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Analysisestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.Q109-serine-one-carbon

Q109 enumeration: the ten panel members that got no entry, the measurement that declined each, the papers read and not used, and four identifier traps measured on this panel

A record of everything this beat looked at and did not write up, with the number that decided each case. Without it a later cycle cannot tell what was considered and rejected from what nobody ever checked.

The same thing, for a scientist

The Q109 panel declared **41 symbols** before any expression value was read. **Eleven got entries** (PHGDH, PSAT1, PSPH, SHMT2, MTHFD1, MTHFD2, ALDH1L2, CBS, CTH, GPT2, plus the analysis, hypothesis and experiment nodes). **Ten panel members were declined and each decline is recorded here with the measurement that justified it** [E1], because this project has no mechanism for distinguishing a considered rejection from an unexamined gap and `ana-literature-recall` has measured the cost. Also recorded: **eleven papers found, judged on-beat by title, and not used**; **four identifier traps measured on this panel**, of which one is a third instance of rule 62 and one is a collision the registry does not carry; and **two instrument defects found in this project's own tooling** - the rule-88 registry-grep command in `docs/QUEEN_BRIEF.md` returns `[]` for every symbol because the file is a dict, and a panel-maximum DepMap payload guard cannot see a single gene's empty payload (POLR2A returned 0 screens with its symbol readback passing).

Go deeper
The ten declines, each with its number
declinedthe measurement that declined it
GLSRS4;11 d7 VTP -0.06, EPZ +0.31, baseline 6.84 detected; MOLM13 -0.02; MV4;11 -0.54; all eight GPL570 probes within 0.49 in all three lines. DepMap -0.1803 (10.1%). GLS[tiab] = 6,986 records, fusion-scoped 0 with a non-empty translation and warninglist: ["No items found."]. A glutaminase that does not move is not part of this beat's biology whatever its standing in cancer metabolism.
SHMT1Moves in the wrong direction: VTP +0.78, EPZ +1.05, baseline 3.02; all four array probes within 0.37 in all three lines. Recorded inside gene-shmt2 as the paralogue observation, where it is load-bearing, rather than given an entry whose content would be one sign.
MTHFD2LBaseline 2.23 log2 CPM in RS4;11 and 1.05 in MOLM13, at or near the 1.0 floor; all seven array probes flat. Not measurable here. UniProt Q9H903's mitochondrial assignment is ECO:0000250 BY SIMILARITY to a rat protein - the weakest localisation record in the panel.
SLC1A5VTP -0.99, below the pre-declared 1.0 threshold by 0.01. Excluded by rule, and the rule was declared before the value was seen. Its MV4;11 value (-1.61) is larger, so a different line would have included it - recorded so the arbitrariness is visible.
SLC7A11VTP +0.13 - and it is the only DOT1L-SELECTIVE gene in 41, EPZ -1.84, margin +1.96, baseline 7.04 detected. Anomalous and unexplained; recorded as an anomaly in the analysis entry's instrument_facts rather than written up as biology. It is the cystine/glutamate antiporter immediately downstream of the transsulfuration arm, so it is not a random gene to behave oddly.
SLC3A2 / SLC7A5-1.26 and -1.34, margins -0.33 and -0.19 - i.e. on the compound-INDEPENDENT side. With SLC1A5 and SLC7A11 excluded the transport arm has n=2 and cannot be compared; no transporter entry written.
MTR / MTHFR / DHFR / TYMSDeclared as CONTEXT genes, not verdict genes. All flat (MTR +0.46, MTHFR -0.05, DHFR +0.29) or at the floor (TYMS RS4;11 baseline 0.00). Their DepMap profiles are the interesting part and are in the results file: the one-carbon SINKS are pan-essential (MAT2A -1.3510 / 95.2%, DHFR -0.8234 / 69.8%, TYMS -0.7992 / 51.2%) while the SOURCES are not - which is a finding, and it belongs to gene-mthfd1, where it is recorded.
ASNSAlready has an entry (gene-asns). Re-measured here: VTP -1.72, EPZ -1.47, margin -0.25, 86% reproduced - on the compound-INDEPENDENT side. That is a correction to the standing asparaginase hypothesis's reading and is reported rather than written into that entry.
ATF4 / DDIT3 / CHAC1 / TRIB3 / ATF5All have entries from the cycle-58 ISR beat and served here as the comparator arm. No new entries; their margins (-0.09 to +0.10) are the control against which the serine arm is judged.
MEIS1 / MEF2C / PBX3 / HOXA9 / HOXA10Positive control only. HOXA9 excluded from the control because it produced all 8 floor collisions in this run - log2FC exactly minus its baseline, with DMSO baselines of exactly 0.00 in RS4;11 day 2, MOLM13 day 2 and MOLM13 day 7. This is the third dataset in which HOXA9 has been unmeasurable in this project.
Papers found, judged on-beat by title, and NOT used

