR of MAR03875 (SAM synthesis) and MAR07139 (SeAdoMet synthesis) was
MAT2B or MAT1A or MAT2A, which incorrectly lets the non-catalytic regulatory subunit MAT2B catalyse the reaction on its own.ENSG00000151224 or ENSG00000168906(MAT1A or MAT2A).ENSG00000038274) from the model, as it is non-catalytic and was associated only with these two reactions.MAT2B knockout leaves cellular SAM levels unchanged while only MAT2A depletion reduces SAM (PMID:39353892), and MAT2A forms a catalytically active homotetramer without MAT2B, so MAT2B should not gate flux. This differs from the reporter's
MAT1A OR (MAT2A AND MAT2B), which would make MAT2B falsely essential for the MAT2 route.I hereby confirm that I have:
developas a target branch