Recorded because a reader would reasonably expect them to be cited 2. None was read beyond its title and bibliographic record; each is a bounded rejection, not a bounded absence, and each says what would change the decision.

identifierone-line reasonwhat would change my mind
35385727 NADPH metabolism determines the leukemogenic capacity and drug resistance of AML cells (Cell Rep 2022)the ONLY fusion-scoped MTHFD1 record, and MTHFD1 is NADPH-coupledread it - the likeliest place for an existing MTHFD1 measurement in leukaemia
40328743 m6A/IGF2BP3-driven serine biosynthesis fuels AML stemness and metabolic vulnerability (Nat Commun 2025)serine biosynthesis in AML driven by IGF2BP3, and this graph holds gene-igf2bp3; myeloid, not the index diseaseread it - it may already contain the leukaemia PHGDH/PSAT1 dependency measurement gene-phgdh calls missing
36306790 The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in AML (Cancer Cell 2022)glutamine feeds the glutamate pool GPT2 transaminates; one of only two GPT2 leukaemia recordsread it
41151299 Targeting serine metabolism vulnerability in omipalisib-resistant AML with PHGDH inhibitors (Biomed Pharmacother 2025)a PHGDH-inhibitor result in leukaemia, in a resistance context unrelated to meninread it - the most recent PHGDH-inhibitor-in-leukaemia paper found
33357456 High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid Leukemic Cells (Cell Metab 2021)a nutrient-driven serine programme in AML, directly relevant to this beat's unrecorded-medium caveatread it
40462988 Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML (bioRxiv 2025)preprint; used as counter-evidence in gene-psat1 but NOT readpeer review, or reading it
40752747 The ALDH2-PKC-delta-SHMT2 axis regulates metabolic plasticity to promote leukaemia stem cell self-renewal (Cancer Lett 2025)SHMT2 in AML leukaemia stem cells; title onlyread it
42397900 A targetable FTO/SLC7A11/CBS/CTH axis controls cysteine metabolism, growth and survival in NSCLC (Sci Adv 2026)names three panel genes including the anomalous SLC7A11; lung cancerread it - the only paper treating CBS, CTH and SLC7A11 as one axis
41759595 Sodium aescinate induces renal cell ferroptosis through the ATF4/CTH/SQOR axis (Biochem Pharmacol 2026)the only published ATF4-CTH link; renal, pharmacologicalread it
42304489 and 41764940 ALDH1L2 in renal cell carcinoma organoids and in small cell lung cancerboth make ALDH1L2 ferroptosis-suppressing and therapy-resistance-promoting, OPPOSITE to the pancreatic result cited in gene-aldh1l2read either; ALDH1L2's direction in cancer is genuinely contested
39579612 Ailanthone targets the KMT2A-MEN1 complex to suppress lung metastasis of osteosarcoma (Phytomedicine 2025)one of only two menin-scoped PHGDH records; osteosarcomaread it

Laboratories publishing repeatedly in this area and cited nowhere in this beat: the Rabinowitz and Vander Heiden one-carbon flux groups (no KMT2A work found), and the de Koning / Van Schaftingen serine-deficiency clinical group, whose disorder papers were verified bibliographically and used only through UniProt's curated summaries.

Four identifier traps measured on this panel, and two defects in our own tooling

1. SERA is a 135,340-record false synonym of PHGDH with ZERO id overlap. PHGDH[tiab] = 665 with 4 fusion-scoped; SERA[tiab] = 135,340 with 26 fusion-scoped, intersecting PHGDH's four in zero ids. SERA is the UniProt entry-name stem, the plural of serum, and a word in several languages. Excluded, not unioned - the NUMA1/NMP22 rule. Reporting the union would have inflated the PHGDH-in-KMT2A literature from 1 relevant record to 27. PGDH3 = 6, 3PGDH = 34, both 0 fusion-scoped.

2. CBS fusion-scoped returns 3 and ALL THREE ARE FALSE POSITIVES, two of them from this project's own vocabulary. PMID 12686606 matches CBs = Cajal bodies; PMID 35180428 matches CBSs = CTCF binding sites; PMID 30727486 is Phytophthora root rot of Pinus pinea. Genuine count: zero. CBS[tiab] = 11,871. data/symbol-collisions.json has no CBS row - reported for the coordinator to add, with these measurements.

3. gene_exact:CTH AND organism_id:9606 AND reviewed:true returns TWO reviewed records - P32929 (CGL_HUMAN, 405 aa, CTH) and Q96IQ7 (VSIG2_HUMAN, 327 aa, VSIG2, carrying CTH as a synonym). Third instance of rule 62 in this project after DDIT3 and SFN, and the only one where the same gene pair had already defeated a different instrument: the registry's existing CTH row describes the Ensembl endpoint returning VSIG2 first. Refinement proposed: a collision row should name the OBJECT PAIR and both accessions, not the instrument that failed. A row about Ensembl invites a reader to trust UniProt for the same symbol.

4. PSA, a UniProt-listed synonym of PSAT1, returns 51,994 records (prostate-specific antigen). Excluded. PSAT = 327 and EPIP = 62, both 0 fusion-scoped. This exclusion rests on the token's known referent and NOT on a measured id-set intersection, which is weaker than the SERA case and is flagged as such in gene-psat1.

Defect A, in this project's own brief. Rule 88 instructs a beat to grep the collision registry with:

python -c "import io,json;d=json.load(io.open('data/symbol-collisions.json',encoding='utf-8'));print([r for r in d if 'BACH1' in json.dumps(r)])"

data/symbol-collisions.json is a dict with keys _comment, generated, verified_against, collisions, non_gene_antigens. Iterating it yields those five key strings, so the comprehension searches five short strings and returns [] for every symbol, including BACH1, which does have a row. Verified this session: the documented command returns [] for BACH1 while d['collisions'] returns 1 match. The rows are in d['collisions'], of which there are 169. The rule that has been asked twice to prevent rediscovered collisions ships a command that can never find one.

Defect B, in this beat's own DepMap guard. The brief requires a payload guard keyed to the panel maximum clearing ~1,000 screens rather than a per-row floor, and that is correct for detecting a truncated payload: panel maximum 1,258, PASS. But POLR2A - included as the canonical pan-essential control - returned 0 tissue blocks and 0 screens with its symbol readback passing. A panel-maximum guard is blind to a single gene's empty payload. The script prints per-gene n_tissue_blocks and n_screens, so it was visible, but it did not fail. A panel-maximum guard needs a companion per-gene zero-screen check.

Facts and figures
scriptanalyses/q109-is-the-serine-collapse-downstream-of-atf4-or-parallel/run.py
resultsanalyses/q109-is-the-serine-collapse-downstream-of-atf4-or-parallel/results.json
preregistrationanalyses/q109-is-the-serine-collapse-downstream-of-atf4-or-parallel/panel-preregistration.json
depmap scriptanalyses/q109-serine-one-carbon-depmap-dependency/run.py
statusrun
panel declared41
shown for fusionNot applicable to an enumeration entry, and answered rather than omitted: the declines and identifier measurements here are properties of a gene panel and a set of databases, not of a fusion. The fusion-scoped counts recorded above are all against an eight-operand KMT2A-fusion set with each term separately tagged and every cytogenetic term quoted.
absence classmeasured-not-searched
absence class noteThe commonest reason a panel member had nothing written about it in this corpus was that no previous search space included it - the previous serine panel in this graph was inherited from an ATF4-concordance list. That is what a pre-registered panel declared from pathway anatomy fixes, and ALDH1L2 is the worked example.
entries written
[
  "gene-phgdh",
  "gene-psat1",
  "gene-psph",
  "gene-shmt2",
  "gene-mthfd1",
  "gene-mthfd2",
  "gene-aldh1l2",
  "gene-cbs",
  "gene-cth",
  "gene-gpt2"
]
declines with the measurement that justified them
{
  "GLS": "RS4;11 d7 VTP -0.06 / EPZ +0.31 from a detected baseline of 6.84; MOLM13 -0.02; MV4;11 -0.54; all eight GPL570 probes within 0.49 in all three lines; DepMap mean -0.1803, 10.1% below -0.5; GLS[tiab] = 6,986 with a correctly formed fusion-scoped zero (non-empty translation, warninglist 'No items found.')",
  "SHMT1": "wrong direction - VTP +0.78, EPZ +1.05, baseline 3.02; all four array probes within 0.37 in all three lines; recorded inside gene-shmt2 as the paralogue observation where it is load-bearing",
  "MTHFD2L": "baseline 2.23 log2 CPM in RS4;11 and 1.05 in MOLM13, at or near the 1.0 floor; all seven array probes flat; UniProt Q9H903's mitochondrial assignment is ECO:0000250 BY SIMILARITY to a rat protein",
  "SLC1A5": "VTP -0.99, below the pre-declared 1.0 threshold by 0.01 - and its MV4;11 value is -1.61, so a different line would have included it. The arbitrariness is recorded rather than smoothed.",
  "SLC7A11": "VTP +0.13 / EPZ -1.84, margin +1.96, detected baseline 7.04 - the ONLY DOT1L-selective gene in 41. Declined by the |VTP| rule and flagged in the analysis entry as an anomaly, which is the weakest decline in this list.",
  "SLC3A2": "-1.26 with margin -0.33, on the compound-independent side; with SLC1A5 and SLC7A11 excluded the transport arm is n=2 and cannot be compared",
  "SLC7A5": "-1.34 with margin -0.19, same",
  "MTR_MTHFR_DHFR_TYMS": "declared as CONTEXT genes, not verdict genes; MTR +0.46, MTHFR -0.05, DHFR +0.29, TYMS baseline exactly 0.00. Their DepMap profiles are the finding and are recorded in gene-mthfd1: the one-carbon SINKS are pan-essential (MAT2A 95.2%, DHFR 69.8%, TYMS 51.2%) and the SOURCES are not.",
  "ASNS": "already has an entry. Re-measured: VTP -1.72, EPZ -1.47, margin -0.25, 86% reproduced - on the compound-INDEPENDENT side, which corrects how the standing asparaginase hypothesis should be read. Reported, not edited.",
  "ATF4_DDIT3_CHAC1_TRIB3_ATF5": "all have cycle-58 entries and served as the comparator arm; margins -0.085 to +0.095",
  "HOXA9": "excluded from the positive control - all 8 floor collisions in this run are HOXA9, with DMSO baselines of exactly 0.00 in RS4;11 day 2, MOLM13 day 2 and MOLM13 day 7, and -0.763 against a baseline of exactly 0.763 at RS4;11 day 7. Third dataset in this project in which HOXA9 has been unmeasurable."
}
papers found judged on beat and not used
{
  "33357456": "High Fructose Drives the Serine Synthesis Pathway in AML Cells (Cell Metab 2021) - directly relevant to this beat's unrecorded-medium caveat; unread",
  "35385727": "NADPH metabolism determines the leukemogenic capacity and drug resistance of AML cells (Cell Rep 2022) - the only fusion-scoped MTHFD1 record; unread",
  "36306790": "The m6A reader IGF2BP2 regulates glutamine metabolism in AML (Cancer Cell 2022) - one of two GPT2 leukaemia records; unread",
  "39579612": "Ailanthone targets the KMT2A-MEN1 complex in osteosarcoma (Phytomedicine 2025) - one of two menin-scoped PHGDH records; unread",
  "40328743": "m6A/IGF2BP3-driven serine biosynthesis fuels AML stemness and metabolic vulnerability (Nat Commun 2025) - may already contain the leukaemia PHGDH/PSAT1 dependency measurement gene-phgdh calls missing; unread",
  "40462988": "Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML (bioRxiv 2025) - cited as counter-evidence in gene-psat1 while unread",
  "40752747": "The ALDH2-PKC-delta-SHMT2 axis and leukaemia stem cell self-renewal (Cancer Lett 2025); unread",
  "41151299": "Targeting serine metabolism vulnerability in omipalisib-resistant AML with PHGDH inhibitors (Biomed Pharmacother 2025); unread",
  "41759595": "Sodium aescinate induces renal cell ferroptosis through the ATF4/CTH/SQOR axis (Biochem Pharmacol 2026) - the only published ATF4-CTH link; unread",
  "42397900": "A targetable FTO/SLC7A11/CBS/CTH axis in NSCLC (Sci Adv 2026) - the only paper treating CBS, CTH and SLC7A11 as one axis; unread",
  "42304489_and_41764940": "ALDH1L2 in renal cell carcinoma organoids and small cell lung cancer - both make ALDH1L2 ferroptosis-suppressing and resistance-promoting, opposite to the pancreatic result cited in gene-aldh1l2; unread",
  "laboratories_publishing_here_and_not_cited": "the Rabinowitz and Vander Heiden one-carbon flux groups (no KMT2A work found) and the de Koning / Van Schaftingen serine-deficiency clinical group, whose disorder papers were verified bibliographically and used only through UniProt's curated summaries"
}
identifier traps measured
{
  "PHGDH_SERA": {
    "PHGDH[tiab]": 665,
    "fusion_scoped": 4,
    "SERA[tiab]": 135340,
    "SERA_fusion_scoped": 26,
    "id_set_intersection": 0,
    "verdict": "EXCLUDE, not union - a synonym with zero overlap names a different object; SERA is the UniProt entry-name stem and the plural of serum",
    "PGDH3[tiab]": 6,
    "3PGDH[tiab]": 34
  },
  "CBS": {
    "CBS[tiab]": 11871,
    "fusion_scoped_raw": 3,
    "fusion_scoped_genuine": 0,
    "false_positives": {
      "12686606": "CBs = Cajal bodies",
      "30727486": "Phytophthora root rot of Pinus pinea",
      "35180428": "CBSs = CTCF binding sites"
    },
    "registry_row_exists": false,
    "note": "two of the three contaminants are core vocabulary of THIS project's own subject area; reported for the coordinator to add a row"
  },
  "CTH_VSIG2": {
    "uniprot_gene_exact_reviewed_rows": 2,
    "P32929": "CGL_HUMAN, 405 aa, gene_primary CTH",
    "Q96IQ7": "VSIG2_HUMAN, 327 aa, gene_primary VSIG2, synonyms CTH and CTXL",
    "ensembl_first_hit": "ENSG00000019102 = VSIG2; correct ENSG00000116761",
    "rule_62_instance": 3,
    "previous_instances": [
      "DDIT3",
      "SFN"
    ],
    "registry_row_exists": true,
    "registry_row_describes": "the ENSEMBL failure only",
    "refinement_proposed": "a collision row should name the OBJECT PAIR and both accessions, not the instrument that happened to fail"
  },
  "PSAT1_PSA": {
    "PSAT1[tiab]": 352,
    "PSA[tiab]": 51994,
    "PSAT[tiab]": 327,
    "EPIP[tiab]": 62,
    "verdict": "EXCLUDE PSA (prostate-specific antigen), but on the token's known referent and NOT on a measured id-set intersection - the weak form, flagged in gene-psat1"
  }
}
defects found in this projects own tooling
{
  "rule_88_registry_grep_command_returns_empty_for_every_symbol": "docs/QUEEN_BRIEF.md rule 88 prints `[r for r in d if 'BACH1' in json.dumps(r)]` over data/symbol-collisions.json. The file is a DICT with keys _comment, generated, verified_against, collisions, non_gene_antigens, so iterating it yields five key strings and the comprehension returns [] for every symbol. Verified this session: the documented command returns [] for BACH1 while d['collisions'] returns 1 match. The 169 rows live under d['collisions']. The rule written to stop beats rediscovering collisions ships a command whose failure mode is a FALSE CLEAR.",
  "correct_form": "python -c \"import io,json;d=json.load(io.open('data/symbol-collisions.json',encoding='utf-8'));print([r for r in d['collisions'] if 'BACH1' in json.dumps(r)])\"",
  "panel_maximum_depmap_guard_is_blind_to_a_single_empty_payload": "The brief requires a payload guard keyed to the panel MAXIMUM clearing ~1,000 screens rather than a per-row floor, which is right for detecting truncation and was PASS here at 1,258. But POLR2A - the canonical pan-essential control - returned 0 tissue blocks and 0 screens with its approvedSymbol readback PASSING. A panel-maximum guard cannot see a single gene's empty payload. The script prints per-gene n_tissue_blocks and n_screens so it was visible, but it did not fail. A companion per-gene zero-screen check is needed."
}
corrections to entries this beat does not own
{
  "ana-the-serine-arm-replicates-in-a-third-aff1-line-from-another-lab-but-the-stress-output-genes-do-not": "its data.did_not_replicate_the_isr_output lists CTH as '+0.24 against -1.57 in RS4;11'. CTH's MV4;11 Safe3 DMSO baseline is 0.29 log2 CPM, BELOW a 1.0 log2 CPM floor - an absence of signal, not a non-replication. CTH could not be tested in MV4;11. The source that settles it is that entry's own results.json, read from disk 2026-09-22. Also worth noting in the same block: DDIT3 (1.93), CHAC1 (1.90) and TRIB3 (3.00) are all near the floor in MV4;11, so the 'ISR did not replicate' conclusion is partly a detection question too.",
  "hyp-menin-inhibition-collapses-the-serine-asns-programme-and-should-resensitise-kmt2a-r-all-to-asparaginase": "ASNS's compound margin is -0.25 with 86% of the effect reproduced by EPZ5676, so ASNS is on the compound-INDEPENDENT side of the split this beat measures. The asparaginase prediction therefore does not inherit any menin-selectivity, and the entry should say so. No citation beyond this beat's own results.json is needed because the entry's own numbers are consistent with it - what is missing there is the EPZ5676 column.",
  "ana-does-atf4s-own-transcript-move-under-a-menin-inhibitor": "its data block lists PHGDH '-3.24 / -1.52' inside the_discriminating_arm alongside MEIS1, MEF2C and PBX3. That row is correct and is, in retrospect, the single most consequential number in that entry - it is the observation this whole beat is built on, and it appears there as an unremarked fourth item in a list of menin targets. Suggested change: promote it to prose, because a reader of that entry cannot currently tell that a serine-pathway gene is sitting in the menin-discriminating arm."
}
How this could bite us back
  • An enumeration entry is where a beat's negatives go to be forgotten. The test is whether someone re-running this beat next year would repeat the search AND the decision, or only the search - and the weakest item here by that test is SLC7A11, declined on a threshold rule with its anomaly recorded only in another entry's instrument-facts block.
  • Eleven papers were rejected on their titles alone and two of them were then cited as counter-evidence inside entries. Citing an unread paper against your own claim looks like intellectual honesty and is partly a way of appearing to have considered something.
Still open
  1. Should SLC7A11 have its own entry? It is the only DOT1L-selective gene in 41, with a margin of +1.96 from a detected baseline, it sits immediately downstream of the transsulfuration arm, and it was declined by a threshold rule designed for flat genes. This is the decline most likely to be wrong.
  2. Does PMID 40328743 already contain the leukaemia PHGDH/PSAT1 dependency measurement that gene-phgdh describes as missing? It is an m6A/IGF2BP3-driven serine-biosynthesis paper in AML and it was left unread. If it does, gene-phgdh's open question closes and its DepMap-versus-literature tension sharpens.
  3. How many other beats got a false clear from the rule-88 command? The defect returns [] for every symbol, which reads as 'no row exists', and the rule's own stated purpose is to stop collisions being rediscovered. A corpus-wide check of which beats reported a 'new' identifier trap that already had a row would measure the cost.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset

    Of 41 pre-registered panel symbols, ten were declined with a recorded measurement: GLS (RS4;11 d7 VTP -0.06, EPZ +0.31 from a detected baseline of 6.84, MOLM13 -0.02, all eight GPL570 probes within 0.49 in all three lines, DepMap -0.1803); SHMT1 (VTP +0.78, EPZ +1.05, wrong direction, baseline 3.02); MTHFD2L (baseline 2.23 in RS4;11 and 1.05 in MOLM13, at or near the floor); SLC1A5 (VTP -0.99, below the pre-declared 1.0 threshold); SLC7A11 (VTP +0.13 against EPZ -1.84, margin +1.96, the only DOT1L-selective gene in 41); SLC3A2 and SLC7A5 (margins -0.33 and -0.19, on the compound-independent side, leaving the transport arm at n=2); and MTR, MTHFR, DHFR and TYMS declared as context genes and all flat or at the floor, with TYMS's RS4;11 baseline exactly 0.00. HOXA9 was excluded from the menin-target positive control because it produced all 8 floor collisions in the run, with DMSO baselines of exactly 0.00 in three of four line/day combinations.

    What this evidence cannot show

    The 1.0 log2 inclusion threshold and the 6.0 log2 RMA / 1.0 log2 CPM detection floors were declared in advance but are conventions: SLC1A5 was declined at -0.99 and would have been included at a threshold of 0.95, and its MV4;11 value is -1.61, so a different line would have included it. That arbitrariness is recorded rather than smoothed over. Several declines rest on one line's transcript measurement and would not survive a different dataset - they are declines for THIS beat, not verdicts on the genes.

    Evidence that argues against this (1)
    • SLC7A11's exclusion is the one most likely to be wrong. It is the only gene in 41 with an inverted compound-selectivity (+0.13 under the menin inhibitor, -1.84 under the DOT1L inhibitor, margin +1.96 from a detected baseline), it sits immediately downstream of the transsulfuration arm this beat measured, and a published axis links FTO, SLC7A11, CBS and CTH as one cysteine-metabolism module. Declining it on a |VTP| threshold discards the panel's single most anomalous result on a rule designed for uninteresting flat genes. Kuganesan N et al. 2026
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Eleven papers were found, judged on-beat from their titles and bibliographic records, and not used: PMIDs 35385727, 40328743, 36306790, 41151299, 33357456, 40462988, 40752747, 42397900, 41759595, 42304489/41764940 and 39579612. Each was verified to exist through esummary with title, journal, year, author list and DOI read back, and none was read beyond its title.

    What this evidence cannot show

    A title-level judgement is the weakest form of rejection and several of these could overturn statements in this beat's entries - PMID 40328743 in particular may already contain the leukaemia PHGDH/PSAT1 dependency measurement that gene-phgdh describes as missing. The list is not exhaustive: it records the papers a reader would expect to see cited, not every abstract screened.

    Evidence that argues against this (1)
    • Two of these eleven were used as counter-evidence inside entries while being unread beyond their titles (40462988 in gene-psat1, 42304489 in gene-aldh1l2). Citing an unread paper as a counter-argument is weaker than citing it as support would be, because the counter-argument's force depends on content the citing entry has not seen - and this project's own standard is to mark such items and not paraphrase what they probably say. this repository 2026
  3. E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Four identifier traps were measured on this panel: PHGDH's synonym SERA returns 135,340 records with 26 fusion-scoped that intersect PHGDH's 4 in ZERO ids; CBS's three fusion-scoped records are all false positives (Cajal bodies, CTCF binding sites, and a Phytophthora plant-pathology paper), giving a genuine count of zero against a token total of 11,871; gene_exact:CTH AND organism_id:9606 AND reviewed:true returns TWO reviewed records, P32929 (CTH, 405 aa) and Q96IQ7 (VSIG2, 327 aa, carrying CTH as a synonym), a third instance of rule 62 after DDIT3 and SFN; and PSAT1's UniProt-listed synonym PSA returns 51,994 records of prostate-specific antigen. Separately, the rule-88 registry-grep command printed in docs/QUEEN_BRIEF.md returns [] for every symbol because data/symbol-collisions.json is a dict whose 169 rows live under the 'collisions' key - verified this session by running the documented command on BACH1, which returns [] while d['collisions'] returns one match.

    What this evidence cannot show

    The SERA exclusion rests on a measured zero id-set intersection over the first 200 records of each query, which is the strong form; the PSA exclusion rests on the token's known referent and NOT on a measured intersection, which is the weak form and is flagged as such in gene-psat1. The CBS false positives were established by opening three titles; the remaining 11,868 records were not screened, so a genuine CBS-in-KMT2A paper could exist whose abstract does not carry the fusion operands. The rule-88 defect is a fact about the documented command, not about the registry, which is well-formed and has 169 rows.

    Evidence that argues against this (1)
    • The rule-88 defect did not harm this beat, because the registry was read by loading the file and inspecting its structure rather than by running the documented one-liner - which is what happens when a beat reads the data instead of the instruction. That makes the defect invisible to anyone who follows the rule correctly and gets an empty result, which they would read as 'no row exists'. The failure mode is a false clear, and rule 88's whole purpose is to prevent rediscovered collisions. this repository 2026
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